Professor Brett Graham
Professor
School of Biomedical Sciences and Pharmacy (Anatomy)
- Email:brett.graham@newcastle.edu.au
- Phone:(02) 4921 5397
Pinpointing the pathways of pain
A fascination with the messages relayed via the spinal cord has maintained Associate Professor Brett Graham’s focus since he graduated with his PhD from UON in 2006. Ten years on, Brett’s research-focus remains intense, with the goal of mapping the nerve cells involved in pain signalling to allow for better treatment.
“This was my first passion in science, and I’ve been lucky enough that for the past 16 years I’ve been able to keep building on and pursuing that passion,” Brett says.
The spinal cord is a complex conductor of messaging from the body to the brain, but Brett has a simple analogy to explain the transmission of messages, and why it’s such a complicated field to research. “The spinal cord is like an international telephone exchange, with lots of calls arriving, in many different languages. The messages come in to the spinal cord and there are populations of nerve cells that perform an initial stage of processing, much like telephone operators connect calls to the intended receivers, before these messages are sent to the brain. It’s only once the information is received by the brain that you acknowledge the pain,” Brett explains.
“In our research we are trying to understand the nerve cells that receive this information from the body and then how these cells are connected to each other. These properties shape what information goes to the brain. We know the connections can disrupted - think of a spinal cord injury where the connections are severed. In this situation we still have sensory signals generated on the body, but the brain doesn’t receive the messages so you don’t feel them.”
Brett’s interest in neuroscience was piqued early. “I studied an undergraduate degree at UON in biomedical science, so I was always into science. The first thing that got me focused on neuroscience was after my neighbour passed away from Motor Neurone Disease. This is a horrible disease that represents a rapid failure of part of the nervous system that controls our movements and takes peoples’ lives in their most productive years - but why and how? That started me thinking about neuroscience, and while I didn’t end up studying Motor Neurone Disease, it did get me to focus on the spinal cord.”
Brett’s research is aimed at understanding the complex relationships between pain and spinal cord signalling. “When signals become cross-wired, the channels that are bringing touch-signals start to excite the pain-related channels and so all of a sudden touch can cause pain. There are many different conditions – such as neuropathic pain which cause people to experience pain due to touch. Most of the work we’re doing is trying to understand the types of nerve cells and the types of channels that send and receive those messages. If we identify those nerve cells we can understand what is unique about them, what signals they are meant to receive, and what they connect to. Once we can understand that circuit, and how it normally works we can then work with models of chronic pain and injury to better understand how to restore normal processing and normal sensations.”
It's a numbers game
The difficulty with this type of research is that much of our understanding is in general terms - that is theoretical, and we know that a lot of pain drugs work in the spinal cord by changing the pain signalling. Despite this general understanding, we still don’t know the exact channels and circuits where many of these drugs act. “It’s a challenge of numbers: throughout the brain there are one hundred billion neurons and the spinal cord is organised into a series of segments that each receive signals from various parts of the body –each segment contains around 20 000 nerve cells that potentially deal with pain.”
“However, only about one nerve cell in every 100 will play the key role of transmitting information to the brain. All the other nerve cells are interconnected into local spinal circuits that adjust the level of pain signalling that is ultimately relayed to the brain. There’s a whole lot of scope to change the signal and therefore change the experience of pain.”
“Thankfully, we’re coming into a time when the techniques we can use to study these connections are circuits are rapidly advancing – and that’s one of the waves that we’re riding here at UON. What we really want to do is identify the different types of sensory nerve cells in the spinal cord, work out how they’re connected and what that means for pain messaging.”
“The challenge we’re dealing with is that, while chronic pain can be considered a disease in its own right, many other diseases and disorders also cause pain – such stroke, arthritis, multiple sclerosis and even cancer. Overall, the statistics say that approximately 1 in 5 people will experience chronic pain in one form or another, which is incredibly debilitating and impacts on all aspects of life.”
Modelling the nerve pathways
“What we’re in the business of is understanding the underlying issues behind what causes pain because it’s with this understanding we can look to develop better drugs. By identifying the nerve cells involved in signalling pain, we’ll be better able to develop drugs that can do that selectively.”
By using mouse modelling in their research, Brett and his team have risen to the challenge of mapping out the complex pathways of nerve cells. “We’re doing our research using transgenic mice, where new genes are introduced to give us a clearer view of things. For example, we use the genes for fluorescent proteins that come from deep-sea jellyfish, and that brings us the capacity to ‘light up’ and ‘label’ certain nerve pathways. By making specific types of nerve cells glow we can study them selectively.”
Otherwise, the challenge that you face is that when you go to record nerve cell signalling in the spinal cord you’ve got 20 000 potential pathways to choose from, so you need to do many, many recordings and see if any patterns emerge. Whereas with the green fluorescent proteins in transgenic mice, a subset of the nerve cells are glowing so you can start to get a signature of what their specific properties are like.”
Using this green fluorescent protein allows Brett and his team the ability to study these nerve cells and start to put together the components – effectively colour-coding the spinal pain circuits.
“We’re also using optogenetics which uses the gene for a different protein expressed in blue-green algae. It’s a really exciting technology that’s rapidly developed over the last five or six years. Optogenics was named Technique of the Year by Nature in 2010 and it’s being applied in research around the world. Essentially, the way the blue-green algae protein works is that when light shines on it, it excites the cell and this allows the algae to swims toward the light. By placing this gene in transgenic mice we can not only see specific nerve cells – we can turn them on using light.”
The reason people are so excited about doing that is that it helps us work out how nerve cells are connected into circuits. “This is allowing us to move rapidly toward understanding the principle pain circuits in the spinal cord. Our goal is to create a ‘map’ of these circuits and start to understand how disrupting them causes the symptoms of chronic pain. One of my PhD students is working on a population of interconnected ‘accelerator’ nerve cells and trying to understand how they might work to amplify pain. “The question we’re asking is ‘In Chronic pain is it the case that these ‘amplifers’ become switched on to enhance pain signalling and really rev everything up?’ That’s what we think is happening.”
“We are really excited about the potential role of these accelerator cells, but coming back to the fact that pain can result from many different diseases and conditions, we don’t think there is one pathway to chronic pain. We think there’s likely many different routes or populations of nerve cells that could become dysfunctional and it’s our long-term goal to understand all those potential routes to pain.
When it comes to treating pain a blanket approach that simply shuts down all spinal circuits doesn’t seem to work very well and typically brings with it a range of side effects. The best pain treatments are much more likely to come from more subtle and specific adjustments. For example, you might need to turn some circuits up and some circuits down.” Fortunately the transgenic studies that Brett and his team are using have them well placed to meet this challenge and continue pinpointing the many pathways to pain.
Pinpointing the pathways of pain
The primary theme of A Prof Graham's research is spinal sensory coding.
Career Summary
Biography
Brett Graham graduated with his PhD in 2006 and after a short postdoctoral period started his research laboratory, now the Spinal Cord Connections Group, in 2008. The primary theme of his research is spinal sensory coding, a topic he has been focused on since completing Honours year studying inhibitory synaptic transmission between spinal dorsal horn neurons in 2001.
Qualifications
- Doctor of Philosophy, University of Newcastle
- Bachelor of Biomedical Sciences, University of Newcastle
- Bachelor of Biomedical Sciences (Hons), University of Newcastle
Keywords
- Biomedical Science
- Neurophysiology
- Neuroscience
- Pain
- Spinal cord
- Synaptic transmission
Fields of Research
Code | Description | Percentage |
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300902 | Veterinary anatomy and physiology | 100 |
Professional Experience
UON Appointment
Title | Organisation / Department |
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Professor | University of Newcastle School of Biomedical Sciences and Pharmacy Australia |
Academic appointment
Dates | Title | Organisation / Department |
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1/1/2008 - 1/12/2011 | Fellow | NHMRC (National Health & Medical Research Council) |
Membership
Dates | Title | Organisation / Department |
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1/1/2001 - | Membership - Australian Neuroscience Society (ANS) | Australian Neuroscience Society (ANS) Australia |
1/1/2001 - | Membership - International Association for the Study of Pain (IASP) | IASP International Association for the Study of Pain |
Publications
For publications that are currently unpublished or in-press, details are shown in italics.
Chapter (3 outputs)
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2022 |
Smith KM, Graham BA, 'Channelrhodopsin-2 Assisted Circuit Mapping in the Spinal Cord Dorsal Horn', Contemporary Approaches to the Study of Pain. From Molecules to Neural Networks, Springer Nature, New York, NY 347-373 (2022) [B1]
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2012 |
Graham BA, Callister RJ, 'Pain', The Mouse Nervous System, Academic Press, San Diego 589-606 (2012) [B1]
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2011 |
Graham B, Callister R, 'Pain', The Mouse Nervous System 589-606 (2011) This chapter provides an overview of the current understanding of pain processing mechanisms with emphasis on the contributions made by the mouse. The application of molecular gen... [more] This chapter provides an overview of the current understanding of pain processing mechanisms with emphasis on the contributions made by the mouse. The application of molecular genetics to pain research has provided great insights into mechanisms underlying the complex sensory experience called "pain." In broad terms, pain research using mice can be divided into three areas: work on naïve or normal animals aimed at increasing the understanding of pain processing mechanisms; work using mouse models of experimentally-induced pain where the goal is to uncover mechanisms that drive or amplify pain responses; and work where genetically modified mice are used to explore the role of various proteins or neuron types in pain processing mechanisms and circuits. Knockout and transgenic mice have been used to firmly establish the identity and understand the role of key proteins involved in transmitting information about noxious stimuli from the periphery into the spinal cord, and via the ascending pain pathway to the cerebral cortex. In the periphery, studies have identified a variety of sensors involved in detecting specific types of noxious stimuli, the second messenger pathways involved in sensitizing nociceptors in certain inflammatory and neuropathic pain models, and the identity and role of certain sodium channels that are largely confined to the transmission of information about tissue damage. In the CNS, particularly the dorsal horn of the spinal cord, genetically modified mice have allowed the study of specific genetically tagged neuron types, and helped in building better models of spinal cord pain circuits.
