Volume 31, Issue S1 p. 1076.13-1076.13
Physiology
Free Access

Oxytocin Receptors are expressed on Neurons within the Prefrontal Cortex that Control Preference for Social Novelty

Yalun Tan

Yalun Tan

Department of Pharmacodynamics, University of Florida, Gainesville, FL

Search for more papers by this author
Sarthak Singhal

Sarthak Singhal

Department of Pharmacodynamics, University of Florida, Gainesville, FL

Search for more papers by this author
Helmut Hiller

Helmut Hiller

Department of Pharmacodynamics, University of Florida, Gainesville, FL

Search for more papers by this author
Dan-Tam Nguyen

Dan-Tam Nguyen

College of Pharmacy, University of Florida, Gainesville, FL

Search for more papers by this author
Luis M. Colon-Perez

Luis M. Colon-Perez

Department of Psychiatry, University of Florida, Gainesville, FL

Search for more papers by this author
Marcelo Febo

Marcelo Febo

Department of Psychiatry, University of Florida, Gainesville, FL

Search for more papers by this author
Lei Wang

Lei Wang

Department of Pharmacodynamics, University of Florida, Gainesville, FL

Search for more papers by this author
Annette D. de Kloet

Annette D. de Kloet

Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL

Search for more papers by this author
Charles J. Frazier

Charles J. Frazier

Department of Pharmacodynamics, University of Florida, Gainesville, FL

Search for more papers by this author
Eric G. Krause

Eric G. Krause

Department of Pharmacodynamics, University of Florida, Gainesville, FL

Search for more papers by this author

Abstract

Oxytocin is a promising therapeutic for social impairments associated with neuropsychiatric conditions; however, the precise brain circuits influenced by oxytocin remain unknown. The prefrontal cortex (PFC), which exerts top-down control over various subcortical regions, densely expresses oxytocin receptors (OTR) that may mediate the effects of oxytocin on social behavior. Here, we use the Cre-LoxP system in mice with anatomical, electrophysiological, imaging and optogenetic approaches to discern how ‘oxytocin sensitive’ neurons in the PFC may influence social behaviors. Male mice with expression of Cre recombinase driven by the promoter for the OTR gene (OTR-Cre mice) were delivered Cre-inducible adeno associated virus producing channel rhodopsin-2 and enhanced yellow fluorescent protein (AAV-ChR2-eYFP) into the PFC. Viral delivery revealed that 54% and 27% of OTR-expressing neurons in the PFC were glutamatergic or GABAergic, respectively. Retrograde tract-tracing, in conjunction with in vitro optogenetics, found that OTR-expressing PFC neurons sent glutamatergic projections to the nucleus accumbens, bed nucleus of the stria terminalis and basolateral amygdala (BLA). Functional magnetic resonance imaging confirmed that in vivo photo-stimulation of OTR-expressing neurons evoked increased activation of the PFC and downstream subcortical regions including the BLA. To assess the function of OTR-expressing PFC neurons, OTR-Cre mice were administered AAV-ChR2-eYFP or control virus and chronically implanted with fiber optics targeting the PFC. Subsequently, mice were evaluated in the social interaction (SI) and social novelty paradigms, novel object recognition test, elevated plus maze (EPM) and open field (OF). In vivo optogenetic stimulation of OTR-expressing PFC neurons abolished preference for social novelty (n=6 per group; Control: P<0.01; ChR2: P=0.4), but had no effect on anxiety-like behavior in the EPM, OF, or SI test. Locomotor activity and novel object recognition were also not affected. Collectively, our results suggest that excitation of OTR-expressing neurons in the PFC exerts top-down control over brain circuits controlling preference for social novelty.

Support or Funding Information

National Heart, Lung, and Blood Institute Grant HL122494 (Eric G Krause); National Institute of Mental Health Grant MH104641 (Charles J Frazier)