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Oxytocin Receptors are expressed on Neurons within the Prefrontal Cortex that Control Preference for Social Novelty
Author(s) -
Tan Yalun,
Singhal Sarthak,
Hiller Helmut,
Nguyen DanTam,
ColonPerez Luis M.,
Febo Marcelo,
Wang Lei,
Kloet Annette D.,
Frazier Charles J.,
Krause Eric G.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1076.13
Subject(s) - optogenetics , oxytocin receptor , neuroscience , ventral pallidum , nucleus accumbens , oxytocin , glutamatergic , ventral tegmental area , basolateral amygdala , channelrhodopsin , prefrontal cortex , biology , amygdala , glutamate receptor , basal ganglia , receptor , globus pallidus , dopamine , central nervous system , dopaminergic , cognition , biochemistry
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)