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Journal article (67 outputs)
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2024 |
Russo MA, Santarelli DM, Austin PJ, Graham BA, 'Progressing into a new paradigm: how we must leave the past behind if we want a change in pain research outcomes', PAIN MEDICINE, 25 5-7 (2024)
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2024 |
Mitchell CS, Campbell EJ, Fisher SD, Stanton LM, Burton NJ, Pearl AJ, et al., 'Optogenetic recruitment of hypothalamic corticotrophin-releasing-hormone (CRH) neurons reduces motivational drive.', Transl Psychiatry, 14 8 (2024) [C1]
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2023 |
Davis OC, Dickie AC, Mustapa MB, Boyle KA, Browne TJ, Gradwell MA, et al., 'Calretinin-expressing islet cells: a source of pre- and post-synaptic inhibition of non-peptidergic nociceptor input to the mouse spinal cord.', bioRxiv, (2023)
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2023 |
Russo MA, Volschenk W, Bailey D, Santarelli DM, Holliday E, Barker D, et al., 'A Novel, Paresthesia-Free Spinal Cord Stimulation Waveform for Chronic Neuropathic Low Back Pain: Six-Month Results of a Prospective, Single-Arm, Dose-Response Study.', Neuromodulation : journal of the International Neuromodulation Society, 26 1412-1423 (2023) [C1]
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2023 |
Russo M, Graham B, Santarelli DM, 'Gabapentin-Friend or foe?', Pain practice : the official journal of World Institute of Pain, 23 63-69 (2023) [C1]
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2023 |
Davis OC, Dickie AC, Mustapa MB, Boyle KA, Browne TJ, Gradwell MA, et al., 'Calretinin-expressing islet cells are a source of pre- and post-synaptic inhibition of non-peptidergic nociceptor input to the mouse spinal cord.', Scientific reports, 13 11561 (2023) [C1]
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2022 |
Gradwell MA, Boyle KA, Browne TJ, Bell AM, Leonardo J, Reyes FSP, et al., 'Diversity of inhibitory and excitatory parvalbumin interneuron circuits in the dorsal horn', PAIN, 163 E432-E452 (2022) [C1]
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2022 |
Iredale JA, Stoddard JG, Drury HR, Browne TJ, Elton A, Madden JF, et al., 'Recording Network Activity in Spinal Nociceptive Circuits using Microelectrode Arrays', JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, (2022) [C1]
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2022 |
Gradwell MA, Smith KM, Dayas CV, Smith DW, Hughes DI, Callister RJ, Graham BA, 'Altered Intrinsic Properties and Inhibitory Connectivity in Aged Parvalbumin-Expressing Dorsal Horn Neurons', FRONTIERS IN NEURAL CIRCUITS, 16 (2022) [C1]
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2021 |
Browne TJ, Smith KM, Gradwell MA, Iredale JA, Dayas CV, Callister RJ, et al., 'Spinoparabrachial projection neurons form distinct classes in the mouse dorsal horn', PAIN, 162 1977-1994 (2021) [C1]
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2020 |
Madden JF, Davis OC, Boyle KA, Iredale JA, Browne TJ, Callister RJ, et al., 'Functional and Molecular Analysis of Proprioceptive Sensory Neuron Excitability in Mice', Frontiers in Molecular Neuroscience, 13 1-13 (2020) [C1]
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2020 |
Callister RJ, Brichta AM, Schaefer AT, Graham BA, Stuart DG, 'Pioneers in CNS inhibition: 2. Charles Sherrington and John Eccles on inhibition in spinal and supraspinal structures', BRAIN RESEARCH, 1734 (2020) [C1]
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2020 |
Gradwell MA, Callister RJ, Graham BA, 'Reviewing the case for compromised spinal inhibition in neuropathic pain', Journal of Neural Transmission, 127 481-503 (2020) [C1] A striking and debilitating property of the nervous system is that damage to this tissue can cause chronic intractable pain, which persists long after resolution of the initial in... [more] A striking and debilitating property of the nervous system is that damage to this tissue can cause chronic intractable pain, which persists long after resolution of the initial insult. This neuropathic form of pain can arise from trauma to peripheral nerves, the spinal cord, or brain. It can also result from neuropathies associated with disease states such as diabetes, human immunodeficiency virus/AIDS, herpes, multiple sclerosis, cancer, and chemotherapy. Regardless of the origin, treatments for neuropathic pain remain inadequate. This continues to drive research into the underlying mechanisms. While the literature shows that dysfunction in numerous loci throughout the CNS can contribute to chronic pain, the spinal cord and in particular inhibitory signalling in this region have remained major research areas. This review focuses on local spinal inhibition provided by dorsal horn interneurons, and how such inhibition is disrupted during the development and maintenance of neuropathic pain.
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2020 |
Browne TJ, Hughes DI, Dayas CV, Callister RJ, Graham BA, 'Projection Neuron Axon Collaterals in the Dorsal Horn: Placing a New Player in Spinal Cord Pain Processing', FRONTIERS IN PHYSIOLOGY, 11 (2020) [C1]
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2020 |
Mayhew JA, Cummins MJ, Cresswell ET, Callister RJ, Smith DW, Graham BA, 'Age-related gene expression changes in lumbar spinal cord: Implications for neuropathic pain', Molecular Pain, 16 (2020) [C1] Clinically, pain has an uneven incidence throughout lifespan and impacts more on the elderly. In contrast, preclinical models of pathological pain have typically used juvenile or ... [more] Clinically, pain has an uneven incidence throughout lifespan and impacts more on the elderly. In contrast, preclinical models of pathological pain have typically used juvenile or young adult animals to highlight the involvement of glial populations, proinflammatory cytokines, and chemokines in the onset and maintenance of pathological signalling in the spinal dorsal horn. The potential impact of this mismatch is also complicated by the growing appreciation that the aged central nervous system exists in a state of chronic inflammation because of enhanced proinflammatory cytokine/chemokine signalling and glial activation. To address this issue, we investigated the impact of aging on the expression of genes that have been associated with neuropathic pain, glial signalling, neurotransmission and neuroinflammation. We used qRT-PCR to quantify gene expression and focussed on the dorsal horn of the spinal cord as this is an important perturbation site in neuropathic pain. To control for global vs region-specific age-related changes in gene expression, the ventral half of the spinal cord was examined. Our results show that expression of proinflammatory chemokines, pattern recognition receptors, and neurotransmitter system components was significantly altered in aged (24¿32 months) versus young mice (2¿4 months). Notably, the magnitude and direction of these changes were spinal-cord region dependent. For example, expression of the chemokine, Cxcl13, increased 119-fold in dorsal spinal cord, but only 2-fold in the ventral spinal cord of old versus young mice. Therefore, we propose the dorsal spinal cord of old animals is subject to region-specific alterations that prime circuits for the development of pathological pain, potentially in the absence of the peripheral triggers normally associated with these conditions.
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2020 |
Browne TJ, Gradwell MA, Iredale JA, Maden JF, Callister RJ, Hughes DI, et al., 'Transgenic Cross-Referencing of Inhibitory and Excitatory Interneuron Populations to Dissect Neuronal Heterogeneity in the Dorsal Horn', Frontiers in Molecular Neuroscience, 13 1-20 (2020) [C1]
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2019 |
Yeoh JW, James MH, Adams CD, Bains JS, Sakurai T, Aston-Jones G, et al., 'Activation of lateral hypothalamic group III metabotropic glutamate receptors suppresses cocaine-seeking following abstinence and normalizes drug-associated increases in excitatory drive to orexin/hypocretin cells', Neuropharmacology, 154 22-33 (2019) [C1] The perifornical/lateral hypothalamic area (LHA) orexin (hypocretin) system is involved in drug-seeking behavior elicited by drug-associated stimuli. Cocaine exposure is associate... [more] The perifornical/lateral hypothalamic area (LHA) orexin (hypocretin) system is involved in drug-seeking behavior elicited by drug-associated stimuli. Cocaine exposure is associated with presynaptic plasticity at LHA orexin cells such that excitatory input to orexin cells is enhanced acutely and into withdrawal. These changes may augment orexin cell reactivity to drug-related cues during abstinence and contribute to relapse-like behavior. Studies in hypothalamic slices from drug-naïve animals indicate that agonism of group III metabotropic glutamate receptors (mGluRs) reduces presynaptic glutamate release onto orexin cells. Therefore, we examined the group III mGluR system as a potential target to reduce orexin cell excitability in-vivo, including in animals with cocaine experience. First, we verified that group III mGluRs regulate orexin cell activity in behaving animals by showing that intra-LHA infusions of the selective agonist L-(+)-2-Amino-4-phosphonobutyric acid (L-AP4) reduces c-fos expression in orexin cells following 24 h food deprivation. Next, we extended these findings to show that intra-LHA L-AP4 infusions reduced discriminative stimulus-driven cocaine-seeking following withdrawal. Importantly, L-AP4 had no effect on lever pressing for sucrose pellets or general motoric behavior. Finally, using whole-cell patch-clamp recordings from identified orexin cells in orexin-GFP transgenic mice, we show enhanced presynaptic drive to orexin cells following 14d withdrawal and that this plasticity can be normalized by L-AP4. Together, these data indicate that activation of group III mGluRs in LHA reduces orexin cell activity in vivo and may be an effective strategy to suppress cocaine-seeking behavior following withdrawal. These effects are likely mediated, at least in part, by normalization of presynaptic plasticity at orexin cells that occurs as a result of cocaine exposure. This article is part of the Special Issue entitled ¿Hypothalamic Control of Homeostasis¿.
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2019 |
Mayhew JA, Callister RJ, Walker FR, Smith DW, Graham BA, 'Aging alters signaling properties in the mouse spinal dorsal horn', MOLECULAR PAIN, 15 (2019) [C1]
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2019 |
Boyle KA, Gradwell MA, Yasaka T, Dickie AC, Polgár E, Ganley RP, et al., 'Defining a Spinal Microcircuit that Gates Myelinated Afferent Input: Implications for Tactile Allodynia', Cell Reports, 28 526-540.e6 (2019) [C1] Chronic pain presents a major unmet clinical problem. The development of more effective treatments is hindered by our limited understanding of the neuronal circuits underlying sen... [more] Chronic pain presents a major unmet clinical problem. The development of more effective treatments is hindered by our limited understanding of the neuronal circuits underlying sensory perception. Here, we show that parvalbumin (PV)-expressing dorsal horn interneurons modulate the passage of sensory information conveyed by low-threshold mechanoreceptors (LTMRs) directly via presynaptic inhibition and also gate the polysynaptic relay of LTMR input to pain circuits by inhibiting lamina II excitatory interneurons whose axons project into lamina I. We show changes in the functional properties of these PV interneurons following peripheral nerve injury and that silencing these cells unmasks a circuit that allows innocuous touch inputs to activate pain circuits by increasing network activity in laminae I¿IV. Such changes are likely to result in the development of tactile allodynia and could be targeted for more effective treatment of mechanical pain. In this study, Boyle et al. identify parvalbumin-expressing spinal interneurons as a principal source of axoaxonic synapses onto cutaneous myelinated afferents and inhibitory inputs onto lamina II vertical cells. Following peripheral nerve injury, disinhibition of these targets facilitates the aberrant recruitment of pain circuits, leading to tactile allodynia.
