Professor Chris Dayas
School of Biomedical Sciences and Pharmacy (Anatomy)
- Phone:(02) 4921 5618
From neurons to networks to behaviour
A contemporary contributor to understandings of the central nervous system, Associate Professor Chris Dayas is proving – and, at times, disproving – ideas about the brain’s structure and its influence on motivation and emotion.
Mapping the brain is akin to playing Connect the Dots – without the helpful alphabetical and numerical hints. Indeed, in the neuroscience version, the large and obvious points are replaced by much smaller, microscopic cellular arrangements numbered in the billions, and the lines, though similarly serving to join each salient feature, represent the technical and nuanced instead of the sublimely superficial. It’s an almost incomprehensible maze of pathways telling us how and what and why and when we think and act, as intricate and delicate as the organ itself. Associate Professor Chris Dayas, an expert in this interdisciplinary field, is meeting this challenge head-on.
“My research focuses on the brain’s motivation and emotion centres,” he elaborates.
“While they are separate regions, they are highly interconnected and talk to each other.”
I’m interested in exploring these connections, right down to the molecular and cellular changes that occur.
Originally planning to pursue a childhood interest in marine biology, Chris credits several “inspiring” mentors for his rewarding and fruitful switch to neuroscience. Singling out high school teacher and marine biologist Ted Brambleby and university Professors Trevor Day and Janet Keast, the avid surfer and ocean enthusiast speaks of successful crossovers into psychiatry and public health as well.
“I’m passionate about finding better outcomes for pathologies of motivation and emotion, such as drug addiction and depression,” he asserts.
Before we can do this we need to gain a better understanding of the neuroanatomical and neurochemical interactions between key components of brain circuitry that are thought to be responsible for provoking relapse to these conditions.”
“Although much progress has been made in identifying individual brain regions that elicit reward-seeking behaviour, there are presently very few effective therapies available to treat pathological reward seeking – a core symptom of addiction and obesity – as well as depression, where the opposite occurs, you see low motivation and reward seeking.”
Chris’ research career began in 1997 when he undertook a PhD at the University of Queensland. Chiefly concentrating on the emotional side of the brain, the four-year probe sought to investigate how the brain responds to different types of stress.
“At the time, there was general consensus among scholars that the brain responds to all types of stress the same way,” he recalls.
“I identified, however, that psychological stresses, or ‘perceived threats’ important for the onset of neuropsychiatric conditions such as depression, activated a different part of the amygdala compared to physiological stresses, such as hypoxia and haemorrhage.”
“I found that psychological and physiological stress elicits distinct activity ‘footprints’ within this subcortical structure as well as sub-populations of catecholamine cells, like noradrenaline and dopamine cells within the brainstem.”
A stubborn problem
Awarded a prestigious CJ Martin Fellowship from the National Health and Medical Research Council (NHMRC) after receiving his award in 2001, Chris relocated to the United States to undertake postdoctoral training at The Scripps Research Institute. Principally focusing on alcohol addiction, the 2002-2006 stint in California’s sunny and surf capital ended up “intellectually fusing” two of the Brisbane native’s primary interests.
“The parts of the brain that deal with stress connect to the hypothalamus, which reacts to drug abuse,” he explains.
“I endeavoured to bring these two interests together.”
Aspiring to help build a solid knowledge base around the neural pathways that control reinstatement of alcohol relapse, Chris published his overseas findings in the high profile journals Biological Psychiatry and the Journal of Neuroscience.
“We showed that cells in the hypothalamus, which people used to think were important solely in food-seeking, are involved in drug addiction too,” he reveals.
“Hypothalamic peptide systems, better known for their role in feeding behaviour, may therefore be significant neurotransmitters in the brain circuitry that trigger alcohol-seeking behaviour.”
“We’re still studying them very closely.”
Creative and scientific in equal measure, Chris employed a number of different methods to shed light on these connections.
“We used antibodies to bind to the cells and immunofluorescence to look at their structure,” he shares.
“Markers of activity were also established to help analyse how the cells changed over time.”
“I was lucky enough to work with Associate Professor Brett Graham, an electrophysiologist, and Dr Doug Smith, a molecular biologist, as well.”
Chris moved to the University of Newcastle in 2007 to set up his own laboratory in the Discipline of Anatomy, School of Biomedical Sciences and Pharmacy where he continues to examine the role of hypothalamic peptides in driving drug-seeking and relapse-like behaviour.
“I received a generous grant from the NHMRC to commence this work,” he states.
“We’re applying new, cutting-edge techniques to see how cellular connections alter following drug abuse or chronic stress.”
