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Dr Christopher Heath

Senior Lecturer In Health Sciences

School of Life, Health & Chemical Sciences

christopher.heath@open.ac.uk

Biography

Research interests

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:

  1. Development and validation of a new battery of touchscreen-based assessments for the routine evaluation of motivation and affective state
  2. Touchscreen-based assessment for evaluating the impact of circadian rhythm disruption on cognitive performance
  3. Assessment of the persistent consequences of poor maternal diet and maternal smoking on offspring cognition
  4. Investigating the neurobiological correlates of apathy in Huntington’s disease

 

OU Collaborators:

Laura Lopez-Cruz, School of Life, Health and Chemical Sciences

 

International Collaborators:

Tim Bussey and Lisa Saksida, University of Western Ontario, Canada

Eosu Kim, Yonsei University, Korea

Projects

Personalised epigenetic therapies for sarcoma

This will be a one-day symposium aimed at sarcoma (clinical specialists and researchers). Attendance will be in person (encouraged) or on-line (via Teams). We will aim to obtain CPD accreditation, as per other symposia organised by our group.

A translational approach to study individual differences in cognitive affective bias: neural underpinnings of vulnerability to depression

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.

Postgraduate Research and Professional Development - Morgane Colom

£10k for consumables from King's College London, collaboration with Dr Ellie Dommett. For Morgane Colom's studentship.

Neuronal encoding of flexible reward-seeking and rigid reward-taking

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.

TRANSFER IN: Development and validation of a rodent touchscreen battery for assessing motivation and affective state

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.

Publications

Book Chapter

Motivation – Behavioral Approaches and Translational Potential (2022)

Measuring Motivation and Reward-Related Decision Making in the Rodent Operant Touchscreen System. (2016)

Journal Article

Conditioning‐ and reward‐related dendritic and presynaptic plasticity of nucleus accumbens neurons in male and female sign‐tracker rats (2024)

Developmental origin of oligodendrocytes determines their function in the adult brain (2024)

Refining the study of decision-making in animals: differential effects of d-amphetamine and haloperidol in a novel touchscreen-automated Rearing-Effort Discounting (RED) task and the Fixed-Ratio Effort Discounting (FRED) task (2024)

Reconsidering repurposing: long-term metformin treatment impairs cognition in Alzheimer’s model mice (2024)

Appetitive motivation and associated neurobiology change differentially across the life course of mouse offspring exposed to peri- and postnatal high fat feeding (2022)

The effect of the COVID-19 pandemic on disgust sensitivity in a sample of UK adults (2022)

α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression (2022)

Using touchscreen-delivered cognitive assessments to address the principles of the 3Rs in behavioural sciences (2021)

Coexistence of perseveration and apathy in the TDP-43Q331K knock-in mouse model of ALS–FTD (2020)

A touchscreen motivation assessment evaluated in Huntington’s disease patients and R6/1 model mice (2019)

Blockade of muscarinic acetylcholine receptors facilitates motivated behaviour and rescues a model of antipsychotic-induced amotivation (2019)

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)

Continuous performance test impairment in a 22q11.2 microdeletion mouse model: improvement by amphetamine (2018)

Validation and optimisation of a touchscreen progressive ratio test of motivation in male rats (2018)

Selective effects of 5-HT2C receptor modulation on performance of a novel valence-probe visual discrimination task and probabilistic reversal learning in mice (2018)

Longitudinal evaluation of Tau-P301L transgenic mice reveals no cognitive impairments at 17 months of age (2018)

Translational approaches to evaluating motivation in laboratory rodents: conventional and touchscreen-based procedures (2018)

Optimisation of cognitive performance in rodent operant (touchscreen) testing: Evaluation and effects of reinforcer strength (2017)

Optimizing reproducibility of operant testing through reinforcer standardization: identification of key nutritional constituents determining reward strength in touchscreens (2017)

Accumbal cholinergic interneurons differentially influence motivation related to satiety signaling (2017)

A mouse model of the 15q13.3 microdeletion syndrome shows prefrontal neurophysiological dysfunctions and attentional impairment. (2016)

An epigenetic mechanism mediates developmental nicotine effects on neuronal structure and behavior (2016)

Facilitation of spatial working memory performance following intra-prefrontal cortical administration of the adrenergic alpha1 agonist phenylephrine. (2015)

Trial-unique, delayed nonmatching-to-location (TUNL) touchscreen testing for mice: sensitivity to dorsal hippocampal dysfunction. (2015)

Motivational assessment of mice using the touchscreen operant testing system: effects of dopaminergic drugs (2015)

The role of the dorsal hippocampus in two versions of the touchscreen automated paired associates learning (PAL) task for mice. (2015)

The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia (2015)

The touchscreen operant platform for testing learning and memory in rats and mice. (2013)

The touchscreen operant platform for testing working memory and pattern separation in rats and mice. (2013)

False recognition in a mouse model of Alzheimer's disease: rescue with sensory restriction and memantine. (2012)

Impaired auditory discrimination learning following perinatal nicotine exposure or β2 nicotinic acetylcholine receptor subunit deletion (2012)

Oral nicotine consumption does not affect maternal care or early development in mice but results in modest hyperactivity in adolescence. (2010)

Cortico-Thalamic Connectivity is Vulnerable to Nicotine Exposure During Early Postnatal Development through α4/β2/α5 Nicotinic Acetylcholine Receptors (2010)

Allelic variation of calsyntenin 2 (CLSTN2) modulates the impact of developmental tobacco smoke exposure on mnemonic processing in adolescents. (2009)

Nicotine-induced plasticity during development: modulation of the cholinergic system and long-term consequences for circuits involved in attention and sensory processing. (2009)

Prenatal and Adolescent Exposure to Tobacco Smoke Modulates the Development of White Matter Microstructure (2007)

Nicotine-induced phosphorylation of ERK in mouse primary cortical neurons: evidence for involvement of glutamatergic signaling and CaMKII. (2007)