Translational Neuroscience Research Group – Closing the Gap
The conversion of promising findings from the research laboratory into effective clinical treatments for neurodegenerative and neuropsychiatric illnesses is very challenging. One element of the process that can be improved is the capability to readily translate between the assessments used to evaluate the effects of a potential therapeutic intervention on cognitive processes in model systems and those used in patients.
Recent developments in touchscreen computing have enabled the generation of a new approach to cognitive assessment based on the presentation of and interaction with sequences of visual stimuli that can be readily administered across model systems and clinical populations.
A major objective of the laboratory is the application of this approach to various models of neurodegenerative and neuropsychiatric illness and corresponding clinical populations to provide a consistent platform for model validation and novel therapeutic screening. The group is also working to develop, optimise and validate new touchscreen-based assessments to enable the study of additional cognitive domains with a focus on motivation, cost-benefit decision making and emotional state regulation. Another goal is to apply the technical and procedural advantages of this methodology to non-disease related areas, including routine welfare monitoring and circadian rhythm biology.
Current research in the group includes:
Chris Heath (Group Leader – Lecturer in Health Sciences)
Emily Breese (PhD student)
Peter Carr (Visiting undergraduate; December 2016)
Cheryl Hawkes and Laura Contu
Martin Thirkettle, Sheffield Hallam University
Claire O’Callaghan, University of Cambridge
Laura Lopez-Cruz, University of Cambridge
Ben Phillips, University of Cambridge
Tim Bussey and Lisa Saksida, University of Western Ontario, Canada
Eosu Kim, Yonsei University, Korea
|Role||Start date||End date||Funding source|
|Co-investigator||29 Mar 2021||28 Mar 2022||The Royal Society|
Major obstacles to the effective exploration of mood-related processes in neuropsychiatric illness include the lack of animal models that comprehensively recapitulate human presentation, the limited number of assessment tools to evaluate affective state in non-human species and, where such tools do exist, the lack of similarity between them and the methods used in the clinic or in human research. However, recent research has suggested that commonality in a construct referred to as ‘Cognitive Affective Bias’ (CAB) exists between species and behavioural tasks for assessing it have been developed and used as new approach for antidepressant screening in rodents. The basis of CAB concerns the way a subject interprets ambiguous/uncertain stimuli in their environment given their overall affective state. For example, people with anxiety or scoring high in the personality trait neuroticism show pessimistic cognitive bias when presented with ambiguous situations or stimuli (e.g. neutral faces). The identification of population with maladaptive cognitive biases is relevant since have shown to be central to the development and maintenance of depression. On the contrary, optimistic cognitive biases contributes to resilience to depression in humans and correlate with high motivation in both humans and animals. The study of CAB in animals could be used not only as a behavioural platform for antidepressant testing, also to identify individual pessimistic or optimistic-like tendencies, how they correlate with other behaviours and how they are regulated by different neurobiological substrates. The study of individual differences on CABs together with the assessment of other relevant behaviours would also contribute to characterise behavioural phenotypes which may be related with differences on sensitivity to manipulations known by inducing depression-like behaviour. In our lab we developed a touchscreen-based cognitive bias in mice which demonstrated to be sensitive to antidepressant and pro-depressant manipulations and which is currently being forward-translated to humans thanks to the translational potential of touchscreen devises. The present project aims 1) to study individual differences on CAB in mice and explore potential correlations with other relevant behaviours which have shown to correlate with pessimistic or optimistic biases in humans, such us motivation and anxiety, 2) if necessary, to optimise our CAB task to maximise individual differences to stablish a clear “cut off” to classify two types of populations (i.e. ‘optimistic’ vs. ‘pessimistic’ animals) and 3) to study patterns of neuronal activation by cFos in different brain areas known by being involved in the processing of affective information in both populations of mice. The results from this project will contribute to identify the target brain areas for the future analysis of specific mechanisms underlying vulnerability to depression as well as to optimise a touchscreen-based platform for the study of vulnerability to depression with a high translational potential.
|Role||Start date||End date||Funding source|
|Co-investigator||05 Oct 2018||04 Sep 2019||The Royal Society|
Self-administration models of addiction typically require animals to make the same response over and over to procure and take drugs. By their design, such procedures often produce behaviour controlled by habits. This has supported the notion of addiction as a “drug habit”, and has led to considerable advances in understanding the neurobiological basis of such behaviour. While drug-taking involves habitual behaviours, the initial procurement of drugs may require considerable flexibility in seeking behaviour which, by definition, is not habitual. The proposed studies model this pattern of flexible reward-seeking and rigid reward-taking, requiring mice to solve a new puzzle every day to gain access to reward. Across weeks of observation, we will use photometry to watch real-time neuronal activity in the brain while rats seek and take reward. These biopsychological experiments provide the foundation for work in our new laboratory, which we hope will impact how people view and treat addictions.