Referring particularly to optogenetics, which involves the use of light to control cells in living tissue, Chris believes these new “genetic tricks” will quickly advance our understanding of the brain, and hopefully identify new treatments.
“My group is using this process of inserting light-activatable proteins from algae into various types of brain cells,” he discloses.
“This will allow us to experimentally ‘shine a light’ on connections between different parts of the brain.”
“Glencore recently awarded us a philanthropic grant to buy a specialised ‘optogenetics’ microscope specifically designed for such a purpose.”
“It’s in its early days but we’re getting some fascinating results.”
My post-doctoral research at The Scripps Research Institute contributed to the understanding of the neural pathways that control reinstatement of alcohol relapse. In articles published in the journal Biological Psychiatry and Journal of Neuroscience, I showed that the pattern of neural activity elicited by stimuli conditioned to predict the availability of alcohol, a factor linked to increased relapse risk in humans, is similar to the patterns produced by stimuli paired with the availability of other commonly abused drugs such as cocaine or nicotine. Additionally, we demonstrated how existing neuropharmacological treatments for alcoholism such as naltrexone, or newer agents that show promise in the treatment of addiction such as agonists for group II/III metabotropic glutamate (mGlu2/3) receptors, also modulate these patterns. We also showed that mGlu2/3 receptor agonists, which appear to have an anxiolytic profile, are effective in suppressing reinstatement (or relapse) elicited by stress - an important trigger for relapse in humans.
At Scripps I also demonstrated that hypothalamic peptide systems, better known for their role in feeding behaviour, may be important neurotransmitters in the brain circuitry that trigger alcohol seeking behaviour.
After returning to Australia, I established my own laboratory in the Discipline of Anatomy, School of Biomedical Sciences and Pharmacy, University of Newcastle to investigate the role of these hypothalamic peptides in driving drug-seeking and relapse-like behaviour. I received an NHMRC grant in to commence this work. My laboratory therefore focuses on the brain pathways that are involved in addiction and stress.
Relapse to drug taking is considered the most significant obstacle to the successful treatment of addiction. Although much progress has been made in identifying individual brain regions that elicit drug-seeking behaviour and subsequently relapse, there are presently very few effectively pharmaceutical or indeed behavioural therapy strategies available to treat this disease. My research interests concern the following key issues: 1.Understanding the neuroanatomical and pharmacological interactions between key components of brain circuitry thought to be responsible for provoking drug relapse. 2.Determining the role of the neuropeptides (orexin/hypocretin and CART) recently found to be powerful modulators of drug-seeking and relapse. 3.Elucidating the cellular and molecular neuroadaptations that promotes long-term relapse vulnerability. 4.Determining the neurobiological basis for why some individuals become addicted and show greater vulnerability to drug relapse than others.
Relapse to drug taking is considered the most significant obstacle to the successful treatment of addiction. Although much progress has been made in identifying individual brain regions that elicit drug-seeking behaviour and subsequently relapse, there are presently very few effectively pharmaceutical or indeed behavioural therapy strategies available to treat this disease. My research interests concern the following key issues: 1. Understanding the neuroanatomical and pharmacological interactions between key components of brain circuitry thought to be responsible for provoking drug relapse. 2. Determining the role of the neuropeptides (orexin/hypocretin and CART) recently found to be powerful modulators of drug-seeking and relapse. 3. Elucidating the cellular and molecular neuroadaptations that promotes long-term relapse vulnerability. 4. Determining the neurobiological basis for why some individuals become addicted and show greater vulnerability to drug relapse than others.
- PhD, University of Queensland
- Bachelor of Science (Honours), University of Queensland
Fields of Research
|110999||Neurosciences not elsewhere classified||100|
|Title||Organisation / Department|
|Professor||University of Newcastle
School of Biomedical Sciences and Pharmacy
|Dates||Title||Organisation / Department|
|1/11/2006 - 1/12/2008||
CJ Martin Biomedical Fellowships (Overseas)
NHMRC - Early Career Fellowships (Formerly Postdoctoral Training Fellowships)
|National Health & Medical Research Council|
|Dates||Title||Organisation / Department|
|Member - Society for Neuroscience||Society for Neuroscience
|Member - Australian Neuroscience Society||Australian Neuroscience Society (ANS)
|Member - Research Society on Alcoholism||Research Society on Alcoholism
|Year||Title / Rationale|
" Invited speaker at the Research Society on Alcoholism Meeting in Vancouver, Canada, 2004
Organisation: Research Society on Alcholism
For publications that are currently unpublished or in-press, details are shown in italics.
