BDNF and major depressive disorder: 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.