|Role||Start date||End date||Funding source|
|Co-investigator||01 Oct 2018||30 Sep 2021||King's College London (KCLU)|
£10k for consumables from King's College London, collaboration with Dr Ellie Dommett. For Morgane Colom's studentship.
|Role||Start date||End date||Funding source|
|Lead||01 Apr 2016||31 Mar 2019||NC3Rs (National Centre for the Replacement Refinement and Reduction of Animals in Research)|
The focus of this project is to develop and validate a series of non-invasive behavioural assessments for laboratory rodents that will enable routine evaluation of motivation and affective state. These assays will be designed with a lower severity band (refinement) and require fewer animals (reduction) than current methods.
Using touchscreen-delivered cognitive assessments to address the principles of the 3Rs in behavioural sciences (2021-07)
Lopez-Cruz, Laura; Bussey, Timothy J.; Saksida, Lisa M. and Heath, Christopher
Lab Animal, 50 (pp. 174-184)
Coexistence of perseveration and apathy in the TDP-43Q331K knock-in mouse model of ALS–FTD (2020)
Kim, Eosu; White, Matthew A.; Phillips, Benjamin U.; Lopez-Cruz, Laura; Kim, Hyunjeong; Heath, Christopher J.; Lee, Jong Eun; Saksida, Lisa M.; Sreedharan, Jemeen and Bussey, Timothy J.
Translational Psychiatry, 10, Article 377(1)
A touchscreen motivation assessment evaluated in Huntington’s disease patients and R6/1 model mice (2019-08-09)
Heath, Christopher; O'Callaghan, Claire; Mason, Sarah L; Phillips, Benjamin U; Saksida, Lisa M; Robbins, Trevor W; Barker, Roger A; Bussey, Timothy J and Sahakian, Barbara J
Frontiers in Neurology, 10, Article 858
Blockade of muscarinic acetylcholine receptors facilitates motivated behaviour and rescues a model of antipsychotic-induced amotivation (2019-05)
Hailwood, Jonathan M.; Heath, Christopher J.; Phillips, Benjamin U.; Robbins, Trevor W.; Saksida, Lisa M. and Bussey, Timothy J.
Neuropsychopharmacology, 44 (pp. 1068-1075)
Assessment of mGluR5 KO mice under conditions of low stress using a rodent touchscreen apparatus reveals impaired behavioural flexibility driven by perseverative responses (2019-04-11)
Lim, Jisoo; Kim, Eosu; Noh, Hyun Jong; Kang, Shinwon; Phillips, Benjamin U.; Kim, Dong Goo; Bussey, Timothy J.; Saksida, Lisa M.; Heath, Christopher J. and Kim, Chul Hoon
Molecular Brain, 12, Article 37
Pre- and postnatal high fat feeding differentially affects the structure and integrity of the neurovascular unit of 16-month old male and female mice (2019)
Contu, Laura; Nizari, Shereen; Heath, Christopher J. and Hawkes, Cheryl A.
Frontiers in Neuroscience, 13, Article 1045
Continuous performance test impairment in a 22q11.2 microdeletion mouse model: improvement by amphetamine (2018-11-14)
Nilsson, Simon R.O.; Heath, Christopher J.; Takillah, Samir; Didienne, Steve; Fejgin, Kim; Nielsen, Vibeke; Nielsen, Jacob; Saksida, Lisa M.; Mariani, Jean; Faure, Philippe; Didriksen, Michael; Robbins, Trevor W.; Bussey, Timothy J. and Mar, Adam C.
Translational Psychiatry, 8, Article 247
Validation and optimisation of a touchscreen progressive ratio test of motivation in male rats (2018-09-30)
Hailwood, Jonathan M.; Heath, Christopher J.; Robbins, Trevor W.; Saksida, Lisa M. and Bussey, Timothy J.
Psychopharmacology, 235(9) (pp. 2739-2753)
Selective effects of 5-HT2C receptor modulation on performance of a novel valence-probe visual discrimination task and probabilistic reversal learning in mice (2018-07)
Phillips, Benjamin U.; Dewan, Sigma; Nilsson, Simon R. O.; Robbins, Trevor W.; Heath, Christopher J.; Saksida, Lisa M.; Bussey, Timothy J. and Alsiö, Johan
Psychopharmacology, 235(7) (pp. 2101-2111)
Longitudinal evaluation of Tau-P301L transgenic mice reveals no cognitive impairments at 17 months of age (2018-01-29)
Kent, Brianne A.; Heath, Christopher J.; Kim, Chi Hun; Ahrens, Rosemary; Fraser, Paul E.; St George-Hyslop, Peter; Bussey, Timothy J. and Saksida, Lisa M.