Chapter (2 outputs)
James MH, Campbell EJ, Dayas CV, 'Role of the Orexin/Hypocretin system in stress-related psychiatric disorders', Behavioral Neuroscience of Orexin/Hypocretin, Springer, New York 197-219 (2017) [B1]
Caille S, Baker AL, Todd J, Turner A, Dayas CV, 'Smoking and mental health problems', The Tobacco Epidemic, S. Karger AG, Basel, Switzerland 199-209 (2015) [B1]
Journal article (49 outputs)
Skinner JA, Garg ML, Dayas CV, Burrows TL, 'Using participant ratings to construct food image paradigms for use in the Australian population A pilot study', Food Quality and Preference, 82 (2020)
© 2020 In human research, images of food are often used as cues in place of real foods. To elicit anticipatory responses in targeted populations (e.g. prompting changes in metabol... [more]
© 2020 In human research, images of food are often used as cues in place of real foods. To elicit anticipatory responses in targeted populations (e.g. prompting changes in metabolic hormones, invoking food cravings), cultural differences and population norms with regard to food preferences need to be considered. This pilot study aimed to construct two image paradigms (healthy vs. hyperpalatable foods) for experimental use within the Australian population. A dataset of 200 images (from the licenced database Food-pics and internet sources), representative of healthy and hyperpalatable foods commonly consumed in Australia, was compiled by research dietitians. Ten male and female adults volunteered to view the images. Participants categorised each image as either healthy food or ¿junk food¿ (i.e. hyperpalatable food), and rated each image according to three criteria: 1) familiarity of the food displayed; 2) recognisability of the food; and 3) appetisingness of the food. Overall, agreement with a priori categories was high for both healthy and hyperpalatable food images, 87.3% and 87.7% respectively. The food images with the lowest overall ratings (score <7 out of possible 9) were removed from the dataset and the final paradigms each contain 75 images. The healthy food paradigm contains foods from the five core food groups (fruit, vegetables, grains and cereals, meat and meat alternatives, dairy foods), and the hyperpalatable food paradigm contains non-core foods (sweet and savoury discretionary choice foods). The paradigms represent a broad range of commonly consumed foods that will be relevant for prospective projects utilising food cues in Australian adults.
Skinner JA, Garg ML, Dayas CV, Burrows TL, 'Is weight status associated with peripheral levels of oxytocin? A pilot study in healthy women.', PHYSIOLOGY & BEHAVIOR, 212 (2019) [C1]
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]
© 2018 The perifornical/lateral hypothalamic area (LHA) orexin (hypocretin) system is involved in drug-seeking behavior elicited by drug-associated stimuli. Cocaine exposure is as... [more]
© 2018 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¿.
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)
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]
© 2019 Elsevier Inc. Neuropeptide Y (NPY) exerts a powerful orexigenic effect in the hypothalamus. However, extra-hypothalamic nuclei also produce NPY, but its influence on energy... [more]
© 2019 Elsevier Inc. 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.
Skinner JA, Campbell EJ, Dayas CV, Garg ML, Burrows TL, 'The relationship between oxytocin, dietary intake and feeding: A systematic review and meta-analysis of studies in mice and rats', Frontiers in Neuroendocrinology, 52 65-78 (2019) [C1]
© 2018 Elsevier Inc. The neuropeptide oxytocin has been associated with food intake and feeding behaviour. This systematic review aimed to investigate the impact of oxytocin on di... [more]
© 2018 Elsevier Inc. The neuropeptide oxytocin has been associated with food intake and feeding behaviour. This systematic review aimed to investigate the impact of oxytocin on dietary intake and feeding behaviour in rodent studies. Six electronic databases were searched to identify published studies to April 2018. Preclinical studies in mice and rats were included if they reported: (1) a dietary measure (i.e. food or nutrient and/or behaviour (2) an oxytocin measure, and (3) relationship between the two measures. A total of 75 articles (n = 246 experiments) were included, and study quality appraised. The majority of studies were carried out in males (87%). The top three oxytocin outcomes assessed were: exogenous oxytocin administration (n = 126), oxytocin-receptor antagonist administration (n = 46) and oxytocin gene deletion (n = 29). Meta-analysis of exogenous studies in mice (3 studies, n = 43 comparisons) and rats (n = 8 studies, n = 82 comparisons) showed an overall decrease in food intake with maximum effect shown at 2 h post-administration.
