Host institution: University of Bristol, UK

ESR7 Functional anatomical mapping of cerebellar connections with limbic structures and fear extinction

Behavioural studies in rats have shown there is a spectrum of behavioural responses during retrieval and extinction of a fear memory. These differences may parallel individual emotional responses in humans and provide a novel insight into susceptibility to certain diseases. For example the inability to extinguish a fear memory in individuals might lead to anxiety disorders and chronic pain. This project will use cerebellar deep brain stimulation (cDBS) and FosGFP to functionally map pathways that link the cerebellum with limbic structures in rats. A key unknown is the underlying neural networks that cerebellar stimulation activates to produce effects on higher order, including emotional circuits.

Experiments will include behavioural studies using a fear conditioning paradigm in rats to identify animals that show high versus low freezing activity during fear extinction. Once animals have been separated into these groups, pathways will be mapped using FosGFP activation.

The effects of cerebellar stimulation on different phases of fear conditioning will be tested to determine whether manipulation of different pathways can affect freezing levels during fear extinction. For example, together with appropriate controls, the effects of cDBS will be applied: (i) during and (ii) immediately after the acquisition phase of conditioned fear to study its effect on subsequent conditioned fear response retrieval and rates of extinction.

These experiments will define the neural network activity at the cellular level of cerebellar stimulation, including interactions with limbic structures.

Planned secondments: Essen, month 13-14, purpose: to compare cerebellar stimulation experiments in rodents and human; Cerevance, month 25, purpose: training in Biotech industry.