Dynamic encoding of social threat and spatial context in the hypothalamus

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.

Differential Encoding of Predator Fear in the Ventromedial Hypothalamus and Periaqueductal Grey

“…A potential role for VMHdm in encoding defensive motivation is also supported by analogy with single unit electrophysiological recordings and calcium imaging in the ventrolateral division of the VMH (VMHvl), a part of the medial hypothalamic reproductive system, in male mice exhibiting aggression toward male intruders (Lin et al, 2011;Falkner et al, 2014Falkner et al, , 2016Remedios et al, 2017;Krzywkowski et al, 2020). In these studies, VMHvl neurons showed increased firing when exposed to awake males, anesthetized males, or male urine, and the intensity of activation was correlated with the latency and duration of future attacks, demonstrating the encoding of both sensory as well as motivational features of the behavior.…”

Mapping the neural circuitry of predator fear in the nonhuman primate

“…Our findings have two important implications for our understanding of fear in humans. First, our discovery makes it likely that the medial hypothalamus plays a similar role in encoding an internal state of threat in primates as it does in rodents (Kunwar 2015 ; Silva et al 2016a ; Esteban Masferrer et al 2018 ; Krzywkowski et al 2019 ; Masferrer et al 2018 ; Kennedy et al 2019 ). Notably, VMHdm in rodents is required for the induction and expression of both innate and conditioned predator fear (Silva et al 2013 , 2016 ; Kunwar 2015 ) and stimulation of VMHdm in monkeys and humans is sufficient to elicit an intense defensive emotional state (Wilent 2010 ; Lipp and Hunsperger 1978 ).…”

Neural Circuits Underlying Social Fear in Rodents: An Integrative Computational Model

“…Finally, we ran the simulations to fit the experimental data. We observed that, to reproduce the experiment of Krzywkowski et al (2020), the connection between vHIP and VMHvl had to be made plastic. This corresponds to a principle of parsimony aimed at simplifying the model, staying as much as possible grounded on literature, and minimizing the hypothesis.…”

“…This led to a more powerful activation of the Pyr2 fear-OFF population, compared to the non manipulated control, and to a consequent deactivation of the Pyr1 fear-ON population (Figures 5D,E). Krzywkowski et al (2020) studied the activation of different VMHvl populations during the aversive social encounter and when the mice were re-exposed to the same context without the opponent. Their Defeat+ population corresponds to our threat unit Hyp1, which is active during, but not before, conditioning (Figure 5F; see also Figure 2B).…”

“…An alternative protocol to avoid unspecific symptoms, also known as social fear conditioning, consists of pairing the social investigation of a conspecific with a foot shock, akin to what is done in auditory fear conditioning (Toth et al, 2012(Toth et al, , 2013. After these protocols the defeated animal displays avoidance of conspecifics, measured as more time spent freezing and in defensive postures, less time spent investigating the conspecific and a higher number of sudden retreats from the investigation (Toth et al, 2012(Toth et al, , 2013Franklin et al, 2017;Xu et al, 2019;Krzywkowski et al, 2020).…”