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2019 |
Ip CK, Zhang L, Farzi A, Qi Y, Clarke I, Reed F, et al., 'Amygdala NPY Circuits Promote the Development of Accelerated Obesity under Chronic Stress Conditions', Cell Metabolism, 30 111-128.e6 (2019) [C1] Neuropeptide Y (NPY) exerts a powerful orexigenic effect in the hypothalamus. However, extra-hypothalamic nuclei also produce NPY, but its influence on energy homeostasis is uncle... [more] Neuropeptide Y (NPY) exerts a powerful orexigenic effect in the hypothalamus. However, extra-hypothalamic nuclei also produce NPY, but its influence on energy homeostasis is unclear. Here we uncover a previously unknown feeding stimulatory pathway that is activated under conditions of stress in combination with calorie-dense food; NPY neurons in the central amygdala are responsible for an exacerbated response to a combined stress and high-fat-diet intervention. Central amygdala NPY neuron-specific Npy overexpression mimics the obese phenotype seen in a combined stress and high-fat-diet model, which is prevented by the selective ablation of Npy. Using food intake and energy expenditure as readouts, we demonstrate that selective activation of central amygdala NPY neurons results in increased food intake and decreased energy expenditure. Mechanistically, it is the diminished insulin signaling capacity on central amygdala NPY neurons under combined stress and high-fat-diet conditions that leads to the exaggerated development of obesity.
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2019 |
Graham BA, Hughes DI, 'Rewards, perils and pitfalls of untangling spinal pain circuits', Current Opinion in Physiology, 11 35-41 (2019) [C1] Pain is a complex perception that is fundamental to our daily survival. Under normal circumstances, it serves an important protective function to guard against tissue damage or al... [more] Pain is a complex perception that is fundamental to our daily survival. Under normal circumstances, it serves an important protective function to guard against tissue damage or alert the body to dangerous environments. Under pathological states, however, the perception of pain can become chronic, maladaptive, resistant to treatment, and presents a serious clinical and societal problem. A wealth of literature suggests that disruption of sensory processing within the spinal cord contributes to chronic pain, but our limited understanding of spinal circuitry in health and disease remains a barrier to the development of new therapeutic strategies. The aim of this brief review is to outline current thinking about how individual components of functionally distinct spinal microcircuits can be identified and manipulated to determine their role in influencing our perception of pain in acute and chronic states.
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2019 |
Smith KM, Browne TJ, Davis OC, Coyle A, Boyle KA, Watanabe M, et al., 'Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn', ELIFE, 8 (2019) [C1]
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2018 |
Mayhew J, Graham BA, Biber K, Nilsson M, Walker FR, 'Purinergic modulation of glutamate transmission: An expanding role in stress-linked neuropathology.', Neuroscience and biobehavioral reviews, 93 26-37 (2018) [C1]
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2017 |
Gradwell MA, Boyle KA, Callister RJ, Hughes DI, Graham BA, 'Heteromeric a/ß glycine receptors regulate excitability in parvalbumin-expressing dorsal horn neurons through phasic and tonic glycinergic inhibition', Journal of Physiology, 595 7185-7202 (2017) [C1] Key points: Spinal parvalbumin-expressing interneurons have been identified as a critical source of inhibition to regulate sensory thresholds by gating mechanical inputs in the do... [more] Key points: Spinal parvalbumin-expressing interneurons have been identified as a critical source of inhibition to regulate sensory thresholds by gating mechanical inputs in the dorsal horn. This study assessed the inhibitory regulation of the parvalbumin-expressing interneurons, showing that synaptic and tonic glycinergic currents dominate, blocking neuronal or glial glycine transporters enhances tonic glycinergic currents, and these manipulations reduce excitability. Synaptically released glycine also enhanced tonic glycinergic currents and resulted in decreased parvalbumin-expressing interneuron excitability. Analysis of the glycine receptor properties mediating inhibition of parvalbumin neurons, as well as single channel recordings, indicates that heteromeric a/ß subunit-containing receptors underlie both synaptic and tonic glycinergic currents. Our findings indicate that glycinergic inhibition provides critical control of excitability in parvalbumin-expressing interneurons in the dorsal horn and represents a pharmacological target to manipulate spinal sensory processing. Abstract: The dorsal horn (DH) of the spinal cord is an important site for modality-specific processing of sensory information and is essential for contextually relevant sensory experience. Parvalbumin-expressing inhibitory interneurons (PV+ INs) have functional properties and connectivity that enables them to segregate tactile and nociceptive information. Here we examine inhibitory drive to PV+ INs using targeted patch-clamp recording in spinal cord slices from adult transgenic mice that express enhanced green fluorescent protein in PV+ INs. Analysis of inhibitory synaptic currents showed glycinergic transmission is the dominant form of phasic inhibition to PV+ INs. In addition, PV+ INs expressed robust glycine-mediated tonic currents; however, we found no evidence for tonic GABAergic currents. Manipulation of extracellular glycine by blocking either, or both, the glial and neuronal glycine transporters markedly decreased PV+ IN excitability, as assessed by action potential discharge. This decreased excitability was replicated when tonic glycinergic currents were increased by electrically activating glycinergic synapses. Finally, we show that both phasic and tonic forms of glycinergic inhibition are mediated by heteromeric a/ß glycine receptors. This differs from GABAA receptors in the dorsal horn, where different receptor stoichiometries underlie phasic and tonic inhibition. Together these data suggest both phasic and tonic glycinergic inhibition regulate the output of PV+ INs and contribute to the processing and segregation of tactile and nociceptive information. The shared stoichiometry for phasic and tonic glycine receptors suggests pharmacology is unlikely to be able to selectively target each form of inhibition in PV+ INs.
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2017 |
Farrell KE, Keely S, Walker MM, Brichta AM, Graham BA, Callister RJ, 'Altered intrinsic and synaptic properties of lumbosacral dorsal horn neurons in a mouse model of colitis', Neuroscience, 362 152-167 (2017) [C1] Visceral pain in inflammatory and functional gastrointestinal conditions is a major clinical problem. The exact mechanisms underlying the development of pain, during and after vis... [more] Visceral pain in inflammatory and functional gastrointestinal conditions is a major clinical problem. The exact mechanisms underlying the development of pain, during and after visceral inflammation are unknown. However, clinical and pre-clinical evidence suggests plasticity within the spinal cord dorsal horn is a contributing factor. Here we use an in vivo preparation and patch-clamp electrophysiology to test whether the synaptic and intrinsic properties of superficial dorsal horn (SDH) neurons are altered 5 days after the induction of mild colitis in adult male mice (i.e. during acute inflammation of the colon). Whole-cell recordings were made from lumbosacral (L6-S1) superficial dorsal horn neurons (SDH), in animals under isoflurane anesthesia. Noxious colorectal distension (CRD) was used to identify SDH neurons with colonic inputs, while stimulation of the hind paw and tail was employed to assess convergent cutaneous input. Following inflammation, a significantly increased proportion of SDH neurons received both colonic and cutaneous inputs, compared to neurons in naïve animals. In addition, the nature and magnitude of responses to CRD and cutaneous stimulation differed in inflamed animals, as was spontaneous excitatory synaptic drive. Conversely, several measures of intrinsic excitability were altered in a manner that would decrease SDH network excitability following colitis. We propose that during inflammation, sensitization of colonic afferents results in increased signaling to the SDH. This is accompanied by plasticity in SDH neurons whereby their intrinsic properties are changed to compensate for altered afferent activity.
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2017 |
Campbell EJ, Mitchell CS, Adams CD, Yeoh JW, Hodgson DM, Graham BA, Dayas CV, 'Chemogenetic activation of the lateral hypothalamus reverses early life stress-induced deficits in motivational drive', European Journal of Neuroscience, 46 2285-2296 (2017) [C1] Altered motivated behaviour is a cardinal feature of several neuropsychiatric conditions including mood disorders. One well-characterized antecedent to the development of mood dis... [more] Altered motivated behaviour is a cardinal feature of several neuropsychiatric conditions including mood disorders. One well-characterized antecedent to the development of mood disorders is exposure to early life stress (ELS). A key brain substrate controlling motivated behaviour is the lateral hypothalamus (LH). Here, we examined the effect of ELS on LH activation and the motivation to self-administer sucrose. We tested whether chemogenetic activation of LH circuits could modify sucrose responding in ELS rats and examined the impact on LH cell populations. Male rat pups were maternally separated for 0 or 3¿h on postnatal days 2¿14. During adolescence, rats received bilateral injections of hM3D(Gq), the excitatory designer receptor exclusively activated by designer drugs, into LH. In adulthood, rats were trained to self-administer sucrose and tested under a progressive ratio schedule to determine their motivation for reward following injection with either vehicle or 5¿mg/kg clozapine-N-oxide. Brains were processed for Fos-protein immunohistochemistry. ELS significantly suppressed lever responding for sucrose, indicating a long-lasting impact of ELS on motivation circuits. hM3D(Gq) activation of LH increased responding, normalizing deficits in ELS rats, and increased Fos-positive orexin and MCH cell numbers within LH. Our findings indicate that despite being susceptible to environmental stressors, LH circuits retain the capacity to overcome ELS-induced deficits in motivated behaviour.
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2017 |
Tae H-S, Smith KM, Phillips AM, Boyle KA, Li M, Forster IC, et al., 'Gabapentin Modulates HCN4 Channel Voltage-Dependence', FRONTIERS IN PHARMACOLOGY, 8 (2017) [C1]
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2017 |
Flynn JR, Conn VL, Boyle KA, Hughes DI, Watanabe M, Velasquez T, et al., 'Anatomical and Molecular Properties of Long Descending Propriospinal Neurons in Mice', FRONTIERS IN NEUROANATOMY, 11 (2017) [C1]
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2016 |
Duchatel RJ, Jobling P, Graham BA, Harms LR, Michie PT, Hodgson DM, Tooney PA, 'Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia', Progress in Neuro-Psychopharmacology and Biological Psychiatry, 65 118-126 (2016) [C1] Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) den... [more] Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN<sup>+</sup>) and somatostatin (SST<sup>+</sup>) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN<sup>+</sup> IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN<sup>+</sup> IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST<sup>+</sup> IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN<sup>+</sup> and SST<sup>+</sup> IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia.
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2016 |
Farrell KE, Rank MM, Keely S, Brichta AM, Graham BA, Callister RJ, 'In vivo characterization of colorectal and cutaneous inputs to lumbosacral dorsal horn neurons in the mouse spinal cord', Neuroscience, 316 13-25 (2016) [C1] Chronic abdominal pain is a common symptom of inflammatory bowel disease and often persists in the absence of gut inflammation. Although the mechanisms responsible for ongoing pai... [more] Chronic abdominal pain is a common symptom of inflammatory bowel disease and often persists in the absence of gut inflammation. Although the mechanisms responsible for ongoing pain are unknown, clinical and preclinical evidence suggests lumbosacral spinal cord dorsal horn neurons contribute to these symptoms. At present, we know little about the intrinsic and synaptic properties of this population of neurons in either normal or inflammed conditions. Therefore, we developed an in vivo preparation to make patch-clamp recordings from superficial dorsal horn (SDH) neurons receiving colonic inputs in naïve male mice. Recordings were made in the lumbosacral spinal cord (L6-S1) under isoflurane anesthesia. Noxious colorectal distension (CRD) was used to determine whether SDH neurons received inputs from mechanical stimulation/distension of the colon. Responses to hind paw/tail cutaneous stimulation and intrinsic and synaptic properties were also assessed, as well as action potential discharge properties. Approximately 11% of lumbosacral SDH neurons in the cohort of neurons sampled responded to CRD and a majority of these responses were subthreshold. Most CRD-responsive neurons (80%) also responded to cutaneous stimuli, compared with <50% of CRD-non-responsive neurons. Furthermore, CRD-responsive neurons had more hyperpolarized resting membrane potentials, larger rheobase currents, and reduced levels of excitatory drive, compared to CRD-non-responsive neurons. Our results demonstrate that CRD-responsive neurons can be distinguished from CRD-non-responsive neurons by several differences in their membrane properties and excitatory synaptic inputs. We also demonstrate that SDH neurons with colonic inputs show predominately subthreshold responses to CRD and exhibit a high degree of viscerosomatic convergence.
