Dr Lizzie Manning
Senior Lecturer Physiology
School of Biomedical Sciences and Pharmacy
- Email:lizzie.manning@newcastle.edu.au
- Phone:+61 2 4055 0154
Studying brain changes to better treat mental health
Neuroscience researcher and senior lecturer Dr Lizzie Manning is big on the brain, particularly its role in mental health. By carrying out research to understand neural activity, she hopes to create a future with more effective treatments.
Lizzie has always had an interest in how the brain works and mental health, in part sparked by having a sister with autism. She also saw friends and other family members go through mental illness and how difficult it is.
It was this interest that sent her on a journey into neuroscience research back in 2009.
After completing an undergraduate degree in Biomedical Sciences and a PhD in neuroscience at The University of Melbourne and the Florey Institute of Neuroscience and Mental Health (The Florey)—the largest brain research centre in the Southern Hemisphere—she headed to the Department of Psychiatry at the University of Pittsburgh in the US to do her postdoc.
The department was very mental health-focused, and it was here that she began working in the translational obsessive-compulsive disorder (OCD) laboratory run by psychiatrist A/Prof Susanne Ahmari.
“I learned a lot from Susanne and how to bridge the translational gap between preclinical and clinical work”, says Lizzie. “I also gained new skills in in vivo calcium imaging and optogenetics, preclinical OCD models and operant cognitive paradigms.”
Developing an understanding of OCD
One of the unique angles they focused on in the US was how different aspects of inflexible behaviour arise in OCD.
“The obsessions in OCD can be understood as inflexible thoughts. These are anxiety-provoking thoughts that are really intrusive; people can’t just ignore them. Similarly, the compulsions are inflexible actions: patients can’t stop themselves from doing them. When you give people with OCD a psychological task, this can also be used to measure inflexibility in different aspects of decision-making,” says Lizzie.
To understand whether these different aspects of inflexibility in OCD share a common basis in the brain, they looked at animal models in her preclinical research to see if the brains of OCD models look different in terms of dysfunctional cells. As a result, they found mostly different patterns associated with repetitive, compulsive behaviours and decision-making.
After returning to Australia in 2020, Lizzie began working at the University of Newcastle. Two years later, when she was appointed to a continuing lecturer position, she started building on this research in her new lab.
To aid this work, she secured a sizeable Ideas Grant of $644,000 from the National Health and Medical Research Council (NHMRC).
But while in the US, she was focused on cells in the cortex (the grey matter or outer layer), she’s now headed south into the subcortical region, an area that’s really important for flexible control of behaviour.
Lizzie shares: “There are two subcortical pathways: one that tends to promote movements or actions, and another opposing pathway that tends to inhibit action. We’re trying to understand how balance between these two pathways is involved with different aspects of inflexible behaviour in OCD.”
The goal now is to dig a bit deeper into this.
Inflexibility across the mental health spectrum
The whole idea around inflexible behaviours is something Lizzie says is fairly broadly applicable across mental health, and her focus isn’t solely on OCD.
“For example, I’ve worked on other projects around inflexible behaviour, such as Tourette’s syndrome, a condition of the nervous system that’s closely related to OCD. People with Tourette’s have tics, which are difficult to control behaviours, so the way to understand it is similar.”
In another vein (or cerebral pathway!), she also points out the rigid, inflexible patterns of behaviour and decision-making seen in people with clinical depression. It’s not just an energy and motivation thing, she says.
“It can actually be a fundamental neural and decision-making change that happens.”
Stress and the hypothalamus
Her work around depression is linked to other research Lizzie is carrying out alongside Professor Chris Dayas, Assistant Dean Research and Innovation in the College of Health, Medicine and Wellbeing.
Chris’ interest is in the body’s central nervous system, which involves a lot of work on stress and the hypothalamus—a part of the brain that controls our stress hormone system, as well as hunger, body temperature, heart rate and mood.
“Together, we’re looking at what aspects of the brain control our responses to stress— how they become maladaptive—which contributes to stress-related mental illness, and how we can make them more adaptive. In other words, which brain changes underlie it”, she says.
In the group, they’re also looking at substance use disorders, such as illicit drugs and alcohol (see DECRA fellow Erin Campbell), and other inflexible behaviours involved in these disorders.
Digging deeper with other disciplines
These types of scientific collaborations are of huge value when it comes to digging into the brain. However, working with others doesn’t stop in the research lab.
Lizzie shares that understanding the organ in our heads isn’t just the job of neuroscientists. It also involves working with people with advanced skills in complex mathematics, engineering and other disciplines.
