Principal Supervisor: Dr James McCutcheon, Department of Neuroscience, Psychology and Behaviour
Co-supervisor: Dr John Apergis-Schoute
PhD project title: Integration of sensory input with motivational state
University of Registration: University of Leicester
We live in a staggeringly complex world in which our brain is constantly required to process an abundance of sensory inputs. How these different inputs are processed and prioritised by the brain is a fascinating subject but one that is still poorly understood. Importantly, decisions about how to respond to a particular sensory input are strongly influenced by motivational states such as hunger or fear. For example, if an animal is hungry it is unlikely to interpret a neutral noise as a threat whereas if it is fearful the same noise may be perceived as threatening. The neural circuits that sit at the intersection of sensory input and behavioural output have a crucial role to play in this process by integrating inputs with motivational state and allowing animals to make appropriate behavioural decisions. Understanding how these circuits work is important as several psychiatric disorders (e.g. schizophrenia, post-traumatic stress disorder) involve dysfunctional processing of sensory input. Research into these fundamental processes will therefore shed light on these devastating conditions. Thus, the aim of this project is to understand how sensory input is integrated with motivational state and to determine the neural circuits subserve this.
In our lab we approach this problem by considering how different sensory inputs affect feeding behaviour under different motivational states . For example, when hungry it may be less likely that we will be distracted by non-food related sensory stimuli. On the other hand, if anxious or fearful, mild, neutral sensory events might evoke stronger responses and inhibit feeding. We use a distraction task  in rats that allows us to record ongoing neural activity and neurotransmitter release while freely-moving rats explore an environment, sample different foods, and are exposed to sensory stimuli. In these studies, rats have access to bottles fitted with lickometers that monitor every lick. At pseudorandom times while rats are licking, sensory stimuli (lights, tones) are presented and we check to see whether licking was inhibited. We have shown that, in a model of schizophrenia, rats are more distracted by the distracting stimuli than control rats.
To probe the neural circuits involved in this process we will use a cutting-edge technique called fibre photometry that allows neural activity to be recorded from deep brain structures . A calcium indicator is expressed in a subset of neurons meaning that the neurons’ fluorescence increases as they become more active. Using this method, we have seen robust responses to distracting stimuli in dopamine neurons and hypothalamic neurons.
Aim 1 will evaluate how distraction is modulated by different motivational states using behavioural paradigms, e.g. hunger vs. satiety, bright vs. dim lights, saccharin (no calories) vs. sugar (calories).
Aim 2 will determine how subsets of neurons in hypothalamus are activated during the distraction task using in vivo fibre photometry.
Aim 3 will analyse the projections and synaptic connectivity of identified hypothalamic neurons using anatomical and in vitro electrophysiological/optogenetic methods.
This project will combine the different skill-sets of Dr. McCutcheon (PI) and Dr. Apergis-Schoute (Co-I) to yield interdisciplinary findings on the role of hypothalamic neurons in integrating sensory inputs and motivational state. Dr. McCutcheon has extensive experience conducting in vivo physiology experiments and is an expert on feeding behaviour and motivation. Dr Apergis-Schoute has several publications using optogenetics to perform in vitro circuit mapping and has recorded extensively in hypothalamus.
- Cone JJ et al (2016) PNAS, doi: 10.1073/pnas.1519643113
- O’Connor EC et al (2015) Neuron, doi: 10.1016/j.neuron.2015.09.038
- Zalocusky KA et al (2016) Nature, doi: 10.1038/nature17400
BBSRC Strategic Research Priority: Molecules, cells and systems
Techniques that will be undertaken during the project:
- In vivo fibre photometry
- Behavioural studies of feeding and motivation
- Advanced surgical skills
- Optogenetic circuit interrogation (in vivo and in vitro)
- Anatomical tracing of neural circuits