Premachandran, H. | Search bioRxiv

bioRxiv2025

C57BL/6 Mouse Substrain Differences in the Ontogeny of Auditory Fear

Early life adversity is a major risk factor for mental disorders later in life. Critically, genetic and individual differences modulate the impact of early life trauma and stress on adult mental health, emphasizing the importance of understanding how the early onset of individual differences may shape behavioral outcomes across life. In rodents, genetic differences can be studied using inbred rodent strains or substrains. While C57BL/6 mouse substrains differ in their adult fear behavior, it is unclear when in development these differences emerge. Here we compared the ontogenesis of remote auditory fear retrieval, spontaneous recovery and renewal in the mouse C57BL/6J (Jax, from Jackson Laboratories) and C57BL/6NTac (Taconic Biosciences) substrains spanning postnatal days (P)16, P18, P21, P25 and P30. Taconic male and female mice show an earlier onset of persistent auditory fear memory and spontaneous recovery (females only) compared to Jax mice. Male Taconic mice also display earlier onset of renewal compared to Jax males. These data identify ontogenetic differences in fear processing among C57BL/6 mouse substrains, highlighting how individual differences can contribute to altered behavioral phenotypes in early development.

neuroscience↗

bioRxiv2023

Dorsal peduncular cortex activity modulates affective behaviors in mice

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.

neuroscience↗