Host institution: École Normale Supérieure, Paris, France

ESR2 – Cerebello-limbic system neuronal dynamics during fear conditioning and extinction

The goal of this project is to understand the mechanisms and the operations performed in the cerebellum and cerebello-thalamo-prefrontal pathway during fear learning in mice. We have preliminary data showing anatomical and physiological connections between cerebellum, and prefrontal cortex via medio-dorsal thalamus (MD), which is known to be important for fear extinction. We will now evaluate the correlated patterns of neuronal activity with fear learning using electrophysiological recording in vivo, during different phases of fear conditioning in the limbic system (MD thalamus, prefrontal cortex) in freely moving animals coupled with optogenetic stimulation (theta-burst) to test the cerebello-limbic functional link and to modulate this link in order to modify emotional behaviour.

Anxiety will be measured in open field experiments, in dark/light compartment boxes and elevated cross labyrinth, before and after optogenetic cerebellar modulation. A startle test will also be performed using our accelerometer to accurately quantify the startle responses. The feasibility of this project is very high because all techniques and analysis are already implemented in the respective labs. Collaboration with Essen (ESR13) will compare the effects of cerebellar theta burst stimulation in mice with similar non -invasive stimulation in human subjects.

Overall, these experiments will provide new insights into the neurophysiological processes (cell discharge, oscillations, synchrony across limbic structures) controlled by the cerebellum during fear learning and extinction and will determine the effect of cerebellar manipulations on these processes.

Planned secondments: Cerevance, month 13, purpose: training in Biotech industry; Essen, month 24, purpose: to compare animal work with related stimulation in clinical stimulation research (ESR10); Wurzburg: month 36, purpose: integrate electrical and calcium imaging data.