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2016 |
Smith KM, Boyle KA, Mustapa M, Jobling P, Callister RJ, Hughes DI, Graham BA, 'Distinct forms of synaptic inhibition and neuromodulation regulate calretinin-positive neuron excitability in the spinal cord dorsal horn', Neuroscience, 326 10-21 (2016) [C1] The dorsal horn (DH) of the spinal cord contains a heterogenous population of neurons that process incoming sensory signals before information ascends to the brain. We have recent... [more] The dorsal horn (DH) of the spinal cord contains a heterogenous population of neurons that process incoming sensory signals before information ascends to the brain. We have recently characterized calretinin-expressing (CR+) neurons in the DH and shown that they can be divided into excitatory and inhibitory subpopulations. The excitatory population receives high-frequency excitatory synaptic input and expresses delayed firing action potential discharge, whereas the inhibitory population receives weak excitatory drive and exhibits tonic or initial bursting discharge. Here, we characterize inhibitory synaptic input and neuromodulation in the two CR+ populations, in order to determine how each is regulated. We show that excitatory CR+ neurons receive mixed inhibition from GABAergic and glycinergic sources, whereas inhibitory CR+ neurons receive inhibition, which is dominated by glycine. Noradrenaline and serotonin produced robust outward currents in excitatory CR+ neurons, predicting an inhibitory action on these neurons, but neither neuromodulator produced a response in CR+ inhibitory neurons. In contrast, enkephalin (along with selective mu and delta opioid receptor agonists) produced outward currents in inhibitory CR+ neurons, consistent with an inhibitory action but did not affect the excitatory CR+ population. Our findings show that the pharmacology of inhibitory inputs and neuromodulator actions on CR+ cells, along with their excitatory inputs can define these two subpopulations further, and this could be exploited to modulate discrete aspects of sensory processing selectively in the DH.
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2015 |
Kongsui R, Johnson SJ, Graham BA, Nilsson M, Walker FR, 'A combined cumulative threshold spectra and digital reconstruction analysis reveal structural alterations of microglia within the prefrontal cortex following low-dose LPS administration', Neuroscience, 310 629-640 (2015) [C1] Sickness behaviors have become the focus of great interest in recent years as they represent a clear case of how peripheral disturbances in immune signaling can disrupt quite comp... [more] Sickness behaviors have become the focus of great interest in recent years as they represent a clear case of how peripheral disturbances in immune signaling can disrupt quite complex behaviors. In the current study, we were interested in examining whether we could identify any significant morphological disturbances in microglia associated with these sickness-like behaviors in adult male Sprague-Dawley rats. We chose lipopolysaccharide (LPS 100 µg/kg/i.p.), to induce sickness-like behaviors as it is the most well-validated approach to do so in rodents and humans. We were particularly interested in examining changes in microglia within the prefrontal cortex (PFC) as several recent neuroimaging studies have highlighted significant functional changes in this region following peripheral LPS administration. Paraformaldehyde-fixed tissue was collected from animals 24 h post LPS administration and labeled immunohistochemically with an antibody directed to bind to Iba-1, a protein known to be involved in the structural remodeling of microglia. To analyze changes, we have made use of two recently described image analysis procedures. The first is known as cumulative threshold spectra (CTS) analysis. The second involves the unsupervised digital reconstruction of microglia. We undertook these complementary analysis of microglial cells in the both the pre- and infralimbic divisions of the PFC. Our results indicated that microglial soma size was significantly enlarged, while cell processes had contracted slightly following LPS administration. To our knowledge this study is to first to definitely demonstrate substantial microglial disturbances within the PFC following LPS delivered at a dose that was sufficient to induce significant sickness-like behavior.
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2015 |
Callister RJ, Graham BA, 'Spicing up the gabapentionoids: Facilitating gabapentin entry in spinal pain circuits', Neuroscience Letters, 584 395-396 (2015) [C3]
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2015 |
Smith KM, Boyle KA, Madden JF, Dickinson SA, Jobling P, Callister RJ, et al., 'Functional heterogeneity of calretinin-expressing neurons in the mouse superficial dorsal horn: Implications for spinal pain processing', Journal of Physiology, 593 4319-4339 (2015) [C1] Neurons in the superficial dorsal horn (SDH) of the spinal cord play an important role in nociceptive, thermal, itch and light touch sensations. Excitatory interneurons comprise ~... [more] Neurons in the superficial dorsal horn (SDH) of the spinal cord play an important role in nociceptive, thermal, itch and light touch sensations. Excitatory interneurons comprise ~65% of all SDH neurons but surprisingly few studies have investigated their role in spinal sensory processing. Here we use a transgenic mouse to study putative excitatory SDH neurons that express the calcium binding protein calretinin (CR). Our immunocytochemical, morphological and electrophysiological analysis identified two distinct populations of CR-expressing neurons, which we termed 'Typical' and 'Atypical'. Typical CR-expressing neurons comprised ~85% of the population and exhibited characteristic excitatory interneuron properties including delayed firing discharge, large rapid A-type potassium currents, and central, radial or vertical cell morphologies. Atypical neurons exhibited properties consistent with inhibitory interneurons, including tonic firing or initial bursting discharge, Ih currents, and islet cell morphology. Although both Typical and Atypical CR-expressing neurons responded to noxious peripheral stimulation, the excitatory drive onto Typical CR-expressing neurons was much stronger. Furthermore, Atypical CR-expressing cells comprise at least two functionally distinct subpopulations based on their responsiveness to noxious peripheral stimulation and neurochemical profile. Together our data suggest CR expression is not restricted to excitatory neurons in the SDH. Under normal conditions, the contribution of 'Typical' excitatory CR-expressing neurons to overall SDH excitability may be limited by the presence of A-type potassium currents, which limit the effectiveness of their strong excitatory input. Their contribution may, however, be increased in pathological situations where A-type potassium currents are decreased. By contrast, 'Atypical' inhibitory neurons with their excitable phenotype but weak excitatory input may be more easily recruited during increased peripheral stimulation.
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2014 |
Tadros MA, Farrell KE, Schofield PR, Brichta AM, Graham BA, Fuglevand AJ, Callister RJ, 'Intrinsic and synaptic homeostatic plasticity in motoneurons from mice with glycine receptor mutations', Journal of Neurophysiology, 111 1487-1498 (2014) [C1] Inhibitory synaptic inputs to hypoglossal motoneurons (HMs) are important for modulating excitability in brainstem circuits. Here we ask whether reduced inhibition, as occurs in t... [more] Inhibitory synaptic inputs to hypoglossal motoneurons (HMs) are important for modulating excitability in brainstem circuits. Here we ask whether reduced inhibition, as occurs in three murine mutants with distinct naturally occurring mutations in the glycine receptor (GlyR), leads to intrinsic and/or synaptic homeostatic plasticity. Whole cell recordings were obtained from HMs in transverse brainstem slices from wild-type (wt), spasmodic (spd), spastic (spa), and oscillator (ot) mice (C57Bl/6, approximately postnatal day 21). Passive and action potential (AP) properties in spd and ot HMs were similar to wt. In contrast, spa HMs had lower input resistances, more depolarized resting membrane potentials, higher rheobase currents, smaller AP amplitudes, and slower afterhyperpolarization current decay times. The excitability of HMs, assessed by "gain" in injected current/firing-frequency plots, was similar in all strains whereas the incidence of rebound spiking was increased in spd. The difference between recruitment and derecruitment current (i.e., ¿I) for AP discharge during ramp current injection was more negative in spa and ot. GABAA miniature inhibitory postsynaptic current (mIPSC) amplitude was increased in spa and ot but not spd, suggesting diminished glycinergic drive leads to compensatory adjustments in the other major fast inhibitory synaptic transmitter system in these mutants. Overall, our data suggest long-term reduction in glycinergic drive to HMs results in changes in intrinsic and synaptic properties that are consistent with homeostatic plasticity in spa and ot but not in spd. We propose such plasticity is an attempt to stabilize HM output, which succeeds in spa but fails in ot. © 2014 the American Physiological Society.
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2014 |
Farrell KE, Keely S, Graham BA, Callister R, Callister RJ, 'A Systematic Review of the Evidence for Central Nervous System Plasticity in Animal Models of Inflammatory-mediated Gastrointestinal Pain', INFLAMMATORY BOWEL DISEASES, 20 176-195 (2014) [C1]
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2014 |
Yeoh JW, Campbell EJ, James MH, Graham BA, Dayas CV, 'Orexin antagonists for neuropsychiatric disease: progress and potential pitfalls.', Front Neurosci, 8 36 (2014) [C1]
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2014 |
Yeoh JW, James MH, Graham BA, Dayas CV, 'Electrophysiological characteristics of paraventricular thalamic (PVT) neurons in response to cocaine and cocaine- and amphetamine-regulated transcript (CART)', FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 8 (2014) [C1]
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2014 |
Harris BM, Hughes DI, Bolton PS, Tadros MA, Callister RJ, Graham BA, 'Contrasting alterations to synaptic and intrinsic properties in upper-cervical superficial dorsal horn neurons following acute neck muscle inflammation', MOLECULAR PAIN, 10 (2014) [C1]
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2014 |
Stuart DG, Schaefer AT, Massion J, Graham BA, Callister RJ, 'Pioneers in CNS inhibition: 1. Ivan M. Sechenov, the first to clearly demonstrate inhibition arising in the brain', Brain Research, 1548 20-48 (2014) [C1] This article reviews the contributions of Ivan Michailovich Sechenov [1829-1905] to the neurophysiological concept of central inhibition. He first studied this concept in the frog... [more] This article reviews the contributions of Ivan Michailovich Sechenov [1829-1905] to the neurophysiological concept of central inhibition. He first studied this concept in the frog and on himself. Later his trainees extended the study of central inhibition to other mammalian species. Outside his own country, Sechenov is better known for his prescient contributions to physiological psychology. In Russia, however, he is also revered as "the father of Russian physiology," because of his contributions to neurophysiology and other aspects of physiology including blood gases and respiration, the physiology and biomechanics of movement, and general physiology concepts that appeared in his textbooks and later works he helped translate from largely German sources. After graduation from Moscow University Medical School in 1856 he spent 31/2 years in Germany and Austria where he attended lectures and conducted research under the direction of several prominent physiologists and biochemists. In his subsequent academic career he held positions at universities in St. Petersburg (1860-1870; 1876-1888), Odessa (1871-1876) and Moscow (1890-1905). From 1860 onwards he was acclaimed as a physiologist in academic circles. He was also well known in Russian society for his public lectures on physiology and his views on physiological psychology. The latter resulted in him being branded "politically unreliable" by the tsarist bureaucracy from 1863 onwards. Sechenov's first (1862) study on central inhibition remains his most memorable. He delayed the withdrawal of a frog's foot from a weak acid solution by chemical or electrical stimulation of selected parts of the central nervous system. He also noted similar effects on his own hand during co-activation of other sensory inputs by tickling or teeth gnashing. © 2013 Elsevier B.V. All rights reserved.
