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Abstract

To survive, animals have to finely regulate their threat assessment and escape behavior. In mice, the brainstem dorsal periaqueductal grey (dPAG) generates innate defensive behaviors towards a multitude of threats, like predators, prey and aggressive conspecifics. dPAG acts as a switchboard between forebrain areas like the anterior cingulate cortex (ACC) and the brainstem. Glutamatergic neurons in the ACC project to dPAG and have an inhibitory effect on the structure, promoting approach. In dPAG, separate neuron ensembles correlate with risk assessment or with escape. However, the differential connectivity and gene expression of these two classes remains unknown. In this thesis, I aimed at better understand the anatomy and function of the dPAG microcircuits controlling assessment and escape behavior. To do so, I performed single neuron calcium imaging recordings with a miniaturized fluorescent microscope in freely moving mice in glutamatergic and GABAergic neurons in dPAG, showing that both cell types correlated with assessment and escape in a social, predatorial and prey threat exposure test. Furthermore, I used volume electron microscopy combined with multiplexed labeling of pre- and postsynapses, showing that ACC axons establish synapses onto Vglut2+ and non-glutamatergic, non-GABAergic neurons in dPAG, pointing to the role of a neuromodulator neuron class mediating dPAG inhibition. Further experiments will analyze the expression profile of dPAG neurons, with a focus on ACC synaptic partners, using spatially resolved transcriptomics, and will explore the functional role of dPAG candidate neuromodulatory neurons in defensive behaviors, such as enkephalin expressing neurons. In conclusion, my PhD work characterized the connectivity and function of a brainstem neural circuit that modulates innate defensive behaviors towards aggressive conspecifics, predators and prey in mice.