Medial preoptic area antagonistically mediates stress-induced anxiety and parental behavior

Abstract

Anxiety is a negative emotional state that is overly displayed in anxiety disorders and depression. Although anxiety is known to be controlled by distributed brain networks, key components for its initiation, maintenance and coordination with behavioral state remain poorly understood. Here, we report that anxiogenic stressors elicit acute and prolonged responses in glutamatergic neurons of mouse medial preoptic area (mPOA). These neurons encode extremely negative valence, and mediate induction and expression of anxiety-like behaviors. Conversely, mPOA GABAergic neurons encode positive valence and produce anxiolytic effects. Such opposing roles are mediated by their competing local interactions and long-range projections to the periaqueductal gray. The two neuronal populations antagonistically regulate anxiety-like and parental behaviors: anxiety is reduced while parenting is enhanced and vice versa. Thus, by evaluating negative and positive valences through distinct but interacting circuits, mPOA coordinates emotional state and social behavior.Anxiety is a state of apprehension associated with heightened arousal and vigilance 1-3 . Anxiety after exposure to stress is an adaptive response, as the anxious state helps the animal maintain caution and cope better with future threats. However, anxiety can become *

An Inhibitory Medial Preoptic Circuit Mediates Innate Exploration

“…A previous study showed that vgat neurons, a subset of GABAergic neurons, in the MPA encode positive value ( Zhang et al, 2021 ). Indeed, we recapitulated the results from the RTPP and open field tests in this study.…”

“…Although these results may tentatively suggest that MPA vgat –vPAG is not necessary for exploration, it is important to note that our experiments did not include other stimuli during the test. Previous studies on the function of MPA neurons projecting to the vPAG have shown that these neurons respond to particular stimuli, such as CaMKIIα neurons responding to an object or prey, vglut2 neurons responding to stress, and galanin neurons responding to pups ( Wu et al, 2014 ; Kohl et al, 2018 ; Park et al, 2018 ; Zhang et al, 2021 ). Thus, it is plausible that there will be certain stimuli or conditions that could cause activation in the MPA vgat –vPAG circuit that in turn facilitate exploration.…”

“…Although studies addressing extrinsic exploration toward goals such as feeding ( Viskaitis et al, 2017 ; Tryon and Mizumori, 2018 ; Hao et al, 2019 ), predation ( Han et al, 2017 ; Li et al, 2018 ; Park et al, 2018 ; Shang et al, 2019 ; Zhao et al, 2019 ), and defensive behavior ( Tovote et al, 2016 ; Evans et al, 2018 ; Li et al, 2018 ; Rozeske et al, 2018 ; Zhang et al, 2021 ) have been conducted, those that address intrinsic exploration have been lacking.…”

“…The medial preoptic area (MPA) is part of the anterior hypothalamus and has been implicated in playing a role in many types of innately motivated behavior, such as hunting ( Park et al, 2018 ), anxiety ( Zhang et al, 2021 ), reproductive ( Wei et al, 2018 ; McHenry et al, 2017 ), and parental behavior ( Wu et al, 2014 ; Kohl et al, 2018 ; Li et al, 2019 ; Zhang et al, 2021 ). Although such studies have also shown to a degree the capability of the MPA to increase extrinsic exploration, due to alterations in underlying homeostatic drives or reproductive drives, the potential role of the MPA in modulating intrinsic exploration has received little attention.…”

“…Although such studies have also shown to a degree the capability of the MPA to increase extrinsic exploration, due to alterations in underlying homeostatic drives or reproductive drives, the potential role of the MPA in modulating intrinsic exploration has received little attention. A recent study ( Zhang et al, 2021 ) showed that optogenetic activation of vgat neurons in the MPA is capable of increasing time spent in the stimulated side of a real-time place preference (RTPP). However, this experiment by itself fails to distinguish between intrinsic and extrinsic exploration, since changes seen in RTPP could be driven either due to changes in exploratory behavior itself or due to a reinforcing effect.…”