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2014 |
Smith KM, Madden JF, Callister RJ, Hughes DI, Graham BA, 'The search for novel analgesics: re-examining spinal cord circuits with new tools.', Front Pharmacol, 5 22 (2014) [C1]
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2013 |
Hughes DI, Boyle KA, Kinnon CM, Bilsland C, Quayle JA, Callister RJ, Graham BA, 'HCN4 subunit expression in fast-spiking interneurons of the rat spinal cord and hippocampus', Neuroscience, 237 7-18 (2013) [C1] Hyperpolarisation-activated (Ih) currents are considered important for dendritic integration, synaptic transmission, setting membrane potential and rhythmic action potential (AP) ... [more] Hyperpolarisation-activated (Ih) currents are considered important for dendritic integration, synaptic transmission, setting membrane potential and rhythmic action potential (AP) discharge in neurons of the central nervous system. Hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels underlie these currents and are composed of homo- and hetero-tetramers of HCN channel subunits (HCN1-4), which confer distinct biophysical properties on the channel. Despite understanding the structure-function relationships of HCN channels with different subunit stoichiometry, our knowledge of their expression in defined neuronal populations remains limited. Recently, we have shown that HCN subunit expression is a feature of a specific population of dorsal horn interneurons that exhibit high-frequency AP discharge. Here we expand on this observation and use neuroanatomical markers to first identify well-characterised neuronal populations in the lumbar spinal cord and hippocampus and subsequently determine whether HCN4 expression correlates with high-frequency AP discharge in these populations. In the spinal cord, HCN4 is expressed in several putative inhibitory interneuron populations including parvalbumin (PV)-expressing islet cells (84.1%; SD: ±2.87), in addition to all putative Renshaw cells and Ia inhibitory interneurons. Similarly, virtually all PV-expressing cells in the hippocampal CA1 subfield (93.5%; ±3.40) and the dentate gyrus (90.9%; ±6.38) also express HCN4. This HCN4 expression profile in inhibitory interneurons mirrors both the prevalence of Ih sub-threshold currents and high-frequency AP discharge. Our findings indicate that HCN4 subunits are expressed in several populations of spinal and hippocampal interneurons, which are known to express both Ih sub-threshold currents and exhibit high-frequency AP discharge. As HCN channel function plays a critical role in pain perception, learning and memory, and sleep as well as the pathogenesis of several neurological diseases, these findings provide important insights into the identity and neurochemical status of cells that could underlie such conditions. © 2013 IBRO.
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2012 |
Tadros MA, Harris B, Anderson WB, Brichta AM, Graham BA, Callister RJ, 'Are all spinal segments equal: Intrinsic membrane properties of superficial dorsal horn neurons in the developing and mature mouse spinal cord', Journal of Physiology, 590 2409-2425 (2012) [C1]
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2012 |
Yeoh JW, James MH, Jobling P, Bains JS, Graham BA, Dayas CV, 'Cocaine potentiates excitatory drive in the perifornical/lateral hypothalamus', Journal of Physiology, 590 3677-3689 (2012) [C1]
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2012 |
Hughes DI, Sikander S, Kinnon CM, Boyle KA, Watanabe M, Callister RJ, Graham BA, 'Morphological, neurochemical and electrophysiological features of parvalbumin-expressing cells: A likely source of axo-axonic inputs in the mouse spinal dorsal horn', Journal of Physiology, 590 3927-3951 (2012) [C1]
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2011 |
Graham BA, Tadros MA, Schofield PR, Callister RJ, 'Probing glycine receptor stoichiometry in superficial dorsal horn neurones using the spasmodic mouse', Journal of Physiology, 589 2459-2474 (2011) [C1]
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2011 |
Flynn JR, Graham BA, Galea MP, Callister RJ, 'The role of propriospinal interneurons in recovery from spinal cord injury', Neuropharmacology, 60 809-822 (2011) [C1]
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2011 |
Flynn JR, Brichta AM, Galea MP, Callister RJ, Graham BA, 'A horizontal slice preparation for examining the functional connectivity of dorsal column fibres in mouse spinal cord', Journal of Neuroscience Methods, 200 113-120 (2011) [C1]
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2010 |
Callister RJ, Graham BA, 'Early history of glycine receptor biology in mammalian spinal cord circuits', Frontiers in Molecular Neuroscience, 3 1-13 (2010) [C1]
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2010 |
Jobling P, Graham BA, Brichta AM, Callister RJ, 'Cervix stimulation evokes predominantly subthreshold synaptic responses in mouse thoracolumbar and lumbosacral superficial dorsal horn neurons', Journal of Sexual Medicine, 7 2068-2076 (2010) [C1]
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2010 |
De Oliveira R, Graham BA, Howlett MC, Gravina FS, Oliveira MW, Imtiaz MS, et al., 'Ketamine anesthesia helps preserve neuronal viability', Journal of Neuroscience Methods, 189 230-232 (2010) [C1]
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2010 |
Graham BA, Clausen PD, Bolton PS, 'A descriptive study of the force and displacement profiles of the toggle-recoil spinal manipulative procedure (adjustment) as performed by chiropractors', Manual Therapy, 15 74-79 (2010) [C1]
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2009 |
Anderson WB, Graham BA, Beveridge NJ, Tooney PA, Brichta AM, Callister RJ, 'Different forms of glycine- and GABA(A)-receptor mediated inhibitory synaptic transmission in mouse superficial and deep dorsal horn neurons', Molecular Pain, 5 1-16 (2009) [C1]
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2009 |
Tadros MA, Graham BA, Brichta AM, Callister RJ, 'Evidence for a critical period in the development of excitability and potassium currents in mouse lumbar superficial dorsal horn neurons', Journal of Neurophysiology, 101 1800-1812 (2009) [C1]
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2008 |
Graham BA, Brichta AM, Callister RJ, 'Recording temperature affects the excitability of mouse superficial dorsal horn neurons, in vitro', Journal of Neurophysiology, 99 2048-2059 (2008) [C1]
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2007 |
Graham BA, Brichta AM, Callister RJ, 'Moving from an averaged to specific view of spinal cord pain processing circuits', Journal of Neurophysiology, 98 1057-1063 (2007) [C1]
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2007 |
Graham BA, Brichta AM, Callister RJ, 'Pinch-current injection defines two discharge profiles in mouse superficial dorsal horn neurones, in vitro', Journal of Physiology, 578 787-798 (2007) [C1]
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2007 |
Graham BA, Brichta AM, Schofield PR, Callister RJ, 'Altered potassium channel function in the superficial dorsal horn of the spastic mouse', Journal of Physiology, 584 121-136 (2007) [C1]
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2006 |
Graham BA, Schofield PR, Sah P, Margrie TW, Callister RJ, 'Distinct physiological mechanisms underlie altered glycinergic synaptic transmission in the murine mutants, spastic, spasmodic, and oscillator', Journal of Neuroscience, 26 4880-4890 (2006) [C1]
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2004 |
Graham BA, Brichta AM, Callister RJ, 'In vivo responses of mouse superficial dorsal horn neurones to both current injection and peripheral cutaneous stimulation', Journal of Physiology, 561.3 749-763 (2004) [C1]
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2004 |
Graham BA, Brichta AM, Callister RJ, 'An in vivo mouse spinal cord preparation for patch-clamp analysis of nociceptive processing', Journal of Neuroscience Methods, 136 221-228 (2004) [C1]
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2003 |
Graham BA, Schofield PR, Sah P, Callister RJ, 'Altered inhibitory synaptic transmission in superficial dorsal horn neurones in spastic and oscillator mice', The Journal of Physiology, 551.3 905-916 (2003) [C1]
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2002 |
Graham BA, Schofield P, Sah P, Callister RJ, 'GABAAergic and glycinergic synaptic transmission in superficial dorsal horn neurones of wild type, spastic and oscillator mice', Proceedings of the Australian Neuroscience Society, 22:94 n/a (2002) [C3]
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Show 64 more journal articles |
Conference (35 outputs)
Year | Citation | Altmetrics | Link | |||||
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2021 |
Katz-Barber M, Manning E, Fisher S, Bains J, Graham B, Dayas C, 'Emerging evidence of dysregulated stress reactivity in hypothalamic corticotrophin-releasing hormone (CRH) neurons following cocaine exposure', Online (2021)
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2021 |
Katz-Barber M, Manning E, Fisher S, Bains J, Graham B, Dayas C, 'Stress reactivity of hypothalamic corticotrophin-releasing hormone (CRH) neurons following cocaine exposure', Online (2021)
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2019 |
Katz-Barber M, Sherwood C, Mitchell C, Burton N, Fisher S, Bains J, et al., 'That's Stressful! Characterising the Neurobiology of Addiction', The Florey Institute of Neuroscience and Mental Health (2019)
