Abstract

The interconnection between the medial prefrontal cortex (mPFC) and the dorsal raphe nucleus (DR) is involved in mood regulation and stress tolerance. The infralimbic (IL) compartment of the mPFC is the rodent equivalent of the ventral anterior cingulate cortex, which is closely associated with the pathophysiology/treatment of major depressive disorder (MDD). Increased excitatory neurotransmission in the IL, but not in the prelimbic cortex PrL, causes depressiveor antidepressant-like behaviors in rodents associated with altered serotonergic (5-HT) neurotransmission. Therefore, we examined regulation of 5-HT activity by both his mPFC subsets in anesthetized rats. Electrical stimulation of IL and PrL at 0.9 Hz similarly inhibited 5-HT neurons (53% vs. 48%). However, stimulation at higher frequencies (10–20 Hz) revealed a higher proportion of 5-HT neurons that were more sensitive to IL than PrL stimulation (86% vs. 59% at 20 Hz), suggesting that GABAA Different involvement (not 5). -HT1A) receptor. Similarly, electrical and optogenetic stimulation of IL and PrL enhanced 5-HT release in the DR in a frequency-dependent manner, with a greater increase following IL stimulation at 20 Hz. It differentially regulates serotonin activity, apparently playing a superior role. IL, an observation that may help clarify brain circuits involved in MDD.