Connectional architecture of a mouse hypothalamic circuit node controlling social behavior

Type 1 Estrogen receptor-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl Esr1 ) play a causal role in the control of social behaviors including aggression. Here we use six different viral-genetic tracing methods to map the connectional architecture of VMHvl Esr1 neurons. These data reveal a high level of input convergence and output divergence (9fan-in/fan-out9) from and to over 30 distinct brain regions, with a high degree (~90%) of recurrence. Unlike GABAergic populations in other hypothalamic nuclei controlling feeding and parenting behavior, VMHvl Esr1 glutamatergic neurons collateralize to multiple targets. However, we identify two anatomically distinct subpopulations with anterior vs. posterior biases in their collateralization patterns. Surprisingly, these two subpopulations receive indistinguishable inputs. These studies suggest an overall system architecture in which an anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. This architecture differs from the 9brain-inspired9 feed-forward circuits used in certain types of artificial intelligence networks.