For example, the knockdown of BDNF in the dorsolateral PFC (dlPFC) is sufficient to induce MDD‐ and stress‐related phenotypes.[53] While knockdown of BDNF in a brainstem nucleus such as the dorsal raphe nucleus (DRN) resulted in no impairment in depression‐like behaviors as assessed in the FST and SPT.[54, 55, 56] In this study, we demonstrated that optogenetic activation of LCTH neurons induced a marked increase in BDNF protein levels in the dLS and K252a or BDNF‐nAb disrupted the antidepressant‐like effects produced by the activation of the circuit. This evidence concerns the gene BDNF and depressive disorder.