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2015 |
Farrell K, Rank M, Keely S, Graham B, Callister R, 'In vivo electrophysiological characterisation of mouse lumbosacral dorsal horn neurons receiving visceral inputs', JOURNAL OF NEUROCHEMISTRY, Cairns, AUSTRALIA (2015) [E3]
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2015 | Gunnersen J, Lovric M, Teng K, Daykin H, Wright C, Barwood J, et al., 'SEZ6 binds the analgesic target alpha 2 delta and contributes to neuropathic pain plasticity', JOURNAL OF NEUROCHEMISTRY, Cairns, AUSTRALIA (2015) [E3] | |||||||
2015 |
Smith K, Dickinson S, Jobling P, Callister R, Graham B, 'Peripheral nerve injury alters the excitability of calretinin positive dorsal horn neurons', JOURNAL OF NEUROCHEMISTRY, Cairns, AUSTRALIA (2015) [E3]
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2015 |
Dickinson S, Smith K, Bigland M, Smith D, Jobling P, Graham B, 'Morphological analysis of microglial and astrocyte populations in the superficial dorsal horn of spinal cord in aged mice', JOURNAL OF NEUROCHEMISTRY, Cairns, AUSTRALIA (2015) [E3]
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2015 |
Duchatel R, Jobling P, Graham B, Harms L, Michie P, Hodgson D, Tooney P, 'Modelling white matter neuron pathology in schizophrenia using maternal immune activation', JOURNAL OF NEUROCHEMISTRY, Cairns, AUSTRALIA (2015) [E3]
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2015 |
Gradwell M, Callister R, Hughes D, Graham B, 'Optogenetic dissection of a parvalbumin interneuron microcircuits within the superficial dorsal horn of the spinal cord', JOURNAL OF NEUROCHEMISTRY, Cairns, AUSTRALIA (2015) [E3]
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2015 |
Graham B, Smith K, Madden J, Dickinson S, Bigland M, Jobling P, Smith D, 'Characteristics of dorsal horn neuron excitability and synaptic input in aged mice', JOURNAL OF NEUROCHEMISTRY, Cairns, AUSTRALIA (2015) [E3]
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2014 |
Farrell KE, Graham BA, Keely S, Callister RJ, 'Understanding the mechanisms underlying chronic pain in IBD: A new method for studying visceral inputs from the gastrointestinal tract', JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY (2014) [E3]
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2014 |
Wellings TP, Graham BA, Camp AJ, Callister RJ, Brichta AM, Lim R, 'Calcium binding proteins subdivide medial vestibular nucleus neurons', Journal of Vestibular Research: Equilibrium and Orientation: an international journal of experimental and clinical vestibular science, Buenos Aires, Argentina (2014) [E3]
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2012 |
Flynn JR, Callister RJ, Graham BA, 'Electrophysiological properties of identified long descending propriospinal neurons in mice', Abstracts. Australian Neuroscience Society 32nd Annual Meeting, Gold Coast, Queensland (2012) [E3]
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2012 |
Tadros MA, Lim R, Graham BA, Hughes DI, Brichta AM, Callister RJ, 'Excitability of human ventral horn neurons during early foetal development', Abstracts. Australian Neuroscience Society 32nd Annual Meeting, Gold Coast, Queensland (2012) [E3]
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2012 |
Jobling P, Madden JF, Graham BA, 'Whole cell patch clamp recordings from muscle spindle afferent neurons in intact dorsal root ganglia isolated from mouse', Abstracts. Australian Neuroscience Society 32nd Annual Meeting, Gold Coast, Queensland (2012) [E3]
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2012 |
Farrell KE, Keely S, Graham BA, Minahan KL, Madden JF, Callister RJ, 'Spinal cord signalling in a mouse model of inflammatory bowel disease', Journal of Gastroenterology and Hepatology, Adelaide, SA (2012) [E3]
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2011 |
Tadros MA, Lim R, Graham BA, Hughes DI, Brichta AM, Callister RJ, 'Excitability of human ventral horn neurons during early foetal development', Poster Abstracts. Australian Neuroscience Society Annual Meeting, Auckland, NZ (2011) [E3]
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2011 |
Jobling P, Smith K, Madden J, Hickey LR, Graham BA, 'Characterisation of pain behaviour, spinal neurochemistry and glial populations in a mouse antigen-induced arthritis model', Posters. Australian Neuroscience Society 31st Annual Meeting, Auckland, New Zealand (2011) [E3]
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2011 |
Graham BA, Sah P, Brichta AM, Callister RJ, Hughes DI, 'Neuroanatomical and neurochemical features of parvalbumin-expressing neurons in the mouse spinal dorsal horn', Posters. Australian Neuroscience Society 31st Annual Meeting, Auckland, New Zealand (2011) [E3]
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2010 |
Callister RJ, Walsh MA, Harris BM, Anderson WB, Brichta AM, Graham BA, 'Segmental and developmental differences in the excitability of mouse superficial dorsal horn neurons', 13th World Congress on Pain: Abstracts, Montreal, QC (2010) [E3]
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2010 |
Walsh MA, Farrell KE, Graham BA, Brichta AM, Callister RJ, 'Sodium current properties differ in neonate and adult superficial dorsal horn neurons', 13th World Congress on Pain: Abstracts, Montreal, QC (2010) [E3]
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2010 |
Harris BM, Graham BA, Bolton PS, Brichta AM, Callister RJ, 'Influence of acute neck muscle inflammation on the excitability of superficial dorsal horn neurons', 13th World Congress on Pain: Abstracts, Montreal, QC (2010) [E3]
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2010 |
Hughes DI, Sah P, Callister RJ, Graham BA, 'Neuroanatomical and electrophysiological features of parvalbumin-expressing neurons in the rodent spinal dorsal horn', 13th World Congress on Pain: Abstracts, Montreal, QC (2010) [E3]
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2010 |
Graham BA, Hughes DI, Lim R, Sah P, Brichta AM, Callister RJ, 'Characterization of calretinin expressing interneurons in the superficial dorsal horn of the mouse spinal cord', 13th World Congress on Pain: Abstracts, Montreal, QC (2010) [E3]
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2009 |
Graham BA, Schofield PR, Callister RJ, 'Glycine receptor mediated synaptic transmission in the superficial dorsal horn of Spasmodic mice', ANS 2009 Abstracts: Posters, Canberra, ACT (2009) [E3]
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2009 |
Tadros MA, Anderson WB, Graham BA, Callister RJ, 'Responses to current injection differ between mouse cervical, thoracic and lumbar superficial dorsal horn neurons', ANS 2009 Abstracts: Posters, Canberra, ACT (2009) [E3]
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2008 |
Jobling P, Graham BA, Brichta AM, Callister RJ, 'In vivo patch clamp recording of synaptic events evoked in superficial dorsal horn neurons after stimulation of the female reproductive tract in the mouse', Proceedings of the Australian Neuroscience Society, Hobart, TAS (2008) [E3]
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2008 |
Callister RJ, Brichta AM, Graham BA, 'Beyond the dorsal horn: The use of animal models to discover new sites for pain therapy', Australian and New Zealand Journal of Psychiatry, Newcastle, NSW (2008) [E3]
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|||||||
2006 |
Anderson WB, Graham BA, Jobling P, Lim R, Brichta AM, Callister RJ, 'Glycine receptor diversity in the dorsal horn of the mouse spinal cord', Society for Neuroscience, Atlanta, GA (2006) [E3]
|
|||||||
2006 |
Jobling P, Graham BA, Brichta AM, Callister RJ, 'In vivo patch-clamp recording of subthreshold synaptic events evoked in dorsal horn neurons after stimulation of the female reproductive tract in the mouse', Society for Neuroscience, Atlanta, Georgia (2006) [E3]
|
|||||||
2006 |
Walsh MA, Graham BA, Brichta AM, Callister RJ, 'Postnatal development of electrophysiological properties in mouse supeficial dorsal horn neurones', Proceedings of the Australian Neuroscience Society, Sydney (2006) [E3]
|
|||||||
2005 |
Graham BA, Brichta AM, Callister RJ, 'Effect of Temperature on the Discharge Properties of Mouse Superficial Dorsal Horn Neurons', Proceedings of the Australian Neuroscience Society, Perth (2005) [E3]
|
|||||||
2005 |
Callister RJ, Graham BA, Brichta AM, 'In Vivo Responses of Mouse Spinal Neurones to Electrical and Functionally-Relevant Stimulation', Proceedings of the Australian Neuroscience Society Conference, Perth (2005) [E3]
|
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Show 32 more conferences |
Preprint (7 outputs)
Year | Citation | Altmetrics | Link | |||||
---|---|---|---|---|---|---|---|---|
2023 |
Mitchell C, Campbell E, Fisher S, Stanton L, Burton N, Pearl A, et al., 'Optogenetic recruitment of hypothalamic corticotrophin-releasing-hormone (CRH) neurons reduces motivational drive (2023)
|
|||||||
2023 |
Iredale J, Pearl A, Callister R, Dayas C, Manning E, Graham B, ' Optical Von-Frey method to determine nociceptive thresholds: a novel paradigm for preclinical pain assessment and analgesic screening (2023)
|
|||||||
2020 |
Mitchell C, Fisher S, Yeoh J, Pearl A, Burton N, Bains J, et al., 'A ventral striatal-orexin/hypocretin circuit modulates approach but not consumption of food (2020)
|
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Show 4 more preprints |
Grants and Funding
Summary
Number of grants | 47 |
---|---|
Total funding | $8,441,342 |
Click on a grant title below to expand the full details for that specific grant.
