Áreas olfativas são alvos do isolamento social: implicações na memória social e no sistema oxitocinérgico

Abstract

The ability to recognize and appropriately respond to social stimuli is essential for the formation and maintenance of intraspecific interactions in gregarious species. Evidence suggests that social isolation (SI) impairs social recognition, a cognitive process crucial for modulating these interactions. However, the neurobiological mechanisms underlying this impairment remain incompletely understood. This study aimed to investigate whether SI impairs the accuracy of social odor recognition and to identify SI-induced alterations in the olfactory and oxytocinergic systems. In the social acuity task, we found that isolated mice lost the ability to distinguish between familiar and novel social stimuli. Based on electrophysiological recordings from the olfactory bulb (OB), we differentiated mitral cells (MCs) and tufted cells (TCs) by membrane resistance values. We observed that SI reduced the rheobase in MCs and, in TCs, made the membrane potential more negative, while also increasing rheobase and the latency for action potential firing in response to depolarizing currents. SI did not affect spontaneous excitatory and inhibitory postsynaptic currents in TCs, nor the number of tyrosine hydroxylase (TH)-positive cells in the OB. We also analyzed the mRNA expression of oxytocin (OXT) and its receptors (OXTRs) in the paraventricular nucleus of the hypothalamus (PVN) following SI, but found no significant alterations between the groups. However, grouped mice that expressed social memory had more OXT-immunoreactive cells in the PVN than those subjected to SI. In the anterior olfactory nucleus (AON), mRNA levels of OXTRs were also unaffected by SI. Intraperitoneal and intra-AON administration of OXT before the social recognition test reversed the social memory deficit induced by isolation. However, administering OXT before and after training did not have the same effect. In the resocialization test, we observed that 7 days of reaggregation restored social memory. Chemogenetic activation of OXT+ neurons in oxytocin-Cre mice impaired social memory in grouped mice without affecting the memory of isolated mice. Using the retrograde tracer Cholera Toxin B (CTB) injected into the AON, we identified projecting neurons in the reuniens nucleus of the thalamus, but no oxytocinergic neurons were labeled in the PVN. Using the AAV-Syn-EYFP virus unilaterally as an anterograde tracer in the PVN, we observed that SI increased the axon density projecting to the dorsal region of the AON. This study reveals that the olfactory and oxytocinergic systems are sensitive to SI, and alterations in these systems are associated with impairments in social memory.