One such collaboration Lizzie and her team are involved in in Newcastle is with psychiatrist and computational neuroscientist Professor Michael Breakspear, who works at Hunter Imaging Centre. They also have a co-supervised PhD student.
“The benefit here is that they can help understand the brain and its complexity. It’s a mathematical understanding, modelling how the brain works and how neural activity changes give rise to behaviour changes.”
By working together, we hope to solve these big problems that haven’t yet been solved.”
A view to better treatments—and lives
The end goal for Lizzie and her teams of collaborators is to help people suffering from mental health-disorders that have traditionally been treated more superficially at a behaviour level rather than being treated as a disease of the brain.
“The hope is that we’ll be able to develop more targeted treatments that actually impact symptoms through specific neural activity changes. Currently, we tend to use things like antidepressants, which are fairly non-specific. While they do have some indirect effect on helping symptoms, they don’t cure people and are often associated with off-target side effects.”
By understanding the brain activity patterns that directly underlie these behaviours, they hope to develop drug treatments or brain stimulation therapy to normalise it.
In fact, some of the new research in Lizzie’s lab is interested in understanding how non-invasive brain stimulation, with a method called ‘transcranial magnetic stimulation’ (TMS), can impact the cells and pathways in the brain involved in inflexible behaviour.
Reducing stigma; increasing diversity
While the main part of Lizzie’s work is focused on the neuroscience side, she’s keen to share that she’s also committed to working on the stigma and misunderstandings surrounding mental health—something that can be a huge barrier to getting good treatments.
“We might develop the best treatment, but if there’s still some stigma and misunderstanding, it’s not going to get to the people that need it.”
In pursuit of this, she continues to ensure that new advances in understanding mental illness and the brain are shared more broadly with the community. For example, in the US, she helped establish an annual art exhibition featuring works from people with mental illness alongside works from scientists studying the brain. This helps get conversations happening.
In addition to the stigma, another challenge Lizzie mentions is the overall goal of improving academic equity. People from different backgrounds, including First Nations people, can bring fresh perspectives and experiences to research.
This is improving, and the University of Newcastle is a leader in equity and diversity in academia in Australia. But Lizzie hopes that by contributing to programs that allow a broader spectrum of people to do research looking at the brain, even greater progress can be made.
Studying brain changes to better treat mental health
Dr Lizzie Manning is carrying out research to better understand neural activity, with the goal of developing more effective mental health treatments.
Career Summary
Biography
My research aims to improve outcomes for people affected by psychiatric disorders that feature inflexible behaviour patterns, such as obsessive compulsive disorder (OCD), depression and Tourette’s syndrome. I achieve this by investigating the neural mechanisms that contribute to inflexible behaviours, using my unique and cutting-edge neuroscience techniques with gold standard preclinical models of disease. Only with this understanding can we develop appropriate therapeutics that target the affected neural mechanisms directly. This will be a significant advance over the “sledgehammer” approach used currently, where therapeutics affect neurochemistry throughout the brain and body, resulting in moderate symptom improvements alongside a high incidence of adverse side-effects. My research responds to the urgent need for new neuroscience-guided novel therapeutics that directly treat the cause of disease pathophysiology, to improve health and quality of life for those affected. If you want to know more about OCD and current treatments available in Australia, check out a Conversation article I wrote with clinical collaborators.
I moved to the University of Newcastle in 2020 to start a Level B research associate position in the school of Biomedical Sciences ad Pharmacy with Prof Chris Dayas, and later transitioned to an independent lecturer position (2022) followed by promotion to Senior Lecturer (2024). Prior to this, following the completion of my PhD in 2014 at the Florey Neuroscience Institute and University of Melbourne with Prof Maarten van den Buuse, I moved to the USA to complete postdoctoral training at the University of Pittsburgh (USA) in the translational OCD laboratory directed by A/Prof Susanne Ahmari. Working under the supervision of a psychiatrist running a translational neuroscience laboratory really shaped my perspective as a preclinical researcher. During this time I trained in the use of Inscopix miniature microscopes and optogenetics to precisely characterize neural activity patterns that underly pathological behaviours. I applied these methods to study cortico-striatal contributions to behavioural disturbances relevant to OCD in the Sapap3 knockout mouse (You can follow these links to read my papers on cortical and striatal dysfunction in this model).
During my time at the University of Newcastle, I have commenced new projects extending my postdoctoral research in the USA, and I have also developed new projects on the role of the hypothalamus and basal ganglia circuitry in the development of inflexible behaviour and motivational disturbances relevant to psychiatric disorders. My growing independent research in the neuroscience theme at the University of Newcastle and the HMRI brain neuromodulation program is supported by early career grants from the Rebecca L Cooper foundation and Tourette Association of America, and more recently NHMRC and ARC funding. If you'd like to learn more about my research, please check out this webinar.