Brain and Behavior, 8, Article e00896(1)
Translational approaches to evaluating motivation in laboratory rodents: conventional and touchscreen-based procedures (2018)
Phillips, Benjamin U.; Lopez-Cruz, Laura; Hailwood, Jonathan; Heath, Christopher J.; Saksida, Lisa M. and Bussey, Timothy J.
Current Opinion in Behavioral Sciences, 22 (pp. 21-27)
Optimisation of cognitive performance in rodent operant (touchscreen) testing: Evaluation and effects of reinforcer strength (2017-09)
Phillips, Benjamin U.; Heath, Christopher J.; Ossowska, Zofia; Bussey, Timothy J. and Saksida, Lisa M.
Learning and Behavior, 45(3) (pp. 252-262)
Accumbal cholinergic interneurons differentially influence motivation related to satiety signaling (2017-04-30)
Aitta-aho, Teemu; Phillips, Benjamin U.; Pappa, Elpiniki; Hay, Y. Audrey; Harnischfeger, Fiona; Heath, Christopher J.; Saksida, Lisa M.; Bussey, Timothy J. and Apergis-Schoute, John
eNeuro, 4, Article e0328-16(2)
Optimizing reproducibility of operant testing through reinforcer standardization: identification of key nutritional constituents determining reward strength in touchscreens (2017)
Kim, Eun Woo; Phillips, Benjamin U.; Heath, Christopher J.; Cho, So Yeon; Kim, Hyunjeong; Sreedharan, Jemeen; Song, Ho-Taek; Lee, Jong Eun; Bussey, Timothy J.; Kim, Chul Hoon; Kim, Eosu and Saksida, Lisa M.
Molecular Brain, 10, Article 31
A mouse model of the 15q13.3 microdeletion syndrome shows prefrontal neurophysiological dysfunctions and attentional impairment. (2016-06-30)
Nilsson, Simon R. O.; Celada, Pau; Fejgin, Kim; Thelin, Jonas; Nielsen, Jacob; Santana, Noemí; Heath, Christopher J.; Larsen, Peter H.; Nielsen, Vibeke; Kent, Brianne A.; Saksida, Lisa M.; Stensbøl, Tine B.; Robbins, Trevor W.; Bastlund, Jesper F.; Bussey, Timothy J.; Artigas, Francesc and Didriksen, Michael
An epigenetic mechanism mediates developmental nicotine effects on neuronal structure and behavior (2016-05-30)
Jung, Yonwoo; Hsieh, Lawrence S.; Lee, Angela M.; Zhou, Zhifeng; Coman, Daniel; Heath, Christopher J.; Hyder, Fahmeed; Mineur, Yann S; Yuan, Qiaoping; Goldman, David; Bordey, Angelique and Picciotto, Marina R
Nature Neuroscience, 19(7) (pp. 905-914)
Motivational assessment of mice using the touchscreen operant testing system: effects of dopaminergic drugs (2015-11-01)
Heath, Christopher J.; Bussey, Timothy J. and Saksida, Lisa M.
Psychopharmacology, 232(21) (pp. 4043-4057)
Facilitation of spatial working memory performance following intra-prefrontal cortical administration of the adrenergic alpha1 agonist phenylephrine. (2015-11)
Hvoslef-Eide, Martha; Oomen, C. A.; Fisher, B. M.; Heath, C. J.; Robbins, T. W.; Saksida, L. M. and Bussey, T. J.
Psychopharmacology, 232(21) (pp. 4005-4016)
Trial-unique, delayed nonmatching-to-location (TUNL) touchscreen testing for mice: sensitivity to dorsal hippocampal dysfunction. (2015-11)
Kim, Chi Hun; Romberg, Carola; Hvoslef-Eide, Martha; Oomen, Charlotte A.; Mar, Adam C.; Heath, Christopher J.; Berthiaume, Andrée-Anne; Bussey, Timothy J. and Saksida, Lisa M.
Psychopharmacology, 232(21) (pp. 3935-3945)
The role of the dorsal hippocampus in two versions of the touchscreen automated paired associates learning (PAL) task for mice. (2015-11)
Kim, Chi Hun; Heath, Christopher J.; Kent, Brianne A.; Bussey, Timothy J. and Saksida, Lisa M.