Skinner JA, Garg ML, Dayas CV, Fenton S, Burrows TL, 'Relationship between dietary intake and behaviors with oxytocin: a systematic review of studies in adults.', Nutr Rev, 76 303-331 (2018) [C1]
Quinn RK, James MH, Hawkins GE, Brown AL, Heathcote A, Smith DW, et al., 'Temporally specific miRNA expression patterns in the dorsal and ventral striatum of addiction-prone rats', Addiction Biology, 23 631-642 (2018) [C1]
© 2017 Commonwealth of Australia. Addiction Biology © 2017 Society for the Study of Addiction MicroRNAs (miRNAs) within the ventral and dorsal striatum have been shown to regulate... [more]
© 2017 Commonwealth of Australia. Addiction Biology © 2017 Society for the Study of Addiction MicroRNAs (miRNAs) within the ventral and dorsal striatum have been shown to regulate addiction-relevant behaviours. However, it is unclear how cocaine experience alone can alter the expression of addiction-relevant miRNAs within striatal subregions. Further, it is not known whether differential expression of miRNAs in the striatum contributes to individual differences in addiction vulnerability. We first examined the effect of cocaine self-administration on the expression of miR-101b, miR-137, miR-212 and miR-132 in nucleus accumbens core and nucleus accumbens shell (NAcSh), as well as dorsomedial striatum and dorsolateral striatum (DLS). We then examined the expression of these same miRNAs in striatal subregions of animals identified as being ¿addiction-prone¿, either immediately following self-administration training or following extinction and relapse testing. Cocaine self-administration was associated with changes in miRNA expression in a regionally discrete manner within the striatum, with the most marked changes occurring in the nucleus accumbens core. When we examined the miRNA profile of addiction-prone rats following self-administration, we observed increased levels of miR-212 in the dorsomedial striatum. After extinction and relapse testing, addiction-prone rats showed significant increases in the expression of miR-101b, miR-137, miR-212 and miR-132 in NAcSh, and miR-137 in the DLS. This study identifies temporally specific changes in miRNA expression consistent with the engagement of distinct striatal subregions across the course of the addiction cycle. Increased dysregulation of miRNA expression in NAcSh and DLS at late stages of the addiction cycle may underlie habitual drug seeking, and may therefore aid in the identification of targets designed to treat addiction.
Burrows T, Kay-Lambkin F, Pursey K, Skinner J, Dayas C, 'Food addiction and associations with mental health symptoms: a systematic review with meta-analysis', Journal of Human Nutrition and Dietetics, 31 544-572 (2018) [C1]
© 2018 The British Dietetic Association Ltd. Background: The present study systematically reviewed the literature aiming to determine the relationships between food addiction, as ... [more]
© 2018 The British Dietetic Association Ltd. Background: The present study systematically reviewed the literature aiming to determine the relationships between food addiction, as measured by the Yale Food Addiction Scale (YFAS), and mental health symptoms. Methods: Nine databases were searched using keywords. Studies were included if they reported: (i) YFAS diagnosis or symptom score and (ii) a mental health outcome, as well as the association between (i) and (ii). In total, 51 studies were included. Results: Through meta-analysis, the mean prevalence of food addiction diagnosis was 16.2%, with an average of 3.3 (range 2.85¿3.92) food addiction symptoms being reported. Subanalyses revealed that the mean number of food addiction symptoms in populations seeking treatment for weight loss was 3.01 (range 2.65¿3.37) and this was higher in groups with disordered eating (mean 5.2 3.6¿6.7). Significant positive correlations were found between food addiction and binge eating [mean r¿=¿0.602 (0.557¿0.643), P¿<¿0.05], depression, anxiety and food addiction [mean r¿=¿0.459 (0.358¿0.550), r¿=¿0.483 (0.228¿0.676), P¿<¿0.05, respectively]. Conclusions: A significant, positive relationship exists between food addiction and mental health symptoms, although the results of the present study highlight the complexity of this relationship.
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]
© 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd Altered motivated behaviour is a cardinal feature of several neuropsychiatric conditions inclu... [more]
© 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd 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.