I also actively contribute to making academia more inclusive and attaining equity for marginalized scientists. I co-founded my school's Indigenous student engagement committee, am an ALLY network member, and also contribute to equity and diversity committees of national (ANS) and international (IBNS) neuroscience societies. I'm also passionate about community engagement and mental health awareness, and while working in the USA I co-founded and organised (2017-2018) an art event "Mindscapes" showcasing artwork from people with lived experience of mental illness and scientists from their research of the scientific basis of mental health. The goal of this event was to reduce stigma around mental illness by improving understanding through art. We also raised money through scientific art sales to donate to local mental health organizations supporting underserved communities.
Qualifications
- Doctor of Philosophy, University of Melbourne
Keywords
- calcium imaging
- neuroscience
- obsessive compulsive disorder
- psychiatry
- schizophrenia
- tourette syndrome
Languages
- English (Mother)
Fields of Research
Code | Description | Percentage |
---|---|---|
320903 | Central nervous system | 50 |
520202 | Behavioural neuroscience | 50 |
Professional Experience
UON Appointment
Title | Organisation / Department |
---|---|
Senior Lecturer Physiology | University of Newcastle College of Health, Medicine and Wellbeing Australia |
Academic appointment
Dates | Title | Organisation / Department |
---|---|---|
1/6/2020 - 31/1/2022 | Research Associate | School of Biomedical Sciences and Pharmcy, The University of Newcastle Australia |
1/8/2014 - 31/5/2020 |
Postdoctoral Associate Working in the lab of Susanne Ahmari (MD, PhD), I studied changes in cortico-striatal circuit function that contribute to the development of behavioural disturbances observed in OCD |
University of Pittsburgh Psychiatry United States |
1/7/2010 - 6/6/2014 |
PhD candidate Working in the lab of Maarten van den Buuse (PhD), I studied gene x environment interactions in the context of development of behavioural disturbances relevant to schizophrenia following adolescent exposure to methamphetamine |
The Florey Institute of Neuroscience and Mental Health Australia |
Awards
Award
Year | Award |
---|---|
2023 |
Early Faculty Travel Award (IBNS) International Behavioral Neuroscience Society |
2023 |
Mid-Career Research Award (CHMW) College Health, Medicine and Wellbeing - The University of Newcastle (Australia) |
2021 |
Early Career Achievement Award (IBNS) International Behavioral Neuroscience Society |
2019 |
Trainee Professional Development Award (SfN) Society for Neuroscience |
2014 |
Travel Award (IBNS) International Behavioral Neuroscience Society |
2014 |
Travel Award, Schizophrenia International Research Society (SIRS) biennial meeting Schizophrenia International Research Society |
2013 |
Jared Franklin Purton Travel award The Florey Institute of Neuroscience and Mental Health |
2013 |
Travel Award Neuro 2013 neuro2013 |
2012 |
The Miller Travel Fellowship The Florey Institute of Neuroscience and Mental Health |
Prize
Year | Award |
---|---|
2012 |
Graduate student of the Year Graduate Student Association, The University of Melbourne |
2008 |
Lavarack Prize for Developmental Biology The University of Melbourne |
Research Award
Year | Award |
---|---|
2018 |
Best Postdoctoral Poster Award Department of Psychiatry University of Pittsburgh annual research day |
2016 |
Data & Dine Symposium Poster Competition and Travel Award University of Pittsburgh Postdoctoral Association |
2015 |
Best Postdoctoral Poster Award Center for Neuroscience at the University of Pittsburgh (CNUP) Retreat |
2014 |
Best Poster Award, Schizophrenia International Research Society (SIRS) biennial meeting Schizophrenia International Research Society |
Scholarship
Year | Award |
---|---|
2010 |
Australian Postgraduate Award University of Melbourne |
2009 |
Frances Elizabeth Thomson Scholarship The University of Melbourne |
2007 |
Undergraduate research opportunities program (UROP) scholar Biomedical Research Victoria |
Invitations
Committee Member
Year | Title / Rationale |
---|---|
2019 | Co-chair, Membership and Communications committee, International Behavioral Neuroscience Society |
2016 | Society for Biological Psychiatry Travel award committee |
2013 | Biological Psychiatry Australia executive and annual meeting committees |
Grant Reviews
Year | Grant | Amount |
---|---|---|
2024 |
Investigator GRP C1100 - Aust Competitive - NHMRC - 1100, C1100 - Aust Competitive - NHMRC - 1100 |
