Abstract
Social isolation during the juvenile critical window is detrimental to proper functioning of the prefrontal cortex (PFC) and establishment of appropriate adult social behaviors. However, the specific circuits that undergo social experience-dependent maturation to regulate social behavior are poorly understood. We identify a specific activation pattern of parvalbumin-positive interneurons (PVIs) in dorsal-medial PFC (dmPFC) prior to an active bout, or a bout initiated by the focal mouse, but not during a passive bout when mice are explored by a stimulus mouse. Optogenetic and chemogenetic manipulation reveals that brief dmPFC-PVI activation triggers an active social approach to promote sociability. Juvenile social isolation decouples dmPFC-PVI activation from subsequent active social approach by freezing the functional maturation process of dmPFC-PVIs during the juvenile-to-adult transition. Chemogenetic activation of dmPFC-PVI activity in the adult animal mitigates juvenile isolation-induced social deficits. Therefore, social experience-dependent maturation of dmPFC-PVI is linked to long-term impacts on social behavior.
Highlights
Social isolation during the juvenile critical window is detrimental to proper functioning of the prefrontal cortex (PFC) and establishment of appropriate adult social behaviors
As social behavior is composed of a range of highly specific behaviors, we first set out to examine to what extent adult dorsal-medial PFC (dmPFC)-parvalbuminpositive interneurons (PVIs) are recruited during specific aspects of social behaviors
We found that dmPFC-PVI activity was significantly increased after introducing a novel animal, but not a novel object (Fig. 1c–e, Wilcoxon signed-rank test, social: p = 0.03, object: p = 0.25)
Summary
Social isolation during the juvenile critical window is detrimental to proper functioning of the prefrontal cortex (PFC) and establishment of appropriate adult social behaviors. Inhibitory GABAergic interneurons are a diverse population, made up of several sub-types with distinct connectivity, morphology, and physiology[12] One such sub-type, molecularly defined by the expression of the calciumbinding protein parvalbumin (PV), shows an extended period of development[10,13] and is a known regulator of experience-dependent cortical development in primary sensory cortex[14]. While much evidence implicates dmPFC-PVI dysfunction in humans and in animal models of neurodevelopmental disorders with social deficits[5], few studies have directly interrogated how social experience during development regulates PVI maturation and adult behavioral function. To establish dmPFC-PVIs as circuit targets for amelioration of social behavior deficits, it is essential to identify specific aspects of social behavior coupled with dmPFC-PVIs activity, and to assess whether dmPFCPVIs undergo experience-dependent maturation to govern adult social behavior. We show dmPFC-PVI development is affected by social experience during a juvenile critical window, resulting in disrupted activity patterns of dmPFC-PVIs and subsequent social behavior deficits
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