Host institution: University Hospital Würzburg, Germany

ESR3 – Signal integration within reciprocal cerebellar-brainstem circuits during aversive emotional states

This project will use the latest deep-brain calcium imaging technology (miniscope, Inscopix), to monitor activity of identified cell types within the cerebellum and brainstem of mice, with a focus on defensive states. This project will address the hypothesis that cerebellar-PAG circuits form a crucial network element that modulates aversive emotions via somatosensory integration of behavioural and autonomic responses. To characterize specific functional pathways, e.g. ascending vs. descending cerebellar-PAG connections, we will use double-conditional, intersectional viral strategies to target cell-types with distinct projection targets (see ESR6). Freely moving mice will be subjected to behavioural assays such as the open field test and elevated plus maze to evoke different levels of fear and/or anxiety and adaptive behavioural coping strategies. Mice will also be equipped with subcutaneously implanted electrodes for recording of muscle activity and electrocardiogram. Furthermore, we will employ the recently developed conditioned flight paradigm to investigate cue- and context- dependent switching between passive and active threat coping. This will allow monitoring of potential “online prediction errors” and their putative relation with moment-to-moment integrated defense states. The results will be compared to the electrophysiological findings obtained in ESRs1, 2 and 5 and directly compared to calcium imaging results in ESR4. Collaboration with Pavia in analysis of calcium imaging data to incorporate into a computational model.

The resulting comprehensive dataset will allow to identify specific neuronal correlates within cerebellar-PAG circuits for distinct integrated defense states. Furthermore, temporal decoding of calcium activity will reveal the neural population dynamics of “online prediction error” generation.

Planned secondments: INSCOPIX, month 7, purpose: training in miniscope technology; Pavia, month 16 – 18, purpose: collaboration in imaging to investigate neural population activity within the cerebellar cortex.