Brd4 participates in epigenetic regulation of the extinction of remote auditory fear memory.

Brd4 participates in epigenetic regulation of the extinction of remote auditory fear memory. Neurobiol Learn Mem. 2021 Jan 15;:107383 Authors: Huang FL, Li F, Zhang WJ, Li SJ, Yang ZH, Yang TL, Qi J, Duan Q, Li CQ Abstract BACKGROUND: Inaccurate fear memories can be maladaptive and potentially portrait a core symptomatic dimension of fear adaptive disorders such as post-traumatic stress disorder (PTSD), which is generally characterized by an intense and enduring memory for the traumatic events. Evidence exists in support of epigenetic regulation of fear behavior. Brd4, a member of the bromodomain and extra-terminal domain (BET) protein family, serves as a chromatin "reader" by binding to histones in acetylated lysine residues, and hence promotes transcriptional activities. However, less is known whether Brd4 participates in modulating cognitive activities especially memory formation and extinction. Here we provide evidence for a role of Brd4 in modulation of auditory fear memory. Auditory fear conditioning resulted in a biphasic Brd4 activation in the anterior cingulate cortex (ACC) and hippocampus of adult mice. Thus, Brd4 phosphorylation occurred 6 hours and 3-14 days, respectively, after auditory fear conditioning. Systemic inhibition of Brd4 with a BET inhibitor, JQ1, impaired the extinction of remote (i.e., 14 days after conditioning) fear memory. Further, conditional Brd4 knockout in excitatory neurons of the forebrain impaired...
Source: Neurobiology of Learning and Memory - Category: Neurology Authors: Tags: Neurobiol Learn Mem Source Type: research