Campbell EJ, Barker DJ, Nasser HM, Kaganovsky K, Dayas CV, Marchant NJ, 'Cue-induced food seeking after punishment is associated with increased fos expression in the lateral hypothalamus and basolateral and medial amygdala', Behavioral Neuroscience, 131 155-167 (2017) [C1]
© 2017 American Psychological Association. In humans, relapse to unhealthy eating habits following dieting is a significant impediment to obesity treatment. Food-associated cues a... [more]
© 2017 American Psychological Association. In humans, relapse to unhealthy eating habits following dieting is a significant impediment to obesity treatment. Food-associated cues are one of the main triggers of relapse to unhealthy eating during self-imposed abstinence. Here we report a behavioral method examining cue-induced relapse to food seeking following punishment-induced suppression of food taking. We trained male rats to lever press for food pellets that were delivered after a 10-s conditional stimulus (CS) (appetitive). Following training, 25% of reinforced lever presses resulted in the presentation of a compound stimulus consisting of a novel CS (aversive) and the appetitive CS followed by a pellet and footshock. After punishment-imposed abstinence, we tested the rats in an extinction test where lever pressing resulted in the presentation of either the appetitive or aversive CS. We then compared activity of lateral hypothalamus (LH) and associated extrahypothalamic regions following this test. We also assessed Fos expression in LH orexin and GABA neurons. We found that cue-induced relapse of food seeking on test was higher in rats tested with the appetitive CS compared to the aversive CS. Relapse induced by the appetitive CS was associated with increased Fos expression in LH, caudal basolateral amygdala (BLA), and medial amygdala (MeA). This relapse was also associated with increased Fos expression in LH orexin and VGAT-expressing neurons. These data show that relapse to food seeking can be induced by food-associated cues after punishment-imposed abstinence, and this relapse is associated with increased activity in LH, caudal BLA, and MeA.
Burrows T, Hides L, Brown R, Dayas CV, Kay-Lambkin F, 'Differences in Dietary Preferences, Personality and Mental Health in Australian Adults with and without Food Addiction', NUTRIENTS, 9 (2017) [C1]
Parkinson GM, Dayas CV, Smith DW, 'Perturbed cholesterol homeostasis in aging spinal cord', Neurobiology of Aging, 45 123-135 (2016) [C1]
© 2016 Elsevier Inc. The spinal cord is vital for the processing of sensorimotor information and for its propagation to and from both the brain and the periphery. Spinal cord func... [more]
© 2016 Elsevier Inc. The spinal cord is vital for the processing of sensorimotor information and for its propagation to and from both the brain and the periphery. Spinal cord function is affected by aging, however, the mechanisms involved are not well-understood. To characterize molecular mechanisms of spinal cord aging, microarray analyses of gene expression were performed on cervical spinal cords of aging rats. Of the metabolic and signaling pathways affected, cholesterol-associated pathways were the most comprehensively altered, including significant downregulation of cholesterol synthesis-related genes and upregulation of cholesterol transport and metabolism genes. Paradoxically, a significant increase in total cholesterol content was observed-likely associated with cholesterol ester accumulation. To investigate potential mechanisms for the perturbed cholesterol homeostasis, we quantified the expression of myelin and neuroinflammation-associated genes and proteins. Although there was minimal change in myelin-related expression, there was an increase in phagocytic microglial and astrogliosis markers, particularly in the white matter. Together, these results suggest that perturbed cholesterol homeostasis, possibly as a result of increased inflammatory activation in spinal cord white matter, may contribute to impaired spinal cord function with aging.
James MH, Quinn RK, Ong LK, Levi EM, Smith DW, Dickson PW, Dayas CV, 'Rapamycin reduces motivated responding for cocaine and alters GluA1 expression in the ventral but not dorsal striatum', European Journal of Pharmacology, 784 147-154 (2016) [C1]
© 2016 Published by Elsevier B.V. All rights reserved. The mechanistic target of rapamycin complex 1 (mTORC1) regulates synaptic protein synthesis and therefore synaptic function ... [more]
© 2016 Published by Elsevier B.V. All rights reserved. The mechanistic target of rapamycin complex 1 (mTORC1) regulates synaptic protein synthesis and therefore synaptic function and plasticity. A role for mTORC1 has recently been demonstrated for addiction-related behaviors. For example, central or intra-accumbal injections of the mTORC1 inhibitor rapamycin attenuates several indices of cocaine-seeking including progressive ratio (PR) responding and reinstatement. These behavioral effects are associated with decreased mTORC1 activity and synaptic protein translation in the nucleus accumbens (NAC) and point to a possible therapeutic role for rapamycin in the treatment of addiction. Currently, it is unclear whether similar behavioral and biochemical effects can be achieved by administering rapamycin systemically, which represents a more clinically-appropriate route of administration. Here, we assessed the effects of repeated, systemic administration of rapamycin (10 mg/kg, i.p.) on PR responding for cocaine. We also assessed whether systemic rapamycin was associated with changes in measures of mTORC1 activity and GluA1 expression in the ventral and dorsal striatum. We report that systemic rapamycin treatment reduced PR breakpoints to levels comparable to intra-NAC rapamycin. Systemic rapamycin treatment also reduced phosphorylated p70S6K and GluA1 AMPARs within the NAC but not dorsal striatum. Thus, systemic administration of rapamycin is as effective at reducing drug seeking behavior and measures of mTORC1 activity compared to direct accumbal application and may therefore represent a possible therapeutic option in the treatment of addiction. Possible caveats of this treatment approach are discussed.
