mPFC DCC coupling with CaMKII+ neuronal excitation participates in behavioral despair in male mice

• DOI: 10.1038/s41398-025-03266-x
• Publication Date: 2025-02-14T18:23:03Z
• Authors: Ping Cheng; Keke Ding; Daokang Chen; Chen Yang; Juan Wang; Shaojie Yang; Ming Chen; Guoqi Zhu
• Keywords: Neurosciences. Biological psychiatry. Neuropsychiatry; RC321-571

A longed lack of control over harmful stimuli can lead to learned helplessness (LH), a significant factor in depression. However, the cellular and molecular mechanisms underlying LH, eventually behavioral despair, remain largely unknown. The deleted colorectal cancer (dcc) gene is associated with risk therapeutic potential regulation mechanism DCC despair are still uncertain. In this study, we showed that depressive stimulators, including lipopolysaccharide, unpredictable chronic mild stress, triggered an elevation expression medial prefrontal cortex (mPFC). Additionally, elevated mPFC was crucial inducing as evidenced by induction normal mice exacerbation LH upon overexpression. By contrast, neutralizing activity ameliorated LH-induced despair. Importantly, elucidated pathological attributable excessive excitation CaMKII+ neurons manner dependent on calpain-mediated degradation SCOP aberrant phosphorylation ERK signaling pathway. addition, increase led decreased excitability threshold mPFC, which supported observation ligand netrin 1 increased frequency action firing spontaneous excitatory postsynaptic currents neurons. conclusion, our data indicate triggers activation calpain-SCOP/ERK promote expression, represents target for treatment male mice.