Dynamic encoding of social threat and spatial context in the hypothalamus.

Piotr Krzywkowski,Beatrice Penna,Cornelius T Gross

doi:10.7554/elife.57148

Piotr Krzywkowski, Beatrice Penna + Show 1 more

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https://doi.org/10.7554/elife.57148

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Abstract

Social aggression and avoidance are defensive behaviors expressed by territorial animals in a manner appropriate to spatial context and experience. The ventromedial hypothalamus controls both social aggression and avoidance, suggesting that it may encode a general internal state of threat modulated by space and experience. Here, we show that neurons in the mouse ventromedial hypothalamus are activated both by the presence of a social threat as well as by a chamber where social defeat previously occurred. Moreover, under conditions where the animal could move freely between a home and defeat chamber, firing activity emerged that predicted the animal's position, demonstrating the dynamic encoding of spatial context in the hypothalamus. Finally, we found that social defeat induced a functional reorganization of neural activity as optogenetic activation could elicit avoidance after, but not before social defeat. These findings reveal how the hypothalamus dynamically encodes spatial and sensory cues to drive social behaviors.

Highlights

Comparative molecular and functional studies across animal species demonstrate that the hypothalamus contains evolutionarily conserved brain networks for controlling survival behaviors and maintaining physiological homeostasis (Swanson, 2000; Tosches & Arendt, 2013)
In order to better understand what aspects of defense are encoded in VMHvl neuron firing, we used in vivo microendoscopic calcium imaging to measure neuronal response properties in mice subjected to social defeat (Figure 1a-e)
By performing single unit in vivo recordings during social defeat as well as during the postdefeat approach-avoidance period, again during re-exposure to the threat context one day later, and during resident-intruder aggression we were able to examine the encoding of social threat in the VMHvl across a wide variety of defensive behaviors

Summary

Introduction

Comparative molecular and functional studies across animal species demonstrate that the hypothalamus contains evolutionarily conserved brain networks for controlling survival behaviors and maintaining physiological homeostasis (Swanson, 2000; Tosches & Arendt, 2013). Consistent with a general role in social threat responding electrical, pharmacogenetic, or optogenetic stimulation of VMHvl is able to elicit or increase the probability of social aggression (Olivier, 1977; Kruk et al, 1983; Lin et al, 2011; Lee et al., 2014; Hashikawa et al, 2017; Yang et al, 2017; Wang et al, 2019) and avoidance (Sakurai et al, 2016; Wang et al, 2019). These responses are often unreliable and have been shown to be influenced by the social and hormonal status of both the subject and the threat (Lin et al, 2011; Lee et al, 2014; Sakurai et al, 2016; Yang et al, 2017) suggesting a role for past experience or other environmental factors in dictating the behavioral output of VMHvl

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