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Science Translational Medicine  22 Feb 2017:
Vol. 9, Issue 378, eaam6067
DOI: 10.1126/scitranslmed.aam6067


Reproductive hormones alter activity in neural circuits linking reward and social interactions.

In their natural environment, animals must balance the often conflicting demands of food, safety, and reproduction. External cues, such as sounds and odors, regulate social interactions, but these are also modulated by internal hormonal signals. How external and internal information is integrated in these circuits is largely unknown. Now, McHenry et al. have shown how reproductive hormones regulate neural circuits to increase social interactions.

Previous work describes a circuit linking the forebrain medial preoptic area (mPOA) to the midbrain ventral tegmental area (VTA) that is critical for reproductive behavior. In their initial studies, McHenry and coauthors found that most neurons in this circuit express estrogen receptors and the neuropeptide neurotensin (NTS). In vivo imaging of the mPOA in female mice revealed a subset of NTS neurons that were specifically activated by the odor of male urine and when treated with a reproductive hormone, estradiol, increased both the number of activated cells and the individual cell responses to this odor. Estradiol treatment altered the proportion of cell-surface ion channels in these cells, allowing them to fire more frequently. Next, the authors mimicked the effects of male odors by using optogenetics to activate NTS neurons in the mPOA. Switching on these neurons was rewarding to the mice and modified their social interactions. Male mice spent more time interacting with females, but female mice only increased their interactions with males when they also received treatment. In addition, switching on mPOA neurons increased dopamine release in brain regions known to be involved in reward and addiction, and estradiol amplified this effect. Last, the authors showed that silencing NTS neurons in estradiol-treated female mice reduced their interactions with male but not female mice, showing that NTS neurons were a key part of this circuit.

These studies suggest that in female mice, estradiol modulates the excitability of a neural circuit regulating social behavior to enhance interactions with males. If these cells and circuits play a similar role in humans, it would be important to know how reproductive hormones affect them. These studies might provide insight into the observation that affective disorders can increase during puberty, pregnancy, and perimenopause.

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