Dorsal peduncular cortex activity modulates affective behavior and fear extinction in mice

Abstract

The medial prefrontal cortex (mPFC) is critically involved in cognitive and emotional function and underlies many neuropsychiatric disorders, including mood, fear and anxiety disorders. In rodents, disruption of mPFC activity affects anxiety- and depression-like behavior, with evidence supporting specialized contributions from its subdivisions. The rodent mPFC is often subdivided into the anterior cingular cortex (ACC), prelimbic cortex (PL), and the infralimbic cortex (IL), and broken down into the dorsomedial prefrontal cortex (dmPFC), spanning ACC and dorsal PL, and the ventromedial prefrontal cortex (vmPFC), which includes the ventral PL, IL, and in some studies the dorsal peduncular cortex (DP) and dorsal tenia tecta (DTT). The DP/DTT have recently been implicated in the regulation of stress-induced sympathetic responses via projections to the hypothalamus. While many studies implicate the PL and IL in anxiety-, depression-like and fear behavior, the contribution of the DP/DTT to affective and emotional behavior remains unknown. Here, we used chemogenetics to bidirectionally modulate DP/DTT activity and examine its effects on affective behaviors, cognition and stress responses in naive male and female C57BL/6J mice. We found that acute chemogenetic activation of DP/DTT neurons caused a significant increase in anxiety-like behavior in the open field and elevated plus maze tests, as well as in passive coping in the tail suspension test. In contrast, chemogenetic inhibition of the DP/DTT had no effect on affective behavior, but facilitated auditory fear memory acquisition without affecting memory retrieval. Additionally, DP/DTT activation led to an increase in plasma corticosterone levels. These findings point to the DP/DTT as a new regulator of affective behavior in mice.