20233 grants / $789,349
Network level decoding of touch and pain in the spinal cord$742,843
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Brett Graham, Doctor Marc Russo, Marc Russo, Doctor Jeremy Stoddard, Associate Professor James Welsh |
Scheme | Ideas Grants |
Role | Lead |
Funding Start | 2023 |
Funding Finish | 2025 |
GNo | G2200345 |
Type Of Funding | C1100 - Aust Competitive - NHMRC |
Category | 1100 |
UON | Y |
An Optogenetic Mouse model for pre-clinical pain therapeutics screening: A proof of concept study to treat Neuropathic pain$23,253
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Professor Brett Graham, Doctor Jacqueline Iredale |
Scheme | Industry Matched Funding Scheme |
Role | Lead |
Funding Start | 2023 |
Funding Finish | 2023 |
GNo | G2300407 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
An Optogenetic Mouse model for pre-clinical pain therapeutics screening: A proof of concept study to treat Neuropathic pain$23,253
Funding body: Novatrad Pharma Pty Ltd
Funding body | Novatrad Pharma Pty Ltd |
---|---|
Project Team | Professor Brett Graham |
Scheme | Research Project |
Role | Lead |
Funding Start | 2023 |
Funding Finish | 2023 |
GNo | G2300980 |
Type Of Funding | C3100 – Aust For Profit |
Category | 3100 |
UON | Y |
20222 grants / $514,503
Hunger flexibly modifies hypothalamic neural circuits responding to threat.$375,003
Funding body: ARC (Australian Research Council)
Funding body | ARC (Australian Research Council) |
---|---|
Project Team | Professor Chris Dayas, Prof Zane Andrews, Professor Brett Graham, Doctor Lizzie Manning |
Scheme | Discovery Projects |
Role | Investigator |
Funding Start | 2022 |
Funding Finish | 2025 |
GNo | G2200223 |
Type Of Funding | C1200 - Aust Competitive - ARC |
Category | 1200 |
UON | Y |
Optogenetic research to advance chronic pain treatments$139,500
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Brett Graham, Student Un-named |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2022 |
Funding Finish | 2025 |
GNo | G2200255 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
20203 grants / $705,892
Projection neuron axon collaterals in the dorsal horn: the missing link in spinal pain processing?$513,873
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Brett Graham, Conjoint Professor Robert Callister, Dr David Hughes |
Scheme | Ideas Grants |
Role | Lead |
Funding Start | 2020 |
Funding Finish | 2022 |
GNo | G1900492 |
Type Of Funding | C1100 - Aust Competitive - NHMRC |
Category | 1100 |
UON | Y |
HMRI Equipment Grant for a spinning disc confocal microscope$100,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Brett Graham |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2020 |
Funding Finish | 2020 |
GNo | G2001358 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
Microelectrode array screening of cannabinoid compounds in spinal pain circuits$92,019
Funding body: CannaPacific Pty Ltd
Funding body | CannaPacific Pty Ltd |
---|---|
Project Team | Professor Brett Graham |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2020 |
Funding Finish | 2022 |
GNo | G2000799 |
Type Of Funding | C3100 – Aust For Profit |
Category | 3100 |
UON | Y |
20191 grants / $773,659
A novel pathways linking stress with mood disorders$773,659
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Chris Dayas, Professor Brett Graham |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2019 |
Funding Finish | 2021 |
GNo | G1800444 |
Type Of Funding | C1100 - Aust Competitive - NHMRC |
Category | 1100 |
UON | Y |
20184 grants / $1,323,437
Excitatory interneurons: a sensory amplifier for pathological pain $668,810
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Brett Graham, Conjoint Professor Robert Callister, Professor Chris Dayas, Dr David Hughes |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2018 |
Funding Finish | 2020 |
GNo | G1700334 |
Type Of Funding | C1100 - Aust Competitive - NHMRC |
Category | 1100 |
UON | Y |
All-optical manipulation and recording of neural circuit activity$415,000
Funding body: ARC (Australian Research Council)
Funding body | ARC (Australian Research Council) |
---|---|
Project Team | Professor Gavan McNally; Professor Bernard Balleine; Associate Professor Christopher Dayas; Professor Rick Richardson; Professor Andrew Killcross; Professor Alan Brichta; Associate Professor Brett Graham |
Scheme | Linkage Infrastructure Equipment & Facilities (LIEF) |
Role | Investigator |
Funding Start | 2018 |
Funding Finish | 2018 |
GNo | |
Type Of Funding | C1200 - Aust Competitive - ARC |
Category | 1200 |
UON | N |
Supporting Optogenetic Research to advance chronic back pain treatments$139,627
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Brett Graham, Mr Tyler Browne |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2018 |
Funding Finish | 2021 |
GNo | G1801133 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
All-optical manipulation and recording of neural circuit activity$100,000
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Professor Chris Dayas, Professor Alan Brichta, Professor Gavan McNally, Professor Brett Graham, McNully, Gavan |
Scheme | Equipment Grant |
Role | Investigator |
Funding Start | 2018 |
Funding Finish | 2018 |
GNo | G1700451 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
20174 grants / $655,121
Hypothalamic Control Of Motivated Behavior$513,150
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Chris Dayas, Professor Brett Graham, Professor Gavan McNally, Dr Jaideep Bains |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2017 |
Funding Finish | 2019 |
GNo | G1600298 |
Type Of Funding | Aust Competitive - Commonwealth |
Category | 1CS |
UON | Y |
Using New Light-Based Approaches to Study Chronic Pain$67,471
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Brett Graham, Associate Professor Phil Jobling, Ms Kelly Smith |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2017 |
GNo | G1700526 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
CBMHR Research$54,500
Funding body: Hunter New England Local Health District
Funding body | Hunter New England Local Health District |
---|---|
Project Team | Professor Brett Graham, Professor Brian Kelly, Professor Alan Brichta, Professor Frini Karayanidis |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2017 |
GNo | G1700759 |
Type Of Funding | C2400 – Aust StateTerritoryLocal – Other |
Category | 2400 |
UON | Y |
Three-dimensional characterisation of a potential neuropathic pain$20,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Dr JAMIE Flynn, Professor Brett Graham |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2017 |
GNo | G1700090 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
20163 grants / $550,121
Mechanisms underlying efferent feedback in the vestibular system$510,121
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Alan Brichta, Professor Brett Graham, Associate Professor Rebecca Lim, Conjoint Professor Robert Callister, Professor Chris Dayas, Dr Chris Holt, Professor Richard Rabbitt |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2016 |
Funding Finish | 2019 |
GNo | G1500239 |
Type Of Funding | C1100 - Aust Competitive - NHMRC |
Category | 1100 |
UON | Y |
The Resilient Brain Initiative - Preclinical Neurobiology Group$30,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Chris Dayas, Professor Brett Graham |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2016 |
Funding Finish | 2016 |
GNo | G1601532 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
Jennie Thomas Medical Research Travel Grant$10,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Brett Graham, Miss Kelly Smith |
Scheme | Jennie Thomas Medical Research Travel Grant |
Role | Lead |
Funding Start | 2016 |
Funding Finish | 2017 |
GNo | G1600729 |
Type Of Funding | Grant - Aust Non Government |
Category | 3AFG |
UON | Y |
20151 grants / $22,000
Electrophysiology rig for the study of schizophrenia-related changes in white matter neurons after maternal infection$22,000
Funding body: Rebecca L Cooper Medical Research Foundation Ltd
Funding body | Rebecca L Cooper Medical Research Foundation Ltd |
---|---|
Project Team | Associate Professor Paul Tooney, Associate Professor Phil Jobling, Professor Brett Graham, Emeritus Professor Deborah Hodgson, Emeritus Professor Patricia Michie, Doctor Lauren Harms |
Scheme | Research Grant |
Role | Investigator |
Funding Start | 2015 |
Funding Finish | 2015 |
GNo | G1400999 |
Type Of Funding | Grant - Aust Non Government |
Category | 3AFG |
UON | Y |
20144 grants / $1,055,586
Spinal processing of sensory signals from the gut$554,477
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Conjoint Professor Robert Callister, Professor Simon Keely, Professor Brett Graham, Professor Alan Brichta, Dr David Hughes |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2014 |
Funding Finish | 2017 |
GNo | G1300361 |
Type Of Funding | Aust Competitive - Commonwealth |
Category | 1CS |
UON | Y |
Microglia as primary drivers of stress-induced changes in neuronal connectivity$475,782
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Rohan Walker, Professor Brett Graham |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2014 |
Funding Finish | 2017 |
GNo | G1300330 |
Type Of Funding | Aust Competitive - Commonwealth |
Category | 1CS |
UON | Y |
Neurophysiological investigation of neurons in the white matter – affects of maternal infection and relevance to Schizophrenia.$15,000
Funding body: Schizophrenia Research Institute
Funding body | Schizophrenia Research Institute |
---|---|
Project Team | Associate Professor Paul Tooney, Associate Professor Phil Jobling, Professor Brett Graham |
Scheme | Postgraduate Research Scholarship |
Role | Investigator |
Funding Start | 2014 |
Funding Finish | 2016 |
GNo | G1301321 |
Type Of Funding | C3200 – Aust Not-for Profit |
Category | 3200 |
UON | Y |
Neurobiological Investigation of Interstitial White Matter Neurons in a Maternal Infection Activation Model of Schizophrenia$10,327
Funding body: Australian Rotary Health
Funding body | Australian Rotary Health |
---|---|
Project Team | Associate Professor Paul Tooney, Associate Professor Phil Jobling, Professor Brett Graham |
Scheme | Ian Scott Scholarship |
Role | Investigator |
Funding Start | 2014 |
Funding Finish | 2018 |
GNo | G1301103 |
Type Of Funding | C3200 – Aust Not-for Profit |
Category | 3200 |
UON | Y |
20131 grants / $482,705
The role of presynaptic inhibition in neuropathic pain$482,705
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Brett Graham, Conjoint Professor Robert Callister, Professor George Augustine, Dr David Hughes |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2013 |
Funding Finish | 2015 |
GNo | G1200088 |
Type Of Funding | Aust Competitive - Commonwealth |
Category | 1CS |
UON | Y |
20122 grants / $22,000
Characterizing psychostimulant-induced synaptic plasticity in the hypothalamus$20,000
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Professor Chris Dayas, Professor Brett Graham |
Scheme | Near Miss Grant |
Role | Investigator |
Funding Start | 2012 |
Funding Finish | 2012 |
GNo | G1200677 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
14th World Congress on Pain (International Association for the Study of Pain), Milan Italy, 26-31 August 2012$2,000
Funding body: University of Newcastle - Faculty of Health and Medicine
Funding body | University of Newcastle - Faculty of Health and Medicine |
---|---|
Project Team | Professor Brett Graham |
Scheme | Travel Grant |
Role | Lead |
Funding Start | 2012 |
Funding Finish | 2012 |
GNo | G1200544 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
20111 grants / $20,000
How do the immune and nervous systems interact in arthritis?$20,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Associate Professor Phil Jobling, Professor Brett Graham |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2011 |
Funding Finish | 2011 |
GNo | G1000987 |
Type Of Funding | Contract - Aust Non Government |
Category | 3AFC |
UON | Y |
20107 grants / $1,088,803
Spinal mechanism underlying arthritic joint pain$416,500
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Brett Graham |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2010 |
Funding Finish | 2012 |
GNo | G0190192 |
Type Of Funding | Aust Competitive - Commonwealth |
Category | 1CS |
UON | Y |
Laser microdissection microscopy system for cell and development biology$350,000
Funding body: ARC (Australian Research Council)
Funding body | ARC (Australian Research Council) |
---|---|
Project Team | Professor Eileen McLaughlin, Conjoint Professor Keith Jones, Distinguished Emeritus Professor John Aitken, Professor Brett Nixon, Doctor Shaun Roman, Professor Alan Brichta, Doctor Rick Thorne, Associate Professor Doug Smith, Aprof DAVID McCurdy, Emeritus Professor Ray Rose, Professor Christopher Grof, Emeritus Professor Leonie Ashman, Professor Gordon Burns, Professor Brett Graham, Associate Professor Paul Tooney, Laureate Professor Roger Smith, Professor Paul Foster, Professor Trevor Day, Conjoint Professor Robert Callister |
