Thalamic and Medial Prefrontal Cortical Circuits Mediate Social Defeat Stress-Induced Depression-Like Behaviors

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.