Quinn RK, Brown AL, Goldie BJ, Levi EM, Dickson PW, Smith DW, et al., 'Distinct miRNA expression in dorsal striatal subregions is associated with risk for addiction in rats', Translational Psychiatry, 5 (2015) [C1]
Recently, we published data using an animal model that allowed us to characterize animals into two groups, addiction vulnerable and addiction resilient, where we identified that a... [more]
Recently, we published data using an animal model that allowed us to characterize animals into two groups, addiction vulnerable and addiction resilient, where we identified that addiction/relapse vulnerability was associated with deficits in synaptic plasticityassociated gene expression in the dorsal striatum (DS). Notable was the strong reduction in expression for activity-regulated cytoskeleton-associated protein (Arc) considered a master regulator of synaptic plasticity. In the present study, we confirmed that Arc messenger RNA was significantly decreased in the DS, but importantly, we identified that this reduction was restricted to the dorsomedial (DMS) and not dorsolateral striatum (DLS). There is recent evidence of microRNA (miRNA)-associated posttranscriptional suppression of Arc and animal models of addiction have identified a key role for miRNA in the regulation of addiction-relevant genes. In further support of this link, we identified several differentially expressed miRNA with the potential to influence addiction-relevant plasticity genes, including Arc. A key study recently reported that miR-212 expression is protective against compulsive cocaine-seeking. Supporting this hypothesis, we found that miR-212 expression was significantly reduced in the DMS but not DLS of addiction-vulnerable animals. Together, our data provide strong evidence that miRNA promote ongoing plasticity deficits in the DS of addiction-vulnerable animals.
Campbell EJ, Watters SM, Zouikr I, Hodgson DM, Dayas CV, 'Recruitment of hypothalamic orexin neurons after formalin injections in adult male rats exposed to a neonatal immune challenge', Frontiers in Neuroscience, 9 (2015) [C1]
© 2015 Campbell, Watters, Zouikr, Hodgson and Dayas. Exposure to early life physiological stressors, such as infection, is thought to contribute to the onset of psychopathology in... [more]
© 2015 Campbell, Watters, Zouikr, Hodgson and Dayas. Exposure to early life physiological stressors, such as infection, is thought to contribute to the onset of psychopathology in adulthood. In animal models, injections of the bacterial immune challenge, lipopolysaccharide (LPS), during the neonatal period has been shown to alter both neuroendocrine function and behavioural pain responses in adulthood. Interestingly, recent evidence suggests a role for the lateral hypothalamic peptide orexin in stress and nociceptive processing. However, whether neonatal LPS exposure affects the reactivity of the orexin system to formalin-induced inflammatory pain in later life remains to be determined. Male Wistar rats (n=13) were exposed to either LPS or saline (0.05mg/kg, i.p) on postnatal days (PND) 3 and 5. On PND 80-97, all rats were exposed to a subcutaneous hindpaw injection of 2.25% formalin. Following behavioural testing, animals were perfused and brains processed for Fos-protein and orexin immunohistochemistry. Rats treated with LPS during the neonatal period exhibited decreased licking behaviours during the interphase of the formalin test, the period typically associated with the active inhibition of pain, and increased grooming responses to formalin in adulthood. Interestingly, these behavioural changes were accompanied by an increase in the percentage of Fos-positive orexin cells in the dorsomedial and perifornical hypothalamus in LPS-exposed animals. Similar increases in Fos-protein were also observed in stress and pain sensitive brain regions that receive orexinergic inputs. These findings highlight a potential role for orexin in the behavioural responses to pain and provide further evidence that early life stress can prime the circuitry responsible for these responses in adulthood.
Parkinson GM, Dayas CV, Smith DW, 'Age-related gene expression changes in substantia nigra dopamine neurons of the rat.', Mech Ageing Dev, 149 41-49 (2015) [C1]
James MH, Quinn RK, Ong LK, Levi EM, Charnley JL, Smith DW, et al., 'mTORC1 inhibition in the nucleus accumbens 'protects' against the expression of drug seeking and 'relapse' and is associated with reductions in GluA1 AMPAR and CAMKIIa levels.', Neuropsychopharmacology, 39 1694-1702 (2014) [C1]
Goldie BJ, Dun MD, Lin M, Smith ND, Verrills NM, Dayas CV, Cairns MJ, 'Activity-associated miRNA are packaged in Map1b-enriched exosomes released from depolarized neurons.', Nucleic Acids Research, 42 9195-9208 (2014) [C1]
Parkinson GM, Dayas CV, Smith DW, 'Increased mitochondrial DNA deletions in substantia nigra dopamine neurons of the aged rat.', Current aging science, 7 155-160 (2014) [C2]
Zouikr I, James MH, Campbell EJ, Clifton VL, Beagley KW, Dayas CV, Hodgson DM, 'Altered formalin-induced pain and fos induction in the periaqueductal grey of preadolescent rats following neonatal LPS exposure', PLoS ONE, 9 (2014) [C1]
Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanic... [more]
Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supraspinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG) as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb) as compared to medial habenula (MHb), however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process. © 2014 Zouikr et al.
