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bioRxiv · 10.1101/445312

Connectional architecture of a mouse hypothalamic circuit node controlling social behavior

Lo, L.·Kim, D.-W.·Yao, S.·Cetin, A.·Harris, J.·Zeng, H.·Anderson, D. J.·Weissbourd, B.
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Abstract

Type 1 Estrogen receptor-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvlEsr1) 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 VMHvlEsr1 neurons. These data reveal a high level of input convergence and output divergence (\"fan-in/fan-out\") 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, VMHvlEsr1 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 \"brain-inspired\" feed-forward circuits used in certain types of artificial intelligence networks.\n\nSIGNIFICANCEHow the cellular heterogeneity of brain nuclei maps onto circuit connectivity, the relationship of this anatomical mapping to behavioral function, and whether there are general principles underlying this relationship, remains poorly understood. Here we systematically map the connectivity of estrogen receptor-1-expressing neurons in the ventromedial hypothalamus (VMHvlEsr1), which control aggression and other social behaviors. We find that a relatively sparse, anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. Further, the VMHvl contains at least two subpopulations of Esr1+ neurons with different cell body characteristics and locations, with distinct patterns of collateralization to downstream targets. Nevertheless, these projection-defined subpopulations receive similar inputs. This input-output organization appears distinct from those described in other hypothalamic nuclei.

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Lo, L., Kim, D.-W., Yao, S., Cetin, A., Harris, J., Zeng, H., Anderson, D. J., Weissbourd, B.. 2018-10-16. Connectional architecture of a mouse hypothalamic circuit node controlling social behavior. https://doi.org/10.1101/445312

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