Neuroendocrine circuits for engagement in affiliative social interactions

Engaging in affiliative social interactions predicts health and longevity. The hormone oxytocin,
which is released by specialized neurons in the hypothalamus, has been shown to play an
important role in affiliative behaviors. However, the mechanisms that control activity of oxytocin
neurons and by which these neurons might then control engagement in social interactions, have
not yet been elucidated. Our long-term goal is to dissect the neuroendocrine mechanisms driving
voluntary engagement in affiliative social interactions. Our findings will facilitate the design of
therapeutic interventions aimed at addressing the widening loneliness pandemic, as well as ASD.
The objective of this grant is to characterize the role of oxytocin neuron activity patterns in
initiation and reinforcement of social interactions. The central hypothesis is that spiking activity
in oxytocinergic neural circuits plays a critical role in spontaneous and stress-induced social
engagement, and that activity in distinct oxytocinergic circuits specifically controls either initiation
or reinforcement of social engagement. In our specific aims we will use automated behavioral
analysis of video recordings of mice living together for days, behaviorally synchronized neuronal
recordings, optogenetics and chemogenetics to determine if neuronal activity of identified oxytocin
neurons predicts or tracks social interactions (AIM 1). We will use optogenetics and
chemogenetics to manipulate neuronal activity of specific oxytocinergic circuits to determine if
they are required for the initiation or reinforcement of affiliative interactions (AIM 2). We will test if
stressful contexts increase activity in specific oxytocinergic neurons to promote engagement in
affiliative social interactions, as a defensive mechanism (AIM 3). Our work will significantly
contribute to the field, as it will establish mechanisms that can be therapeutically targeted to
drive social engagement. The proposed research is innovative because we investigate activity
patterns in neuroendocrine circuits that predict spontaneously initiated and reinforced social
interactions, which has not been done before. Our results will lay the bases for novel behavioral
interventions and medications that could be used to prevent the negative effects of social
isolation.

Grant Number: 5R01MH128688-04
NIH Institute/Center: NIH
Principal Investigator: Ioana Carcea