Social animals expend considerable energy to maintain social bonds throughout their life. Male and female mice show sexually dimorphic behaviors, yet the underlying neural mechanisms of sociability and their dysregulation during social disconnection remain unknown. Dopaminergic neurons in dorsal raphe nucleus (DRN TH ) is known to contribute to a loneliness-like state and modulate sociability. We identified that activated subpopulations in DRN TH and nucleus accumbens shell (NAc sh ) during 24 hours of social isolation underlie the increase in isolation-induced sociability in male but not in female mice. This effect was reversed by chemogenetically and optogenetically inhibiting the DRN TH -NAc sh circuit. Moreover, synaptic connectivity among the activated neuronal ensembles in this circuit was increased, primarily in D 1 receptor–expressing neurons in NAc sh . The increase in synaptic density functionally correlated with elevated dopamine release into NAc sh . Overall, specific synaptic ensembles in DRN TH -NAc sh mediate sex differences in isolation-induced sociability, indicating that sex-dependent circuit dynamics underlie the expression of sexually dimorphic behaviors.

Ketamine, a non-competitive antagonist of the N-methyl-d-aspartate receptor (NMDAR), generates a rapidly-acting antidepressant effect. It exerts psychomimetic effects, yet demands a further investigation of its mechanism. Previous research showed that ketamine did no longer promote hyperlocomotion in GluN2D knockout (KO) mice, which is a subunit of NMDAR. In the present study, we tested whether GluN2D-containing NMDARs participate in the physiological changes in the medial prefrontal cortex (mPFC) triggered by ketamine. Sub-anesthetic dose of ketamine (25 mg/kg) elevated the frequency of spontaneous excitatory postsynaptic currents (sEPSC) in wild-type (WT) mice, but not in GluN2D KO mice, 1 h after the injection. The amplitude of sEPSC and paired-pulse ratio (PPR) were unaltered by ketamine in both WT and GluN2D KO mice. These findings suggest that GluN2D-containing NMDARs might play a role in the ketamine-mediated changes in glutamatergic neurons in mPFC and, presumably, in ketamine-induced hyperlocomotion.

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The hippocampus is one of the most widely investigated brain regions with its massive contributions to multiple behaviours. Especially, the hippocampus is subdivided into the dorsal and ventral parts playing distinct roles. In this review, we will focus on the ventral hippocampus, especially the ventral CA1 (vCA1), whose role is being actively discovered. vCA1 is well known to be associated with emotion-like behaviour, in both positive (reward) and negative (aversive) stimuli. How can this small region in volume mediate such variety of responses? This question will be answered with technologies up to date that have allowed us to study in-depth the specific neural circuit and to map the complex connectivity.