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]
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]
James MH, Campbell EJ, Walker FR, Smith DW, Richardson HN, Hodgson DM, Dayas CV, 'Exercise reverses the effects of early life stress on orexin cell reactivity in male but not female rats', Frontiers in Behavioral Neuroscience, 8 (2014) [C1]
James MH, Dayas CV, 'What about me ...? The PVT: a role for the paraventricular thalamus (PVT) in drug-seeking behavior', FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 7 (2013) [C3]
Cahif A, Parkinson GM, Dayas CV, Smith DW, 'Characterisation of mitochondrial DNA deletions by long-PCR in central nervous system regions of young, middle- and old-aged rats.', Current Aging Science, 6 232-238 (2013) [C1]
Brown AL, Day TA, Dayas CV, Smith DW, 'Purity and Enrichment of Laser-Microdissected Midbrain Dopamine Neurons', BIOMED RESEARCH INTERNATIONAL, (2013) [C1]
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]
Dayas CV, Smith DW, Dunkley PR, 'An emerging role for the mammalian Target of Rapamycin (mTOR) in 'pathological' protein translation: Relevance to cocaine addiction', Frontiers in Pharmacology, 3 1-12 (2012) [C1]
James MH, Charnley JL, Flynn JR, Smith DW, Dayas CV, 'Propensity to 'relapse' following exposure to cocaine cues is associated with the recruitment of specific thalamic and epithalamic nuclei', Neuroscience, 199 235-242 (2011) [C1]
James MH, Charnley JL, Levi EM, Jones E, Yeoh JW, Smith DW, Dayas CV, 'Orexin-1 receptor signalling within the ventral tegmental area, but not the paraventricular thalamus, is critical to regulating cue-induced reinstatement of cocaine-seeking', International Journal of Neuropsychopharmacology, 14 684-690 (2011) [C1]
Brown AL, Flynn JR, Smith DW, Dayas CV, 'Down-regulated striatal gene expression for synaptic plasticity-associated proteins in addiction and relapse vulnerable animals', International Journal of Neuropsychopharmacology, 14 1099-1110 (2011) [C1]
James MH, Charnley JL, Jones E, Levi E, Yeoh JW, Flynn JR, et al., 'Cocaine- and amphetamine-regulated transcript (CART) signaling within the paraventricular thalamus modulates cocaine-seeking behaviour', Plos One, 5 e12980 (2010) [C1]
Martin-Fardon R, Baptista MAS, Dayas CV, Weiss F, 'Dissociation of the effects of MTEP [3-[(2-methyl-1,3-thiazol-4-yl)ethynyl] piperidine] on conditioned reinstatement and reinforcement: Comparison between cocaine and a conventional reinforcer', Journal of Pharmacology and Experimental Therapeutics, 329 1084-1090 (2009) [C1]
|Show 46 more journal articles|
Conference (11 outputs)
James MH, Charnley JL, Levi EM, Dunkley PR, Smith DW, Dickson PW, Dayas CV, 'A role for the mTOR pathway in the development of addiction', Abstracts. Australian Neuroscience Society 32nd Annual Meeting, Gold Coast, Queensland (2012) [E3]
Brown AL, Flynn JR, Dayas CV, Smith DW, 'Altered gene expression in cell signalling pathways of midbrain dopamine neurons from addiction and relapse vulnerable animals', Drug and Alcohol Review: Abstracts of the Australasian Professional Society on Alcohol and other Drugs Conference 2012, Melbourne, Vic (2012) [E3]
Dayas CV, Quinn RK, Goldie BJ, Brown AM, Levi EM, Smith DW, Cairns MJ, 'Association of miRNAs with addiction-relevant synaptic plasticity genes', Abstract Book. Biological Psychiatry Australia Scientific Meeting, Parkville, Vic (2012) [E3]
Campbell EJ, James MH, Sominsky Bar L, Hodgson DM, Dayas CV, 'Adult stress unmasks altered orexin cell functioning in maternally separated rats: Implications for the development of psychopathologies', Abstract Book. Biological Psychiatry Australia Scientific Meeting, Parkville, Vic (2012) [E3]
|2008||Dayas CV, 'The neurobiology of drug relapse: A role for hypothalamic 'feeding' peptides in drug relapse?', Australian and New Zealand Journal of Psychiatry, Newcastle, NSW (2008) [E3]|
|2007||Dayas CV, McGranahan TM, Martin-Fardon R, Weiss F, 'Hypothalamic feeding-related peptides are recruited in a reinstatement model of ethanol relapse (Poster)', 7th IBRO 2007 World Congress of Neuroscience Program, Melbourne (2007) [E3]|