$0 |
2023 |
Ideas GRP C1100 - Aust Competitive - NHMRC - 1100, C1100 - Aust Competitive - NHMRC - 1100 |
$0 |
Teaching
Code | Course | Role | Duration |
---|---|---|---|
HUBS2203 |
Introductory Pharmacology School of Biomedical Sciences and Pharmcy, The University of Newcastle This course provides students with knowledge of the basic mechanisms underlying the action of drugs on the body systems and with specialist knowledge of applied pharmacology and the rational use of medicines. |
Course Coordinator | 1/7/2022 - 30/6/2024 |
HUBS3403 |
Neuroscience School of Biomedical Sciences and Pharmcy, The University of Newcastle The purpose of this course is to provide the student with a broad understanding of neuroscience. In covering cellular, behavioural, and pathological aspects of neuroscience, the student is introduced to some of the most challenging issues in the field today, along with the most advanced research tools used to probe these issues. Students will gain knowledge of neuroanatomy, molecular and physiological features of the nervous system through exposure to one or more of lectures, tutorials/workshops/discussions and laboratory classes. The course is divided into 4 major blocks: 1. Basic Organisation and Function of the Nervous System 2. The Sensorimotor Systems 3. Neurobiology of Aging and Neurodegeneration 4. Neurobiology of Mental Health Disorders Particular emphasis will be placed on neuronal function, plasticity and degeneration, on important neurotransmitter systems, on the organisation of the central nervous system and methods to study the nervous system. Students will be introduced to some of the most relevant, unanswered questions and the latest research evidence in neuroscience. Students will be expected to apply the basic knowledge developed above to understand processes involved in major diseases and disorders of the central and peripheral nervous systems and to begin to think and critically analyse recent research in neuroscience. |
Lecturer | 26/2/2024 - 26/6/2024 |
PHAR3103 |
MENTAL AND NEUROLOGICAL HEALTH School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle Provide an introduction to basic neuroscience principles at the begining of the course on the pharmacological treatment of Mental and Neurological Disorders. |
Lecturer | 24/2/2021 - 26/2/2021 |
HUBS3204 |
BIOMEDICAL RESEARCH INTEGRATED LEARNING School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle Provide an overview about the Neuroscience research field and theme at the Univerity, as well as the "big questions" in neurosciences and some challenges for reproducibility and research quality in our field. |
Lecturer | 22/3/2021 - 16/4/2021 |
NROSCI 1042 |
Neurochemical Basis of Behavior University of Pittsburgh Guest lecturer (4 times) in an advanced neuroscience course for University of Pittsbrugh undergraduate students, presenting on the use of animals models in obsessive compulsive disorder research and cortico striatal circuit function |
Guest Lecturer | 1/4/2017 - 12/11/2019 |
PHAR6704 |
PHARMACOLOGY CHRONIC CONDITION School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle Designed new module on pharmacological treatment of psychiatric disorders |
Lecturer | 18/5/2021 - 22/5/2021 |
Publications
For publications that are currently unpublished or in-press, details are shown in italics.
Chapter (1 outputs)
Year | Citation | Altmetrics | Link | |||||
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2022 |
Hogarth S, Manning E, Buuse MVD, 'Chronic Methamphetamine and Psychosis Pathways', Handbook of Substance Misuse and Addictions: From Biology to Public Health 2121-2146 (2022) Methamphetamine is a highly addictive psychostimulant with increasing global abuse prevalence. The symptomatology of methamphetamine use includes a stimulant-induced psychosis, de... [more] Methamphetamine is a highly addictive psychostimulant with increasing global abuse prevalence. The symptomatology of methamphetamine use includes a stimulant-induced psychosis, defined by hallucinations and delusions, likened to those experienced in paranoid schizophrenia. Dopaminergic signaling in the mesocorticolimbic and nigrostriatal networks has been implicated in both the effects of chronic methamphetamine (METH) and in schizophrenia. This chapter will discuss research on the neural substrates involved in methamphetamine-induced psychosis. Inferences will also be drawn on future avenues of research and implications of our understanding of stimulant-induced psychosis for neural mechanisms within the brain governing other types of psychosis.
