@article {69729,
	title = {Collateral connectomes of Esr1-positive hypothalamic neurons modulate defensive behavior plasticity},
	journal = {bioRxiv},
	year = {2025},
	month = {01/2025},
	abstract = {<p>The ventromedial hypothalamus (VMH) projects to the periaqueductal gray (PAG) and anterior hypothalamic nucleus (AHN), mediating freezing and escape behaviors, respectively. We investigated VMH collateral (VMH-coll) neurons, which innervate both PAG and AHN, to elucidate their role in postsynaptic processing and defensive behavior plasticity. Using all-optical voltage imaging of 22,151 postsynaptic neurons ex vivo, we found that VMH-coll neurons engage inhibitory mechanisms at both synaptic ends and can induce synaptic circuit plasticity. In vivo optogenetic activation of the VMH-coll somas induced escape behaviors. We identified an Esr1-expressing VMH-coll subpopulation with postsynaptic connectome resembling that of wild-type collaterals on the PAG side. Activation of Esr1+VMH-coll neurons evoked freezing and unexpected flattening behavior, previously not linked to the VMH. Neuropeptides such as PACAP and dynorphin modulated both Esr1+VMH-coll connectomes. In vivo κ-opioid receptor antagonism impaired Esr1+VMH-coll-mediated defensive behaviors. These findings unveiled the central role of VMH-coll pathways in innate defensive behavior plasticity.</p>
},
	doi = {10.1101/2025.01.10.632334},
	url = {https://www.biorxiv.org/content/early/2025/01/11/2025.01.10.632334},
	author = {Csillag, Veronika and Forastieri, Chiara and Sz{\"u}cs, Gr{\'e}ta Martina and Vidal, In{\'e}s Talaya and Bizzozzero, Marianne Hiriart and Lavis, Luke D. and Calvigioni, Daniela and Fuzik, J{\'a}nos}
}
