Hormonal gain control of a medial preoptic area social reward circuit

Abstract

Neural networks that control reproduction must integrate social and hormonal signals, tune motivation, and invigorate social interactions. However, the neurocircuit mechanisms for these processes remain unresolved. The medial preoptic area (mPOA), an essential node for social behaviors and is comprised of molecularly-diverse neurons with widespread projections. Here, we identify a steroid-responsive subset of neurotensin (Nts) expressing mPOA neurons that interface with the ventral tegmental area (VTA) to form a socially-engaged reward circuit. Using in vivo 2-photon imaging in female mice, we show that mPOANts neurons preferentially encode attractive male cues compared to non-social appetitive stimuli. Ovarian hormone signals regulate both the physiological and cue encoding properties of these cells. Furthermore, optogenetic stimulation of mPOANts-VTA circuitry promotes rewarding phenotypes, social approach, and striatal dopamine release. Collectively, these data demonstrate that steroid-sensitive mPOA neurons encode ethologically-relevant stimuli and co-opt midbrain reward circuits to promote prosocial behavior critical for species survival.

Determination of neurotensin projections to the ventral tegmental area in mice

“…A minor population of GFP cells were noted that did not contain observable Nts-IR. Our data concur with a recent report of dual-label ISH in the Nts Cre line, which showed almost complete overlap of Nts and Cre (McHenry et al, 2017). Taken together, these data verify the fidelity of the Nts Cre ;GFP mouse line and its usefulness to identify and study Nts neurons.…”

“…To our knowledge this is the first comprehensive definition of mouse Nts afferents to the VTA, and is a first step toward understanding how Nts coordinates a diverse repertoire of behaviors in mice. Indeed, since Nts afferents from the MPO and LHA of mice modify DA-mediated social interaction and energy balance, respectively (McHenry et al, 2017; Patterson et al, 2015; Woodworth et al, 2017b) it is possible that each Nts circuit orchestrates a specific motivated behavior via the VTA. Going forward it will be important to determine the particular roles of each Nts projection, and hence precise mechanisms to influence feeding, locomotor activity, social behavior, sleep, and response to addictive drugs.…”

“…The LHA may be just one of several sites by which Nts orchestrates distinct behavioral responses in the mouse VTA, thus it will be important to define all Nts afferents to the VTA and test their roles individually. Indeed, Nts Cre mice were recently used to define how medial preoptic area Nts neurons projecting to the VTA mediate social reward behavior, but this projection does not modify feeding (McHenry et al, 2017). Since these data suggest that distinct sources of mouse Nts coordinate specific DA-mediated behaviors relevant to survival (e.g.…”

Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior

“…In addition to maternal behavior, the MPOA has a number of important homeostatic roles, including thermoregulation, sleep, and social reward (21,22). Potentially, maternal behavior could be impacted if losing the influence of prolactin on these functions also impaired pregnancyrelated adaptations in the maternal brain.…”

“…However, these interactions were not sustained, and the mothers never exhibited full maternal care and abandoned their pups within 24 h of birth. Thus, it seems that prolactin action in the MPOA is necessary for the normal function of the maternal network, possibly altering the key output of the network to regions that reinforce the behavior (22). This might be mediated by prolactin itself but also by the closely related placental lactogens that act on the Prlr and are elevated in the blood throughout the second half of pregnancy (25).…”