Social recognition in mammals is a complex biological process that necessitates communication between neural circuits mediating cognitive processes such as discrimination of social stimuli and those underlying expression of affiliation or avoidance behaviors. Circuit alterations that impair social discrimination, social interaction or linkage of social discrimination with social interaction may underlie social recognition deficits seen in autism spectrum disorders and other psychiatric disorders. One general mechanism by which distinct behaviors such as reward seeking, social exploration and discrimination of social stimuli are orchestrated is through the actions of neuromodulators such as oxytocin (OT). Although a growing number of studies have begun to shed light on oxytocin receptor (Oxtr) signaling in the nucleus accumbens, lateral septum and prefrontal cortex in social interaction, the contribution of Oxtrs in the hippocampus to social memory is not known. This proposal seeks to identify (i) fundamental circuit mechanisms by which hippocampal Oxtr signaling promotes discrimination of social stimuli and, (ii) the neural pathways that link these computations with circuits that subserve social interaction. Towards these goals, we will harness viral and mouse conditional genetic tools, optogenetics, cellular ensemble imaging and behavior to precisely manipulate hippocampal Oxtr signaling with unprecedented spatial and temporal control and determine its contributions to social recognition. Insights gleaned from the proposed studies will shed light on how an ancient neuromodulator like OT has evolved to utilize basic memory-processing circuit mechanisms to perform discrimination of social stimuli. The significance of the studies lies in its potential to illuminate fundamental neural mechanisms underlying previously unrecognized roles of hippocampal Oxtr signaling in social recognition. Ultimately, these mechanisms may guide novel therapeutic strategies for promoting social recognition in disorders in which it is impaired.

Public Health Relevance

Social recognition deficits characterize autism spectrum disorders and other psychiatric disorders. The proposed studies will investigate the neural circuit mechanisms and pathways by which hippocampal oxytocin receptors contribute to social recognition. An understanding of these mechanisms may guide novel therapeutic strategies for promoting social recognition in disorders in which it is impaired.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Neurobiology of Motivated Behavior Study Section (NMB)
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Breeden, Andrew Lee
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Massachusetts General Hospital
United States
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Guo, Nannan; Soden, Marta E; Herber, Charlotte et al. (2018) Dentate granule cell recruitment of feedforward inhibition governs engram maintenance and remote memory generalization. Nat Med 24:438-449
Raam, Tara; McAvoy, Kathleen M; Besnard, Antoine et al. (2017) Hippocampal oxytocin receptors are necessary for discrimination of social stimuli. Nat Commun 8:2001