Dynamic regulation of oxytocin neuronal circuits in the sequential processes of prosocial behavior in rodent models

Abstract

The expression of positive social (i.e., prosocial) behavior is governed by a multitude of sensory and cognitive abilities to identify and recognize key features of potential social partners, elucidate social and individual status, and maintain appropriate behaviors. Oxytocin (OT) is a neuropeptide that has been implicated as a major player in regulating prosocial behavior, and much of its role in social situations has been uncovered. As social behavior inherently comprises sequential processes related to multimodal assessments of interactive features, a comprehensive approach to understanding the functions of OT in these prosocial behavior sequences is required. Here, the author discusses recent evidence illustrating the functioning of OT neural circuits in the processing of multimodal components of social behavior, including the detection/recognition of social cues via the olfactory bulb through olfactory cortices, evaluation of social features via the circuits of the paraventricular nucleus of the hypothalamus to the medial amygdala, and maintenance of prosocial behaviors via the circuits of the ventral tegmental area to the nucleus accumbens. A review of rodent studies with an emphasis on mice and rats is also provided to investigate the effects of OT in interaction with other neurotransmitters, such as serotonin and dopamine, to characterize the neuromodulatory mechanisms that mediate the sequences of prosocial engagements. The review further highlights OT function as a temporal dynamic of specific neural circuits.

Keywords: Amygdala; Behavioral sequence; Hypothalamus; Neural circuits; Olfactory bulb; Oxytocin; Prosocial behavior; Raphe nucleus; Ventral tegmental area.

Graphical abstract

Fig. 1

A diagram of the relationships between familiarity and behavioral strategies towards social encounters. At a distance, volatile olfactory signals are detected, which activates exploratory behavior. In a proximity, risk assessment behavior is performed to gather more information regarding social features of social stimuli via non-volatile and tactile signals. When getting familiar with the social stimulus, staying in the proximity and body contact are permitted each other, and thus, time spent in proximity/contact is increased.

Fig. 2

Olfactory circuity coordinated with OT neurons in mouse ventral brain. Volatile odorants as a social signal are processed via the main olfactory epithelium (MOE), olfactory bulb (OB), olfactory and piriform cortex (PC) mediodorsal thalamus (MD), amygdala (Amyg), and Entorhinal cortex (EC) and hippocampus (HPC). Nonvolatile odorants as a contact social signal are processed through the vomeronasal organ (VNO), accessary olfactory bulb (AOB), and medial amygdala (MeA). OT neurons innervate from the paraventricular nucleus of hypothalamus (PVN) to several brain sites associated with these olfactory processes.

Fig. 3

OT neural circuits regulating multiple processes of prosocial behaviors. When sensory inputs associated with social stimuli are delivered via the sensory systems, including olfactory and tactile senses, the OT neurons in the paraventricular nucleus of the hypothalamus (PVN) consist of two discrete cell types (e.g., magnocellular and parvocellular neurons) and the serotonergic neurons in the raphe nucleus are stimulated. OT neurons innervate with several brain sites, including the olfactory bulb-cortices, raphe nucleus, amygdala complex, and ventral tegmental area (VTA) and nucleus accumbens (NAc). 5-HT neurons are also projected to several brain sites associated with OT neurons, including the raphe nucleus, amygdala, and reward circuit (VTA and NAc). The 5-HT and OT in the PVN can activate the release of OT. The OT neurons from the PVN to medial amygdala play a significant role in approach and investigatory behaviors to social stimuli. OT neurons also stimulate the reward circuits of VTA-NAc via dopamine neurons to maintain contact-based social behavior such as huddling. A modulatory circuit including the insular cortex to the bed nucleus of the stria terminalis (BNST) receives OT input integrates sensory social information and sends back modulatory signals to the PVN and reward circuit, providing adaptable behavioral responses in a social situation (evaluation) dependent manner.