RT Journal Article
SR Electronic
T1 Social Stimuli Induce Activation of Oxytocin Neurons Within the Paraventricular Nucleus of the Hypothalamus to Promote Social Behavior in Male Mice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2282
OP 2295
DO 10.1523/JNEUROSCI.1515-18.2020
VO 40
IS 11
A1 Shanna L. Resendez
A1 Vijay Mohan K. Namboodiri
A1 James M. Otis
A1 Louisa E.H. Eckman
A1 Jose Rodriguez-Romaguera
A1 Randall L. Ung
A1 Marcus L. Basiri
A1 Oksana Kosyk
A1 Mark A. Rossi
A1 Gabriel S. Dichter
A1 Garret D. Stuber
YR 2020
UL http://www.jneurosci.org/content/40/11/2282.abstract
AB Oxytocin (OT) is critical for the expression of social behavior across a wide array of species; however, the role of this system in the encoding of socially relevant information is not well understood. In the present study, we show that chemogenetic activation of OT neurons within the paraventricular nucleus of the hypothalamus (PVH) of male mice (OT-Ires-Cre) enhanced social investigation during a social choice test, while chemogenetic inhibition of these neurons abolished typical social preferences. These data suggest that activation of the OT system is necessary to direct behavior preferentially toward social stimuli. To determine whether the presence of a social stimulus is sufficient to induce activation of PVH-OT neurons, we performed the first definitive recording of OT neurons in awake mice using two-photon calcium imaging. These recordings demonstrate that social stimuli activate PVH-OT neurons and that these neurons differentially encode social and nonsocial stimuli, suggesting that PVH-OT neurons may act to convey social salience of environmental stimuli. Finally, an attenuation of social salience is associated with social disorders, such as autism. We therefore also examined possible OT system dysfunction in a mouse model of autism, Shank3b knock-out (KO) mice. Male Shank3b KO mice showed a marked reduction in PVH-OT neuron number and administration of an OT receptor agonist improved social deficits. Overall, these data suggest that the presence of a social stimulus induces activation of the PVH-OT neurons to promote adaptive social behavior responses.SIGNIFICANCE STATEMENT Although the oxytocin (OT) system is well known to regulate a diverse array of social behaviors, the mechanism in which OT acts to promote the appropriate social response is poorly understood. One hypothesis is that the presence of social conspecifics activates the OT system to generate an adaptive social response. Here, we selectively recorded from OT neurons in the paraventricular hypothalamic nucleus (PVH) to show that social stimulus exposure indeed induces activation of the OT system. We also show that activation of the OT system is necessary to promote social behavior and that mice with abnormal social behavior have reduced numbers of PVH-OT neurons. Finally, aberrant social behavior in these mice was rescued by administration of an OT receptor agonist.