No abstract

Clinical studies have shown that social defeat is an important cause of mood-related disorders, accompanied by learning and memory impairment in humans. The mechanism of mood-related disorders has been widely studied. However, the specific neural network involved in learning and memory impairment caused by social defeat remains unclear. In this study, behavioral test results showed that the mice induced both learning and memory impairments and mood-related disorders after exposure to chronic social defeat stress (CSDS). c-Fos immunofluorescence and fiber photometry recording confirmed that CaMKIIα expressing neurons of the piriform cortex (PC) were selectively activated by exposure to CSDS. Next, chemogenetics and optogenetics were performed to activate PC CaMKIIα expressing neurons, which showed learning and memory impairment but not mood-related disorders. Furthermore, chemogenetic inhibition of PC CaMKIIα expressing neurons significantly alleviated learning and memory impairment induced by exposure to CSDS but did not relieve mood-related disorders. Therefore, our data suggest that the overactivation of PC CaMKIIα expressing neurons mediates CSDS-induced learning and memory impairment, but not mood-related disorders, and provides a potential therapeutic target for learning and memory impairment induced by social defeat.

The mediodorsal thalamus (MD) is interconnected with the medial prefrontal cortex (mPFC) and works together to promote some forms of behavioral flexibility. But the relationship between the MD-mPFC circuit and depression is remain unknown. Here, we show that in male susceptible mice, MDGLU neuronal calcium signaling activity is reduced. Chemogenetic inhibition of MDGLU neuronal in male C57BL/J mice resulted in behavioral abnormalities, whereas in susceptible mice, activation of MDGLU neuronal ameliorated depression-like behavior. Brain slice electrophysiology and fiber optic recordings reveal elevated excitability of mPFCGLU neurons in male susceptible mice. Furthermore, we found that in susceptible mice, mPFCGLU neurons exhibited decreased inhibitory postsynaptic currents and unchanged excitatory postsynaptic currents, and increased E/I ratios, whereas activation of MDGLU neurons restored these electrophysiological properties abnormal. Optogenetic activation of the MD-mPFC circuit ameliorates depression-like behaviors in susceptible mice. Taken together, these data demonstrate that the MD-mPFC circuit controls distinct aspects of depression-like behavior.