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Dorsal peduncular cortex activity modulates affective behavior and fear extinction in mice
Justin J Botterill1,2, Abdessattar Khlaifia1, Ryan Appings1
1Department of Psychology, University of Toronto Scarborough, Toronto, ON, M1C1A4, Canada.
Abstract:
The medial prefrontal cortex (mPFC) is critical to 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 specialized contributions from its subdivisions. The rodent mPFC is divided into the dorsomedial prefrontal cortex (dmPFC), spanning the anterior cingulate cortex (ACC) and dorsal prelimbic cortex (PL), and the ventromedial prefrontal cortex (vmPFC), which includes the ventral PL, infralimbic cortex (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 and optogenetics to bidirectionally modulate DP/DTT activity and examine its effects on affective behaviors, fear and stress responses in C57BL/6J mice. Acute chemogenetic activation of DP/DTT significantly increased anxiety-like behavior in the open field and elevated plus maze tests, as well as passive coping in the tail suspension test. DP/DTT activation also led to an increase in serum corticosterone levels and facilitated auditory fear extinction learning and retrieval. Activation of DP/DTT projections to the dorsomedial hypothalamus (DMH) acutely decreased freezing at baseline and during extinction learning, but did not alter affective behavior. These findings point to the DP/DTT as a new regulator of affective behavior and fear extinction in mice.
Insights
The dorsal peduncular cortex/dorsal tenia tecta (DP/DTT) in mice regulate anxiety-like behaviors and fear extinction. Activating these brain regions increases anxiety and improves fear extinction learning, revealing a novel role in emotional processing.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Psychiatry
Background:
- The medial prefrontal cortex (mPFC) is crucial for cognitive and emotional functions and implicated in neuropsychiatric disorders.
- Subdivisions of the rodent mPFC, including the dorsal peduncular cortex (DP) and dorsal tenia tecta (DTT), have distinct roles in behavior, but DP/DTT functions remain largely unknown.
- While the prelimbic (PL) and infralimbic (IL) cortices are linked to anxiety and fear, the DP/DTT's contribution to affective behaviors is unexplored.
Purpose of the Study:
- To investigate the role of the dorsal peduncular cortex (DP) and dorsal tenia tecta (DTT) in regulating affective behaviors, fear, and stress responses.
- To elucidate the specific contributions of DP/DTT activity to anxiety-like behavior, depression-like behavior, and fear extinction.
- To examine the impact of DP/DTT modulation on physiological stress markers like corticosterone levels.
Main Methods:
- Utilized chemogenetics and optogenetics for bidirectional modulation of DP/DTT activity in C57BL/6J mice.
- Assessed anxiety-like behaviors using the open field test and elevated plus maze.
- Evaluated depression-like behavior via the tail suspension test and fear extinction learning through auditory fear conditioning paradigms.
Main Results:
- Acute chemogenetic activation of DP/DTT significantly increased anxiety-like behaviors and passive coping.
- DP/DTT activation elevated serum corticosterone levels and enhanced auditory fear extinction learning and retrieval.
- Targeted activation of DP/DTT projections to the dorsomedial hypothalamus (DMH) reduced freezing behavior but did not affect overall affective behavior.
Conclusions:
- The dorsal peduncular cortex (DP) and dorsal tenia tecta (DTT) are identified as novel regulators of affective behavior and fear extinction in mice.
- Modulation of DP/DTT activity influences anxiety, stress responses, and the learning and retrieval of fear extinction.
- These findings highlight the DP/DTT as a potential therapeutic target for mood, fear, and anxiety disorders.