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Journal article (21 outputs)
Year | Citation | Altmetrics | Link | |||||
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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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Nova | ||||||
2024 |
Duchatel RJ, Jackson ER, Parackal SG, Kiltschewskij D, Findlay IJ, Mannan A, et al., 'PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma.', J Clin Invest, (2024) [C1]
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2023 |
Stanton LM, Price AJ, Manning EE, 'Hypothalamic corticotrophin releasing hormone neurons in stress-induced psychopathology: Revaluation of synaptic contributions', JOURNAL OF NEUROENDOCRINOLOGY, 35 (2023) [C1]
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Nova | ||||||
2023 |
Manning EE, Geramita MA, Piantadosi SC, Pierson JL, Ahmari SE, 'Distinct Patterns of Abnormal Lateral Orbitofrontal Cortex Activity During Compulsive Grooming and Reversal Learning Normalize After Fluoxetine', Biological Psychiatry, 93 989-999 (2023) [C1] Background: Patients with obsessive-compulsive disorder (OCD) display disrupted performance and abnormal lateral orbitofrontal cortex (LOFC) activity during reversal learning task... [more] Background: Patients with obsessive-compulsive disorder (OCD) display disrupted performance and abnormal lateral orbitofrontal cortex (LOFC) activity during reversal learning tasks. However, it is unknown whether compulsions and reversal learning deficits share a common neural substrate. To answer this question, we measured neural activity with in vivo calcium imaging in LOFC during compulsive grooming and reversal learning before and after fluoxetine treatment. Methods: Sapap3 knockout (KO) mice were used as a model for OCD-relevant behaviors. Sapap3 KOs and control littermates were injected with a virus encoding GCaMP6f and implanted with gradient-index lenses to visualize LOFC activity using miniature microscopes. Grooming, reversal learning, and neural activity were measured pre- and post-fluoxetine treatment (18 mg/kg, 4 weeks). Results: Baseline compulsive grooming and reversal learning impairments in KOs improved after fluoxetine treatment. In addition, KOs displayed distinct patterns of abnormal LOFC activity during grooming and reversal learning, both of which normalized after fluoxetine. Finally, reversal learning¿associated neurons were distributed randomly among grooming-associated neurons (i.e., overlap is what would be expected by chance). Conclusions: In OCD, LOFC is disrupted during both compulsive behaviors and reversal learning, but whether these behaviors share common neural underpinnings is unknown. We found that LOFC plays distinct roles in compulsive grooming and impaired reversal learning and their improvement with fluoxetine. These findings suggest that LOFC plays separate roles in pathophysiology and treatment of different perseverative behaviors in OCD.
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Nova | ||||||
2022 |
Hudson MR, Foreman J, Rind G, Manning EE, Jones NC, van den Buuse M, 'Differential Effects of Chronic Methamphetamine Treatment on High-Frequency Oscillations and Responses to Acute Methamphetamine and NMDA Receptor Blockade in Conscious Mice.', Brain sciences, 12 1503 (2022) [C1]
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Nova | ||||||
2021 |
Sepulveda M, Manning EE, Gogos A, Hale M, van den Buuse M, 'Long-term effects of young-adult methamphetamine on dorsal raphe serotonin systems in mice: Role of brain-derived neurotrophic factor', BRAIN RESEARCH, 1762 (2021) [C1]
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2021 |
Manning EE, Bradfield LA, Iordanova MD, 'Adaptive behaviour under conflict: Deconstructing extinction, reversal, and active avoidance learning', NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, 120 526-536 (2021) [C1]
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Nova | ||||||
2021 |
Manning EE, Wang AY, Saikali LM, Winner AS, Ahmari SE, 'Disruption of prepulse inhibition is associated with compulsive behavior severity and nucleus accumbens dopamine receptor changes in Sapap3 knockout mice', Scientific Reports, 11 (2021) [C1] Obsessive compulsive disorder (OCD) is associated with disruption of sensorimotor gating, which may contribute to difficulties inhibiting intrusive thoughts and compulsive rituals... [more] Obsessive compulsive disorder (OCD) is associated with disruption of sensorimotor gating, which may contribute to difficulties inhibiting intrusive thoughts and compulsive rituals. Neural mechanisms underlying these disturbances are unclear; however, striatal dopamine is implicated in regulation of sensorimotor gating and OCD pathophysiology. The goal of this study was to examine the relationships between sensorimotor gating, compulsive behavior, and striatal dopamine receptor levels in Sapap3 knockout mice (KOs), a widely used preclinical model system for OCD research. We found a trend for disruption of sensorimotor gating in Sapap3-KOs using the translational measure prepulse inhibition (PPI); however, there was significant heterogeneity in both PPI and compulsive grooming in KOs. Disruption of PPI was significantly correlated with a more severe compulsive phenotype. In addition, PPI disruption and compulsive grooming severity were associated with reduced dopamine D1 and D2/3 receptor density in the nucleus accumbens core (NAcC). Compulsive grooming progressively worsened in Sapap3-KOs tested longitudinally, but PPI disruption was first detected in high-grooming KOs at 7¿months of age. Through detailed characterization of individual differences in OCD-relevant behavioral and neurochemical measures, our findings suggest that NAcC dopamine receptor changes may be involved in disruption of sensorimotor gating and compulsive behavior relevant to OCD.
