ESR5 – Cerebellar contributions to the control of integrated affective behaviours in high versus low anxiety rats
This project will explore the possibility that cerebellar modules differ in their control of affective behaviour, depending on anxiety phenotype. The details of the project will be tailored to the student’s interest but will include comparison in high versus low anxiety phenotypes of rat and manipulation of neural circuits using the latest viral transfection methods (e.g. cre-dependent DREADDs). The effect of circuit manipulations in the cerebellum will be studied during behavioural paradigms that elicit negative versus positive affective responses (e.g. behaviours that elicit fear/anxiety such as fear conditioning, elevated plus maze, open field and lever press for reward).
There will be a focus on integrated behavioural outputs including somatomotor, autonomic and ultrasonic vocalisations. The experiments may include the use of state-of-the-art multi brain site electrophysiological recording and/or calcium imaging, together with ECG to investigate neural encoding in different anxiety phenotypes (including the possibility of gender differences); and the effect of the manipulations on neural circuit and cardiovascular activity.
These experiments will provide new insights into cerebellar contributions to integrated behavioural responses elicited by affective state.
The results will be compared to the electrophysiological and calcium imaging findings obtained in ESRs 1-4 and related clinical research (ESR10). Collaboration with Wurzburg will provide guidance on the use of viral techniques and calcium imaging (e.g. Purkinje cell specific promoters).
Planned secondments: Blackrock microsystems, month 11, purpose: training in latest multi-channel recording to investigate neural circuit dynamics; Wurzburg, months 13 – 15, purpose: to learn how to make state of the art viruses targeting cerebellar Purkinje cells.