Central amygdala-substantia nigra pars compacta circuit mediates anxiety- and depression-like behaviors in MPTP-treated mice.

Parkinson's disease (PD) is characterized by progressive degeneration of substantia nigra pars compacta (SNc) dopamine (DA) neurons, leading to motor dysfunction. Non-motor symptoms of PD, such as neuropsychiatric symptoms (anxiety and depression), often precede motor symptoms and seriously affect quality of life, but the mediating mechanism has not been well understood. The SNc receives input from somatostatin (SOM) neurons in the central amygdala (CeA), which convey reward related information. This study demonstrated that optogenetic activation of CeA^SOM-SNc circuit induced real-time place preference (RTPP) and alleviated anxiety-like behaviors caused by acute stress. SOM neurons in the CeA preferentially targeted GABAergic neurons in the SNc, optogenetic activation of CeA^SOM-SNc may activate TH neurons in the SNc through disinhibition. The response of CeA neurons to reward was blunted in MPTP-treated mice, and chronic chemogenetic silencing of CeA-SNc induced anxiety- and depression-like behaviors in mice. Furthermore, chronically chemogenetic activation of CeA^SOM-SNc or DA neurons in SNc alleviated anxiety- and depression-like behaviors in MPTP-treated mice. Reward-based chocolate intervention alleviated depression-like behaviors of MPTP-treated mice. In summary, our results indicate that the CeA^SOM-SNc circuit may mediate anxiety- and depression-like behaviors by regulating the activity of SNc DA neurons.