Activity in the dorsal hippocampus-mPFC circuit modulates stress-coping strategies during inescapable stress.
Experimental & molecular medicine September 1, 2024 Sang Ho Yoon, Woo Seok Song, Geehoon Chung et al. 14 citations
Neuronal activity in the dorsal hippocampus (dHP) influences how mice cope with inescapable stress, acting through excitatory connections to the medial prefrontal cortex (mPFC). The antidepressant ketamine rapidly activates both dorsal and ventral hippocampi. Suppressing GABAergic transmission in the dHP produces molecular changes similar to ketamine's effects—including dephosphorylation of eEF2, elevation of BDNF, and phosphorylation of ERK—and reduces immobility in tail-suspension and forced swim tests without affecting anxiety. Conversely, enhancing inhibitory transmission in the dHP CA1 region induces passive coping. Chemogenetic activation of dHP-recipient mPFC neurons reverses this passive coping, suggesting the dHP-mPFC circuit modulates stress-coping strategies and contributes to ketamine's antidepressant action.