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2019 |
Corbit VL, Manning EE, Gittis AH, Ahmari SE, 'Strengthened Inputs from Secondary Motor Cortex to Striatum in a Mouse Model of Compulsive Behavior', JOURNAL OF NEUROSCIENCE, 39 2965-2975 (2019) [C1]
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2019 |
Manning EE, Dombrovski AY, Torregrossa MM, Ahmari SE, 'Impaired instrumental reversal learning is associated with increased medial prefrontal cortex activity in Sapap3 knockout mouse model of compulsive behavior', NEUROPSYCHOPHARMACOLOGY, 44 1494-1504 (2019) [C1]
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2018 |
Manning EE, Ahmari SE, 'How can preclinical mouse models be used to gain insight into prefrontal cortex dysfunction in obsessive-compulsive disorder?', Brain Neurosci Adv, 2 2398212818783896 (2018)
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2018 |
Jones NC, Hudson M, Foreman J, Rind G, Hill R, Manning EE, van den Buuse M, 'Brain-derived neurotrophic factor haploinsufficiency impairs high-frequency cortical oscillations in mice', European Journal of Neuroscience, 48 2816-2825 (2018) Schizophrenia is a complex psychiatric disorder with a heterogeneous aetiology involving genetic and environmental factors. Deficiencies in both brain-derived neurotrophic factor ... [more] Schizophrenia is a complex psychiatric disorder with a heterogeneous aetiology involving genetic and environmental factors. Deficiencies in both brain-derived neurotrophic factor (BDNF) and NMDA receptor function have been implicated in the disorder and may play causal and synergistic roles. Perturbations in the regulation of electrophysiological signals, including high-frequency (¿: 30¿80¿Hz and ß: 20¿30¿Hz) neuronal oscillations, are also associated with the disorder. This study investigated the influence of BDNF deficiency and NMDA receptor hypofunction on electrophysiological responses to brief acoustic stimuli. Adult BDNF heterozygote (BDNF+/-) and wild-type littermate C57Bl/6J mice were surgically implanted with EEG recording electrodes. All mice underwent EEG recording sessions to measure ongoing and auditory-evoked electrophysiological responses following treatment with MK-801 (0.3¿mg/kg ip) or vehicle. Western blotting on post-mortem cortical tissue assessed parvalbumin and GAD67 expression ¿ markers of interneurons which are involved in the generation of gamma oscillations. Compared with wild-type controls, BDNF+/- mice exhibited markedly dampened electrophysiological responses to auditory stimuli, including reductions in the amplitude of multiple components of the event-related potential and auditory-evoked oscillations, as well as reduced ongoing cortical gamma oscillations. MK-801 elevated ongoing gamma power but suppressed evoked gamma power, and this was observed equally across genotypes. BDNF+/- mice also displayed reductions in parvalbumin, but not GAD67 expression. We conclude that reduced BDNF expression leads to impairments in the generation of high-frequency neural oscillations, but this is not synergistic with NMDA receptor hypofunction. Reduced parvalbumin expression associated with BDNF haploinsufficiency may provide a molecular explanation for these electrophysiological deficits.
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2016 |
Manning EE, van den Buuse M, 'Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure', Behavioural Brain Research, 305 181-185 (2016) Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal mode... [more] Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia.
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2016 |
Manning EE, Halberstadt AL, Van Den Buuse M, 'BDNF-Deficient Mice Show Reduced Psychosis-Related Behaviors Following Chronic Methamphetamine', International Journal of Neuropsychopharmacology, 19 (2016) [C1] Background: One of the most devastating consequences of methamphetamine abuse is increased risk of psychosis. Brain-derived neurotrophic factor has been implicated in both psychos... [more] Background: One of the most devastating consequences of methamphetamine abuse is increased risk of psychosis. Brain-derived neurotrophic factor has been implicated in both psychosis and neuronal responses to methamphetamine. We therefore examined persistent psychosis-like behavioral effects of methamphetamine in brain-derived neurotrophic factor heterozygous mice. Methods: Mice were chronically treated with methamphetamine from 6 to 9 weeks of age, and locomotor hyperactivity to an acute D-amphetamine challenge was tested in photocell cages after a 2-week withdrawal period. Results: Methamphetamine-treated wild-type mice, but not brain-derived neurotrophic factor heterozygous mice, showed locomotor sensitization to acute 3mg/kg D-amphetamine. Qualitative analysis of exploration revealed tolerance to D-amphetamine effects on entropy in methamphetamine-treated brain-derived neurotrophic factor heterozygous mice, but not wild-type mice. Conclusions: Chronic methamphetamine exposure induces contrasting profiles of behavioral changes in wild-type and brain-derived neurotrophic factor heterozygous mice, with attenuation of behaviors relevant to psychosis in methamphetamine-treated brain-derived neurotrophic factor heterozygous mice. This suggests that brain-derived neurotrophic factor signalling changes may contribute to development of psychosis in methamphetamine users.