Psychopharmacology, 232(21) (pp. 3899-3910)
The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia (2015-07-24)
Hvoslef-Eide, M.; Mar, A. C.; Nilsson, S. R. O.; Alsiö, J.; Heath, C. J.; Saksida, L. M.; Robbins, T. W. and Bussey, T. J.
The touchscreen operant platform for testing working memory and pattern separation in rats and mice. (2013-10)
Oomen, Charlotte A.; Hvoslef-Eide, Martha; Heath, Christopher J.; Mar, Adam C.; Horner, Alexa E.; Bussey, Timothy J. and Saksida, Lisa M.
Nature Protocols, 8(10) (pp. 2006-2021)
The touchscreen operant platform for testing learning and memory in rats and mice. (2013-10)
Horner, Alexa E.; Heath, Christopher J.; Hvoslef-Eide, Martha; Kent, Brianne A.; Kim, Chi Hun; Nilsson, Simon R. O.; Alsiö, Johan; Oomen, Charlotte A.; Holmes, Andrew; Saksida, Lisa M. and Bussey, Timothy J.
Nature Protocols, 8(10) (pp. 1961-84)
False recognition in a mouse model of Alzheimer's disease: rescue with sensory restriction and memantine. (2012-07)
Romberg, Carola; McTighe, Stephanie M.; Heath, Christopher J.; Whitcomb, Daniel J.; Cho, Kwangwook; Bussey, Timothy J. and Saksida, Lisa M.
Brain : a journal of neurology, 135(7) (pp. 2103-2114)
Impaired auditory discrimination learning following perinatal nicotine exposure or β2 nicotinic acetylcholine receptor subunit deletion (2012-05-16)
Horst, Nicole K.; Heath, Christopher J.; Neugebauer, Nichole M.; Kimchi, Eyal Y.; Laubach, Mark and Picciotto, Marina R.
Behavioural Brain Research, 231(1) (pp. 170-180)
Oral nicotine consumption does not affect maternal care or early development in mice but results in modest hyperactivity in adolescence. (2010-12-02)
Heath, Christopher J.; Horst, Nicole K. and Picciotto, Marina R.
Physiology & behavior, 101(5) (pp. 764-769)
Cortico-Thalamic Connectivity is Vulnerable to Nicotine Exposure During Early Postnatal Development through α4/β2/α5 Nicotinic Acetylcholine Receptors (2010-11)
Heath, Christopher J.; King, Sarah L.; Gotti, Cecilia; Marks, Michael J. and Picciotto, Marina R.
Neuropsychopharmacology, 35(12) (pp. 2324-2338)
Allelic variation of calsyntenin 2 (CLSTN2) modulates the impact of developmental tobacco smoke exposure on mnemonic processing in adolescents. (2009-04-15)
Jacobsen, Leslie K.; Picciotto, Marina R.; Heath, Christopher J.; Mencl, W. Einar and Gelernter, Joel
Biological Psychiatry, 65(8) (pp. 671-679)
Nicotine-induced plasticity during development: modulation of the cholinergic system and long-term consequences for circuits involved in attention and sensory processing. (2009)
Heath, Christopher J. and Picciotto, Marina R.
Neuropharmacology, 56(Sup 1) (pp. 254-262)
Prenatal and Adolescent Exposure to Tobacco Smoke Modulates the Development of White Matter Microstructure (2007-12-05)
Jacobsen, Leslie K.; Picciotto, Marina R.; Heath, Christopher; Frost, Stephen J.; Tsou, Kristen A.; Dwan, Rita A.; Jackowski, Marcel P.; Constable, Robert T. and Mencl, W. Einar
The Journal of Neuroscience, 27(49) (pp. 13491-13498)
Nicotine-induced phosphorylation of ERK in mouse primary cortical neurons: evidence for involvement of glutamatergic signaling and CaMKII. (2007-10)
Steiner, Rebecca C.; Heath, Christopher J. and Picciotto, Marina R.
Journal of Neurochemistry, 103(2) (pp. 666-78)
Measuring Motivation and Reward-Related Decision Making in the Rodent Operant Touchscreen System. (2016-01-04)
Heath, Christopher J.; Phillips, Benjamin U.; Bussey, Timothy J. and Saksida, Lisa M.
In: Gerfen, Charles R.; Holmes, Andrew; Sibley, David; Skolnick, Phil and Wray, Susan eds. Current Protocols in Neuroscience (pp. 8.34.1-8.34.20)
ISBN : 9780471142300 | Publisher : John Wiley & Sons | Published : Chichester