ALL-OPTICAL CONNECTOME IMAGING AND MOLECULAR PROFILING OF COLLATERAL VENTROMEDIAL HYPOTHALAMIC NEURONS

Defensive behaviors play a pivotal role for survival. Depending on sensory input, behavioral output results in escape, freezing or attack. The ventromedial hypothalamic nucleus (VMH) is crucial for selecting the best escape strategy. The VMH has been shown to project to downstream structures, where the signaling to the anterior hypothalamic nucleus (AHN) was linked to an escape, whereas the signalling to the periaqueductal gray (PAG) to an immobility behavior. While the dorsal/central VMH was shown to have projections to both regions, the molecular identity and synaptic signal integration of neurons projecting to both regions remain to be investigated.
In this work we used viral labeling strategies combined with all-optical voltage imaging and characterized the post-synaptic connectome of VMH collateral cells. Using all-optical imaging we could reconstruct the postsynaptic response types of AHN and of PAG and analyze their spatial localization as well. In addition, we investigated sequencing based molecular identity of the VMH collateral neurons and their population-level diversity.
This work provides further insights to the connectome underlying defensive behaviors, which is crucial to find underlying malfunctions in human mental disorders like post-traumatic stress disorder.