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Nova | ||||||
2014 |
Abayomi O, Amato D, Bailey C, Bitanihirwe B, Bowen L, Burshtein S, et al., 'The 4th Schizophrenia International Research Society Conference, 5-9 April 2014, Florence, Italy: A summary of topics and trends', SCHIZOPHRENIA RESEARCH, 159 E1-E22 (2014)
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2013 |
Manning EE, van den Buuse M, 'BDNF deficiency and young-adult methamphetamine induce sex-specific effects on prepulse inhibition regulation', Frontiers in Cellular Neuroscience, (2013) Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of schizophrenia, yet its role in the development of specific symptoms is unclear. Methamphetam... [more] Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of schizophrenia, yet its role in the development of specific symptoms is unclear. Methamphetamine (METH) users have an increased risk of psychosis and schizophrenia, and METH-treated animals have been used extensively as a model to study the positive symptoms of schizophrenia. We investigated whether METH treatment in BDNF heterozygous mutant mice (HET) has cumulative effects on sensorimotor gating, including the disruptive effects of psychotropic drugs. BDNF HETs and WT littermates were treated during young-adulthood with METH and, following a two-week break, prepulse inhibition (PPI) was examined. At baseline, BDNF HETs showed reduced PPI compared to WT mice irrespective of METH pre-treatment. An acute challenge with amphetamine (AMPH) disrupted PPI but male BDNF HETs were more sensitive to this effect, irrespective of METH pre-treatment. In contrast, female mice treated with METH were less sensitive to the disruptive effects of AMPH, and there were no effects of BDNF genotype. Similar changes were not observed in the response to an acute apomorphine or MK-801 challenge. These results show that genetically-induced reduction of BDNF caused changes in a behavioural endophenotype relevant to the positive symptoms of schizophrenia. However, major sex differences were observed in the effects of a psychotropic drug challenge on this behaviour. These findings suggest sex differences in the effects of BDNF depletion and METH treatment on the monoamine signaling pathways that regulate PPI. Given that these same pathways are thought to contribute to the expression of positive symptoms in schizophrenia, this work suggests that there may be significant sex differences in the pathophysiology underlying these symptoms. Elucidating these sex differences may be important for our understanding of the neurobiology of schizophrenia and developing better treatments strategies for the disorder. © 2013 Manning and Van_den_buuse.
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Show 18 more journal articles |
Conference (10 outputs)
Year | Citation | Altmetrics | Link |
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2021 | Geramita M, Manning E, Piantadosi S, Ahmari S, 'Degraded Encoding of Reversal Learning Resulting From Abnormal Grooming-Related LOFC Activity Normalizes After Fluoxetine Treatment in a Model of Compulsive Behavior', BIOLOGICAL PSYCHIATRY (2021) | ||
2020 | Geramita M, Manning E, Ahmari S, 'Influence of Fluoxetine on Perseverative Behavior-Related Activity in Lateral Orbitofrontal Cortex', BIOLOGICAL PSYCHIATRY, New York, NY (2020) | ||
2020 | Piantadosi S, Manning E, Brittany C, James H, Namboodiri VMK, Ahmari S, 'Assessing the Role of Direct and Indirect Pathway Projecting Spiny Projection Neurons in Compulsive Behavior', NEUROPSYCHOPHARMACOLOGY, ELECTR NETWORK (2020) | ||
Show 7 more conferences |
Preprint (8 outputs)
Year | Citation | Altmetrics | Link | |||||
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2024 |
Manning E, Crummy E, LaPalombara Z, Li X, Manikandan S, Ahmari S, '
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2023 |
Duchatel R, Jackson E, Parackal S, Sun C, Daniel P, Mannan A, et al., 'PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma (2023)
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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)
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Show 5 more preprints |
Grants and Funding
Summary
Number of grants | 10 |
---|---|
Total funding | $3,014,034 |
Click on a grant title below to expand the full details for that specific grant.