|Show 8 more conferences|
Number of supervisions
|Commenced||Level of Study||Research Title||Program||Supervisor Type|
|2019||PhD||Development of a Multilevel Analgesic Screening Approach Using Optogenetics to Activate and Study Pain Pathways||PhD (Human Physiology), Faculty of Health and Medicine, The University of Newcastle||Co-Supervisor|
|2019||PhD||Modelling Genomic Variation in Complex Neurobehavioural Syndromes Using RNA-Guided Genome Editing in the Rat||PhD (Medical Genetics), Faculty of Health and Medicine, The University of Newcastle||Co-Supervisor|
|2019||PhD||Artificial Intelligence as an Enabling Technology in HealthCare - AOD Sector Analysis plus Digital Capability Development||PhD (Public Health & BehavSci), Faculty of Health and Medicine, The University of Newcastle||Co-Supervisor|
|2019||PhD||Investigating the Role of Striatal D1 and D2 Medium Spiny Neurons in the Transition to Compulsive Drug Seeking Behaviour||PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2019||PhD||Shedding New Light on How Projection Neurons Regulate Pain Signalling in the Spinal Cord and Brain||PhD (Human Physiology), Faculty of Health and Medicine, The University of Newcastle||Co-Supervisor|
|2019||PhD||Understanding the Impact of Addictive Drugs on Stress Circuits||PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2018||PhD||Personalised Genomics of Schizophrenia||PhD (Medical Genetics), Faculty of Health and Medicine, The University of Newcastle||Co-Supervisor|
|2018||PhD||Exploration of the Molecular Determinants of Comorbid Addiction in Schizophrenia||PhD (Medical Genetics), Faculty of Health and Medicine, The University of Newcastle||Co-Supervisor|
|2017||PhD||Investigation of Cellular and Molecular Mechanisms by which Iron Accumulation May Increase Susceptibility to Degenerative Brain Diseases||PhD (Medical Genetics), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2016||PhD||Characterising how Chronic Stress and Natural Rewards Impact Lateral Hypothalamic Circuitry||PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2016||PhD||Investigating objective biomarkers to characterise addictive eating||PhD (Nutrition & Dietetics), Faculty of Health and Medicine, The University of Newcastle||Co-Supervisor|
|2014||PhD||Procedures for Manipulating the Speed-Accuracy Trade-Off||PhD (Psychology - Science), Faculty of Science, The University of Newcastle||Co-Supervisor|
|Year||Level of Study||Research Title||Program||Supervisor Type|
|2018||PhD||Channelrhodopsin-Assisted Circuit Mapping of Medial Amygdaloid Connectivity to the Paraventricular Nucleus of the Hypothalamus||PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2016||PhD||Ageing of the Somatic Motor Nervous System: A Nuclear and Mitochondrial Genome Perspective||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Co-Supervisor|
|2016||PhD||Understanding Striatal Neuroadaptations in Addiction-Relapse Vulnerability||PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2016||PhD||Characterizing Changes in the Orexin System in Models of Neuropsychiatric Disease||PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2015||PhD||Drug-induced Changes to the Lateral Hypothalamic Circuits and Downstream Projection Targets||PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2015||PhD||Roles of Post-Transcriptional Gene Silencing in the Functional Regulation of Neuronal Gene Expression and Plasticity||PhD (Medical Biochemistry), Faculty of Health and Medicine, The University of Newcastle||Co-Supervisor|
|2014||PhD||The Role of Cocaine- and Amphetamine-Regulated Transcript (CART) and Orexin in Drug-Seeking and Addiction-Related Behaviours||PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle||Principal Supervisor|
|2012||PhD||Molecular Correlates of Dopamine Signalling in Addiction Vulnerability||PhD (Anatomy), Faculty of Health and Medicine, The University of Newcastle||Co-Supervisor|
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|
December 12, 2018
April 18, 2018
April 30, 2015
Professor Chris Dayas
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine