News and ReviewsOxytocin and excitation/inhibition balance in social recognition
Introduction
Social cognition is a complex behavior covering all the aspects of processing information about one’s personality and other members of social groups as well as about group dynamics (Bicks et al., 2015). Social recognition (memory of social interactions) is commonly viewed as an ability to discriminate familiar and unfamiliar social objects (Nairne et al., 2012). Social cognition and social recognition, respectively, are critical for analysis and storage of socially meaningful information, therefore, they are required for the maintenance of social groups, interpersonal communications, learning, reproduction, skill acquisition, social decision making, etc. Various manifestations of social cognition and social recognition are combined within social behavioral patterns based on the perception, analysis, forgetting, and recollection of information related to social stimuli. In experimental neurosciences, social cognition and social recognition are usually defined as an interest to novel social objects or a decrease in spontaneous investigation behaviors observed in a rodent re-exposed to a familiar conspecific, respectively (Kogan et al., 2000). Such behavior is based on an ability to find and remember the individual traits that are critical for discrimination within the social group. Several brain disorders are associated with dramatic changes in social behaviors (neurodevelopmental disorders, neurodegeneration, etc.), thus, there is a strong need in studying molecular mechanisms of social recognition and its impairment.
Social recognition is a certain subtype of learning and memory that brings into effective action defined brain regions and molecular pathways recognizable to social cognition (Lopatina et al., 2007). In the last decades, some novel molecular mechanisms involved in social cognition, especially pertaining to the consolidation of memories of particular conspecific organisms, begun to be assessed (Bickle, 2008; Todorov et al., 2006). Several neurotransmitters (glutamate, GABA, acetylcholine, dopamine, steroids, endocannabinoids, etc.), neuropeptides (oxytocin (OT), arginine-vasopressin (AVP), etc.), and brain regions (dorsolateral, medial, or medial prefrontal cortex, amygdala, nucleus accumbens, hypothalamus, hippocampus, posterior middle temporal gyrus) have been implicated in the cognition and memory of social interactions (Ferguson et al., 2002; Grossmann, 2013; Guzmán et al., 2014; Hitti and Siegelbaum, 2014; Mitchell et al., 2005; Sugiura et al., 2014; Weissman et al., 2008).
Human studies demonstrate GABA and OT are remarkably associated with social and cognitive dysfunction related to autism spectrum disorder (Alabdali et al., 2014). Expression data and protein levels show a dysregulation in multiple GABAA and GABAB receptors in key sites of the brain in subjects with autism which could explain several clinical phenotypes including the presence of seizures, learning disabilities and mental retardation (Sesarini, 2015). However, precise mechanisms of social cognition and social recognition remain elusive.
There is a robust proposal that both OT and GABA signaling mediate excitatory–inhibitory (E/I) ratio in the context of brain socialization but molecular pathways are still not clear. In present review, we focused on the underpinning molecular mechanisms and related biomarkers of OT contribution in GABA-mediated E/I ratio in the brain according to the physiological and pathological conditions. We will discuss therapeutic potential of OT in maintaining E/I balance in a context of aberrant social cognition and social recognition.
Section snippets
GABA and synaptic homeostasis
Olfactory, visual, auditory and tactile stimuli are important in inducing social cognition and social recognition, and their actions can be examined in social recognition and/or social discrimination tasks in various protocols (Ferguson et al., 2002) with accompanying assessment of synaptic plasticity (Gur et al., 2014). It should be noted here that mechanisms of stimulus-induced changes in cell excitability and network remodeling are tightly linked to so-called synaptic plasticity which is
Oxytocin action in social recognition: involvement of various brain regions
Current data suggest that the oxytocinergic system is tightly linked to GABA-mediated E/I control in the context of brain socialization. The situation is more complicated in the OT secretory machinery of the hypothalamus: conversion of GABAergic inhibition to excitation was reported previously in AVP and OT neurons in brain slices isolated from rats subjected to the chronic hyperosmotic stress, which is known to stimulate the secretion of these two hormones (Kim et al., 2011). This phenomenon
Social recognition and working memory
Functional magnetic resonance imaging (fMRI) of brain activity in humans subjected to social interactions always confirms involvement of the dorsolateral and ventromedial prefrontal cortex, and amygdala, which are in a strong connection with other brain regions (i.e. ventral striatum, right anterior insula etc.) (Rilling et al., 2008).
In mice analysis of immediate early genes expression induced by social interactions shows that activation depends on the type of social cognition (i.e. sensing
G-protein signaling
Structural plasticity of GABA receptors which is controlled by scaffolding proteins and adhesion molecules greatly affects the inhibitory activity of GABA in the adult brain. The CA2 region of the hippocampus, which is deeply involved in social cognition and social recognition, is highly enriched by GABAergic neurons located in a close connection with pyramidal cells in gender-specific features (Dudek et al., 2016). Therefore, it is expected that the population of inhibitory reelin-expressing
Conclusions and future perspectives in treatment for psychiatric disorders
Consideration of the neural plasticity in respect to E/I balance formation during the different periods of ontogenesis is a long-lasting goal for translational research in the field of mental health in order to provide the best approaches for pharmacotherapy to improve social cognition and social recognition. Results from different studies proposal that oxytocinergic system is related to GABA-mediated E/I control in the context of brain socialization.
The promising effects of neuropeptides,
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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