Effects of sex and retention interval on the retrieval and extinction of auditory fear conditioning

Abstract

Fear memory retrieval is relevant to psychiatric disorders such as post-traumatic stress disorder (PTSD). One of the hallmark symptoms of PTSD is the repeated retrieval and re-experiencing of the initial fear memory even long after the traumatic event has occurred. Women are nearly twice as likely to develop PTSD following a trauma than men, thus sex differences in the retrieval of fear memories is highly relevant for understanding the development and maintenance of PTSD. In the current study, we aimed to examine sex differences in the retrieval and extinction of either recent or remote fear memories. To do so, we conditioned male and female rats either 1 day (recent) or 28 days (remote) prior to testing retrieval and extinction. While there was no effect of sex or retention interval on initial retrieval, we found that remotely conditioned females exhibited higher rates of freezing than remotely conditioned males in later retrieval/extinction sessions, suggesting a sex difference in the retrieval and/or extinction of remote, but not recent, fear memories. Overall, these results are the first to demonstrate a sex difference in the extinction of remote fear memory, and this may contribute to the differential expression of fear-related disorders like PTSD in men and women.

Renewal of conditioned fear in male and female rats.

“…However, recent research has shown that darting is an unconditioned response (e.g., nonassociative; Trott et al, 2022). While we have previously failed to observe meaningful levels of darting in either male or female rats (Schoenberg et al, 2022), the current series of studies utilized different conditioning parameters than our previous work. Thus, the same video recordings used to score freezing were used to score instances of darting during each CS presentation during the renewal test sessions.…”

“…Automated scoring of freezing was conducted as described by Schoenberg et al (2022). Video streams were acquired in near-infrared (720 P resolution, 29.97 frames per second) by Anpviz IPCameras (model IPC-B850W) mounted in each chamber.…”

“…Automated scoring of freezing was conducted as described by Schoenberg et al (2022). Video streams were acquired in nearinfrared (720 P resolution, 29.97 frames per second) by Anpviz This document is copyrighted by the American Psychological Association or one of its allied publishers.…”

The sexually divergent cFos activation map of fear extinction

“…Previous studies have reported sex differences in rodents in the fear memory task [ [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] ]. For instance, in context fear conditioning, the freezing level of male rats was significantly higher than that of females, whether the stage was acquisition or extinction [ [42] , [43] , [44] , [45] ].…”

Blockade of D-serine signaling and adult hippocampal neurogenesis attenuates remote contextual fear memory following multiple memory retrievals in male mice

“…Pavlovian fear conditioning is a useful tool for studying the neurobiology of normal and pathological fear ( Johnson et al, 2012 ; LeDoux, 2014 ; Bowers and Ressler, 2015 ). Contextual fear conditioning is a paradigm capable of creating fear memory to context and retrieving of the conditioned fear memory is hypothesized to share common or similar mechanisms with the re-experiencing symptoms in post-traumatic stress disorder (PTSD) ( Bowers and Ressler, 2015 ; Chaaya et al, 2018 ; Schoenberg et al, 2022 ). Retrieval of the consolidated fear memory induces two opposing processes, reconsolidation and extinction.…”