Clocks, Reward, and Disappointment
Lead Research Organisation:
University of Manchester
Department Name: School of Medical Sciences
Abstract
Clocks, Reward, and Disappointment
All cells in our brain and body contain a molecular clock that drives daily rhythms in our physiology and behaviour including patterns of sleeping, eating, drinking, and information processing. Intriguingly, our moods and desires also fluctuate over the day and this variation emerges through interactions between specialised daily clock and reward circuits in our brain. How these circuits share information is unclear, but current evidence indicates that the habenula of the brain's epithalamus is at the interface of these two systems. The habenula acts as a conduit between the forebrain and the midbrain, and is implicated as a key component of a circuit mediating disappointment. Habenula neurons are sensitive to nicotine and process both acute rewarding as well as negative withdrawal effects of this active component of tobacco. Importantly, neurons in the habenula receive visual input and also vary their activity across the day and night, suggesting that this structure has intrinsic timekeeping capabilities. However, it is unknown how daily rhythms in molecular and cellular activity in the habenula influence animal behaviour and responses to rewarding stimuli such as nicotine. In this project, state of the art in vivo and in vitro recording and imaging approaches will be used, in combination with novel and selective nicotinic receptor modulators, intersectional genetics tools and appropriate behavioural tests. Together, these will establish how the habenula integrates light, clock and reward signals to influence brain and behavioural responses. Ultimately, these studies may lead to improved therapeutic strategies for the cessation of nicotine consumption.
This project will provide novel interdisciplinary training in bioimaging, electrophysiological, and behavioural techniques in both in vivo and in vitro experimental settings. These will involve training in analysis of complex neural data sets. Specifically, the student will be trained to perform:
i) Large scale multi-electrode recordings in vivo and in vitro, combined with sophisticated off-line analyses using both commercial and bespoke software programmes (e.g., Matlab, NeuroExplorer, OfflineSorter).
ii) Intraneural injections and opto-/chemo-genetic manipulation and circuit mapping of defined neuronal populations in vivo and in vitro.
ii) Behavioural assays for acute and rewarding drug effects with simultaneous neuronal monitoring.
All cells in our brain and body contain a molecular clock that drives daily rhythms in our physiology and behaviour including patterns of sleeping, eating, drinking, and information processing. Intriguingly, our moods and desires also fluctuate over the day and this variation emerges through interactions between specialised daily clock and reward circuits in our brain. How these circuits share information is unclear, but current evidence indicates that the habenula of the brain's epithalamus is at the interface of these two systems. The habenula acts as a conduit between the forebrain and the midbrain, and is implicated as a key component of a circuit mediating disappointment. Habenula neurons are sensitive to nicotine and process both acute rewarding as well as negative withdrawal effects of this active component of tobacco. Importantly, neurons in the habenula receive visual input and also vary their activity across the day and night, suggesting that this structure has intrinsic timekeeping capabilities. However, it is unknown how daily rhythms in molecular and cellular activity in the habenula influence animal behaviour and responses to rewarding stimuli such as nicotine. In this project, state of the art in vivo and in vitro recording and imaging approaches will be used, in combination with novel and selective nicotinic receptor modulators, intersectional genetics tools and appropriate behavioural tests. Together, these will establish how the habenula integrates light, clock and reward signals to influence brain and behavioural responses. Ultimately, these studies may lead to improved therapeutic strategies for the cessation of nicotine consumption.
This project will provide novel interdisciplinary training in bioimaging, electrophysiological, and behavioural techniques in both in vivo and in vitro experimental settings. These will involve training in analysis of complex neural data sets. Specifically, the student will be trained to perform:
i) Large scale multi-electrode recordings in vivo and in vitro, combined with sophisticated off-line analyses using both commercial and bespoke software programmes (e.g., Matlab, NeuroExplorer, OfflineSorter).
ii) Intraneural injections and opto-/chemo-genetic manipulation and circuit mapping of defined neuronal populations in vivo and in vitro.
ii) Behavioural assays for acute and rewarding drug effects with simultaneous neuronal monitoring.