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 naïve 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.

The mouse dorsal peduncular cortex encodes fear memory

“…While our findings have provided numerous lines of evidence suggesting the DP plays a role in fear memory encoding and retrieval but not extinction, a recent study by Botterill and colleagues reported that the DP/DTT seems play a role in fear extinction rather than fear encoding and retrieval 9 . These differences may relate to which specific DP outputs were manipulated, the method of manipulation, and anatomical differences in viral targeting.…”

“…Therefore, due to its anatomical location ventral to IL, some have hypothesized that DP also functions to suppress fear 8 . Despite this, the role that DP might play in fear suppression or some other aspect of memory has largely not been tested (but see recent study 9 ).…”

The mouse dorsal peduncular cortex encodes fear memory

“…While our findings have provided numerous lines of evidence suggesting that the DP plays a role in fear memory encoding and retrieval but not extinction, a recent study by Botterill and colleagues reported that the DP/DTT seems play a role in fear extinction rather than fear encoding and retrieval. 9 These differences may relate to which specific DP outputs were manipulated, the method of manipulation, and anatomical differences in viral targeting. Moreover, an additional study revealed sexual dimorphic activity profiles in the DP following auditory fear conditioning, where female mice exhibited significantly higher levels of conditioning-induced cFos expression compared to males.…”

“…Therefore, due to its anatomical location ventral to the IL, some have hypothesized that the DP also functions to suppress fear. 8 Despite this, the role that the DP might play in fear suppression or some other aspect of memory has largely not been tested (but see the recent study by Botterill et al 9 ).…”

“…Following social defeat stress, the DP, along with the region immediately ventral, the dorsal tenia tecta (DTT), have been implicated in driving physiological sympathetic responses, including thermoregulation and cardiac responses. 10 – 12 Moreover, recent studies have also implicated the DP/DTT in driving anxiety-like behaviors 9 and circuits of fight or flight. 13 Given the central role for autonomic responses in fear, we hypothesized that the DP may be playing a role in fear memory processes rather than in extinction.…”