20234 grants / $1,840,263
A new mechanism for targeting stress-related mental health disorders$836,199
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Chris Dayas, Dr Jaideep Bains, Doctor Lizzie Manning |
Scheme | Ideas Grants |
Role | Investigator |
Funding Start | 2023 |
Funding Finish | 2026 |
GNo | G2200413 |
Type Of Funding | C1100 - Aust Competitive - NHMRC |
Category | 1100 |
UON | Y |
Striatal population involvement in OCD symptom domains$644,116
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Doctor Lizzie Manning, Assoicate Professor Susanne Ahmari, Susanne Ahmari |
Scheme | Ideas Grants |
Role | Lead |
Funding Start | 2023 |
Funding Finish | 2025 |
GNo | G2200412 |
Type Of Funding | C1100 - Aust Competitive - NHMRC |
Category | 1100 |
UON | Y |
Neural circuit control of effort under stress$314,477
Funding body: ARC (Australian Research Council)
Funding body | ARC (Australian Research Council) |
---|---|
Project Team | Doctor Lizzie Manning, Professor Chris Dayas, Doctor Susannah Tye |
Scheme | Discovery Projects |
Role | Lead |
Funding Start | 2023 |
Funding Finish | 2025 |
GNo | G2300155 |
Type Of Funding | C1200 - Aust Competitive - ARC |
Category | 1200 |
UON | Y |
Upgrade existing Inscopix miniature microscope for 2 colour system (nVue 2.0)$45,471
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Doctor Lizzie Manning |
Scheme | Equipment Grant |
Role | Lead |
Funding Start | 2023 |
Funding Finish | 2023 |
GNo | G2301084 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
20221 grants / $375,003
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 |
20212 grants / $292,768
Hypothalamic-basal ganglia circuit control of stress-induced repetitive behavior$183,834
Funding body: Tourette Association of America
Funding body | Tourette Association of America |
---|---|
Project Team | Doctor Lizzie Manning, Professor Chris Dayas, Chris Pittenger, Susanne Ahmari |
Scheme | TAA Young Investigator Award |
Role | Lead |
Funding Start | 2021 |
Funding Finish | 2023 |
GNo | G2001380 |
Type Of Funding | C3500 – International Not-for profit |
Category | 3500 |
UON | Y |
Understanding the link between fatigue and impairments in motivation$108,934
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Chris Dayas, Doctor Lizzie Manning |
Scheme | Research Grant |
Role | Investigator |
Funding Start | 2021 |
Funding Finish | 2021 |
GNo | G2101206 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
20201 grants / $100,000
Visualizing neuronal activity patterns associated with cognitive symptoms relevant to schizophrenia using in vivo microscopy$100,000
Funding body: Rebecca L Cooper Medical Research Foundation Ltd
Funding body | Rebecca L Cooper Medical Research Foundation Ltd |
---|---|
Project Team | Doctor Lizzie Manning |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2020 |
Funding Finish | 2022 |
GNo | G2000859 |
Type Of Funding | C1700 - Aust Competitive - Other |
Category | 1700 |
UON | Y |
20181 grants / $371,000
Using in vivo calcium imaging to differentiate prefrontal cortex activity underlying OCD-relevant impairments in cognitive flexibility and compulsive grooming$371,000
Funding body: National Institute of Mental Health (NIMH)
Funding body | National Institute of Mental Health (NIMH) |
---|---|
Project Team | Susanne Ahmari, Lizzie Manning |
Scheme | NIH Exploratory/Developmental Research Grant Award (R21) |
Role | Investigator |
Funding Start | 2018 |
Funding Finish | 2020 |
GNo | |
Type Of Funding | C3232 - International Govt - Other |
Category | 3232 |
UON | N |
20151 grants / $35,000
Sir Keith Murdoch Research Fellowship$35,000
Funding body: American Australian Association
Funding body | American Australian Association |
---|---|
Project Team | Lizzie Manning |
Scheme | Graduate Education Scholarships |
Role | Lead |
Funding Start | 2015 |
Funding Finish | 2016 |
GNo | |
Type Of Funding | C3212 - International Not for profit |
Category | 3212 |
UON | N |
Research Supervision
Number of supervisions
Current Supervision
Commenced | Level of Study | Research Title | Program | Supervisor Type |
---|---|---|---|---|
2023 | PhD | Investigating Interactions Between Stress and Action-Control Pathways Associated with Repetitive Behaviours in OCD and Tourette Syndrome | PhD (Human Physiology), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2023 | PhD | Resetting Hypothalamic circuits to Treat Depression | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2022 | PhD | How does Stress Impact Striatal Circuits involved in Behavioural Dysfunction Relevant to Stress-Related Neuropsychiatric Disorders | 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 |
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 | 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 |
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.
Dr Lizzie Manning
Position
Senior Lecturer Physiology
School of Biomedical Sciences and Pharmacy
College of Health, Medicine and Wellbeing
Contact Details
lizzie.manning@newcastle.edu.au | |
Phone | +61 2 4055 0154 |
Link |
Office
Room | MS506 |
---|