Scheme | Linkage Infrastructure Equipment & Facilities (LIEF) |
Role | Investigator |
Funding Start | 2010 |
Funding Finish | 2010 |
GNo | G0190369 |
Type Of Funding | Scheme excluded from IGS |
Category | EXCL |
UON | Y |
Laser microdissection microscopy system for cell and development biology$215,000
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Professor Eileen McLaughlin, Conjoint Professor Keith Jones, Distinguished Emeritus Professor John Aitken, Professor Brett Nixon, Doctor Shaun Roman, Professor Alan Brichta, Doctor Rick Thorne, Associate Professor Doug Smith, Aprof DAVID McCurdy, Emeritus Professor Ray Rose, Professor Christopher Grof, Emeritus Professor Leonie Ashman, Professor Gordon Burns, Professor Brett Graham, Associate Professor Paul Tooney, Laureate Professor Roger Smith, Professor Paul Foster, Professor Trevor Day, Conjoint Professor Robert Callister |
Scheme | Equipment Grant |
Role | Investigator |
Funding Start | 2010 |
Funding Finish | 2010 |
GNo | G1000874 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
Laser microdissection microscopy system for cell and development biology (HMRI contribution towards 2010 ARC LIEF grant)$50,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Eileen McLaughlin, Conjoint Professor Keith Jones, Distinguished Emeritus Professor John Aitken, Professor Brett Nixon, Doctor Shaun Roman, Professor Alan Brichta, Doctor Rick Thorne, Associate Professor Doug Smith, Aprof DAVID McCurdy, Emeritus Professor Ray Rose, Professor Christopher Grof, Emeritus Professor Leonie Ashman, Professor Gordon Burns, Professor Brett Graham, Associate Professor Paul Tooney, Laureate Professor Roger Smith, Professor Paul Foster, Professor Trevor Day, Conjoint Professor Robert Callister |
Scheme | Equipment Grant |
Role | Investigator |
Funding Start | 2010 |
Funding Finish | 2010 |
GNo | G1000144 |
Type Of Funding | Other Public Sector - State |
Category | 2OPS |
UON | Y |
ABI 7500 Real Time PCR System $34,000
Funding body: NHMRC (National Health & Medical Research Council)
Characterising the synaptic physiology of orexin neurons in response to cocaine: Implications for drug relapse$21,303
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Chris Dayas, Professor Brett Graham |
Scheme | PULSE Early Career Researcher of the Year Award |
Role | Investigator |
Funding Start | 2010 |
Funding Finish | 2010 |
GNo | G0900151 |
Type Of Funding | Donation - Aust Non Government |
Category | 3AFD |
UON | Y |
13th World Congress on Pain, Montreal, Canada, 29 August - 2 September 2010$2,000
Funding body: University of Newcastle - Faculty of Health and Medicine
Funding body | University of Newcastle - Faculty of Health and Medicine |
---|---|
Project Team | Professor Brett Graham |
Scheme | Travel Grant |
Role | Lead |
Funding Start | 2010 |
Funding Finish | 2011 |
GNo | G1000533 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
20094 grants / $64,644
Neurometer CPT/C$28,435
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Philip Bolton, Conjoint Professor Robert Callister, Professor Alan Brichta, Emeritus Professor Robin Callister, Professor Brett Graham, Associate Professor Phil Jobling |
Scheme | Equipment Grant |
Role | Investigator |
Funding Start | 2009 |
Funding Finish | 2009 |
GNo | G0189845 |
Type Of Funding | Other Public Sector - Commonwealth |
Category | 2OPC |
UON | Y |
Leica VT1200S - Fully automated vibrating blade microtome$16,209
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Conjoint Professor Robert Callister, Professor Alan Brichta, Conjoint Professor Keith Jones, Professor Jon Hirst, Professor Brett Graham, Professor Philip Bolton, Associate Professor Phil Jobling, Associate Professor Paul Tooney, Doctor Angela McPherson, Associate Professor Rebecca Lim, Doctor Ramatis De Oliveira, Mr Matthew Walsh |
Scheme | Equipment Grant |
Role | Investigator |
Funding Start | 2009 |
Funding Finish | 2009 |
GNo | G0189842 |
Type Of Funding | Other Public Sector - Commonwealth |
Category | 2OPC |
UON | Y |
Spinal mechanisms of chronic pain in arthritis$15,000
Funding body: Arthritis Australia
Funding body | Arthritis Australia |
---|---|
Project Team | Professor Brett Graham |
Scheme | Grant-In-Aid |
Role | Lead |
Funding Start | 2009 |
Funding Finish | 2009 |
GNo | G0189342 |
Type Of Funding | Aust Competitive - Non Commonwealth |
Category | 1NS |
UON | Y |
New Staff Grant 2009$5,000
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Professor Brett Graham |
Scheme | New Staff Grant |
Role | Lead |
Funding Start | 2009 |
Funding Finish | 2009 |
GNo | G0189912 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
20082 grants / $299,000
Mechanisms underlying vestibular cortical representation$279,000
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Brett Graham |
Scheme | Early Career Fellowships |
Role | Lead |
Funding Start | 2008 |
Funding Finish | 2011 |
GNo | G0188073 |
Type Of Funding | Aust Competitive - Commonwealth |
Category | 1CS |
UON | Y |
Leica VT2100S Vibrating Microtome$20,000
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Alan Brichta, Conjoint Professor Robert Callister, Professor Dirk Van Helden, Professor Philip Bolton, Associate Professor Rebecca Lim, Professor Brett Graham, Dr Marcus Howlett, Doctor Angela McPherson, Doctor Mohammad Imtiaz, Doctor Ramatis De Oliveira, Mr Wayne Anderson, Mr Matthew Walsh |
Scheme | Equipment Grant |
Role | Investigator |
Funding Start | 2008 |
Funding Finish | 2008 |
GNo | G0188540 |
Type Of Funding | Other Public Sector - Commonwealth |
Category | 2OPC |
UON | Y |
20074 grants / $66,182
High speed/sensitivity CCD camera$30,000
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Dirk Van Helden, Professor Eileen McLaughlin, Professor Gordon Burns, Doctor Rick Thorne, Dr Marcus Howlett, Doctor Mohammad Imtiaz, Professor Alan Brichta, Conjoint Professor Robert Callister, Professor Brett Graham, Professor Derek Laver, Prof LIZ Milward, Associate Professor John Holdsworth |
Scheme | Equipment Grant |
Role | Investigator |
Funding Start | 2007 |
Funding Finish | 2007 |
GNo | G0188196 |
Type Of Funding | Other Public Sector - Commonwealth |
Category | 2OPC |
UON | Y |
Identifying new spinal cord targets for pain management.$14,252
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Brett Graham, Conjoint Professor Robert Callister |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2007 |
Funding Finish | 2007 |
GNo | G0187234 |
Type Of Funding | Contract - Aust Non Government |
Category | 3AFC |
UON | Y |
Identifying new spinal cord targets for pain management$14,252
Funding body: Hunter Medical Research Institute (HMRI)
Funding body | Hunter Medical Research Institute (HMRI) |
---|---|
Project Team | Brett Anthony Graham |
Scheme | HMRI Brain and Mental Health Research Program |
Role | Lead |
Funding Start | 2007 |
Funding Finish | 2007 |
GNo | |
Type Of Funding | Aust Competitive - Commonwealth |
Category | 1CS |
UON | N |
Developing a rodent model to study neck pain$7,678
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Conjoint Professor Robert Callister, Professor Philip Bolton, Professor Alan Brichta, Professor Brett Graham |
Scheme | Pilot Grant |
Role | Investigator |
Funding Start | 2007 |
Funding Finish | 2007 |
GNo | G0187879 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
20051 grants / $8,340
Attend the Society for Neurosciences 35th Annual Meeting in Washington DC USA 12 to 16 November 2005 & visit labs of Prof Maria Fitzgerald & Dr Troy Margrie University College London UK$8,340
Funding body: NSW Ministry for Science and Medical Research
Funding body | NSW Ministry for Science and Medical Research |
---|---|
Project Team | Professor Brett Graham |
Scheme | Spinal Cord Injury & Other Neurological Conditions Travel Scholarships |
Role | Lead |
Funding Start | 2005 |
Funding Finish | 2005 |
GNo | G0185447 |
Type Of Funding | Not Known |
Category | UNKN |
UON | Y |
Research Supervision
Number of supervisions
Current Supervision
Commenced | Level of Study | Research Title | Program | Supervisor Type |
---|---|---|---|---|
2022 | PhD | Developing Therapeutic Options for Chronic Pelvic Pain | PhD (Human Physiology), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2021 | PhD | Understanding the Early Stages of Alzheimer’s Disease | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
Past Supervision
Year | Level of Study | Research Title | Program | Supervisor Type |
---|---|---|---|---|
2024 | PhD | Investigating the Role of Striatal Direct and Indirect Pathway Spiny Projection Neurons in a Cocaine-Induced Impairment of Goal-Directed Behavioural Control | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2024 | PhD | Shining Light on the Contribution of Spinal Projection Neurons to the Local Spinal Cord and Wider Nervous System | PhD (Human Physiology), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2023 | PhD | Using Chemical and Light Activation of Neurons to Study Pain Mechanisms and Screen Analgesic Compounds | PhD (Human Physiology), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2023 | PhD | Classical Approaches versus Modern Molecular Techniques to Dissect Neuronal Heterogeneity in the Dorsal Horn: Opposite Ends of the Same Spectrum? | PhD (Human Physiology), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2022 | PhD | How do Medial Amygdala (MeA) Excitatory Neurons Control Behavioural Responses to Olfactory Stimuli? | PhD (Medical Genetics), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2022 | PhD | Understanding the Impact of Addictive Drugs on Stress Circuits | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2020 | PhD | Model Perturbations of Glial Synaptomodulatory and Immune Functions | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2019 | PhD | The Role of Parvalbumin+ Interneurons in Spinal Sensory Coding | PhD (Human Physiology), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2018 | PhD | The Role of Calretinin Positive Interneurons in Spinal Sensory Coding | PhD (Human Physiology), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2018 | PhD | Channelrhodopsin-Assisted Circuit Mapping of Medial Amygdaloid Connectivity to the Paraventricular Nucleus of the Hypothalamus | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2017 | PhD | Investigation of Visceral Sensory Processing Mechanisms in the Superficial Dorsal Horn of the Spinal Cord | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2015 | PhD | Electrophysiological Investigation of Spinal Cord Injury and Characterisation of Propriospinal Neurons | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2015 | PhD | Drug-induced Changes to the Lateral Hypothalamic Circuits and Downstream Projection Targets | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2012 | Masters | The Effect of Neck Muscle Inflammation on Neuronal Excitability in the Dorsal Horn of the Spinal Cord | M Philosophy (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
Research Collaborations
The map is a representation of a researchers co-authorship with collaborators across the globe. The map displays the number of publications against a country, where there is at least one co-author based in that country. Data is sourced from the University of Newcastle research publication management system (NURO) and may not fully represent the authors complete body of work.
Country | Count of Publications | |
---|---|---|
Australia | 78 | |
United Kingdom | 25 | |
United States | 14 | |
Japan | 7 | |
Canada | 4 | |
More... |
News
News • 15 Dec 2022
Spinal cord pain to PTSD: $5.2m in NHMRC grants to target pressing medical conditions
Both the body and the mind will be a key focus for innovative researchers from the University of Newcastle, who were successful in the latest round of National Health and Medical Research Council (NHMRC) Ideas Grants.
News • 18 Dec 2019
NHMRC awards $9.3 million to 13 University of Newcastle projects
The University of Newcastle has received more than $9.3 million in funding to support projects aiming to solve some of the world’s most critical health problems and improve the lives of millions of Australians.
News • 30 Apr 2015
Microscope to shed light on mental health
A laser-equipped microscope that gives brain researchers unparalleled insight into mental illness has just been installed at the University of Newcastle.
Professor Brett Graham
Position
Professor
School of Biomedical Sciences and Pharmacy
College of Health, Medicine and Wellbeing
Focus area
Anatomy
Contact Details
brett.graham@newcastle.edu.au | |
Phone | (02) 4921 5397 |
Fax | (02) 4921 7906 |
Link | UoN Blogs |
Office
Room | MS411 |
---|---|
Building | Medical Sciences |
Location | Callaghan University Drive Callaghan, NSW 2308 Australia |