Abstract
Dysfunctions in memory recall lead to pathological fear; a hallmark of trauma-related disorders, like posttraumatic stress disorder (PTSD). Both, heightened recall of an association between a cue and trauma, as well as impoverished recall that a previously trauma-related cue is no longer a threat, result in a debilitating fear toward the cue. Glucocorticoid-mediated action via the glucocorticoid receptor (GR) influences memory recall. This literature has primarily focused on GRs expressed in neurons or ignored cell-type specific contributions. To ask how GR action in nonneuronal cells influences memory recall, we combined auditory fear conditioning in mice and the knockout of GRs in astrocytes in the prefrontal cortex (PFC), a brain region implicated in memory recall. We found that knocking out GRs in astrocytes of the PFC disrupted memory recall. Specifically, we found that knocking out GRs in astrocytes in the PFC (AstroGRKO) after fear conditioning resulted in higher levels of freezing to the CS+ tone when compared with controls (AstroGRintact). While we did not find any differences in extinction of fear toward the CS+ between these groups, AstroGRKO female but not male mice showed impaired recall of extinction training. These results suggest that GRs in cortical astrocytes contribute to memory recall. These data demonstrate the need to examine GR action in cortical astrocytes to elucidate the basic neurobiology underlying memory recall and potential mechanisms that underlie female-specific biases in the incidence of PTSD.
Highlights
Among many mechanisms, glucocorticoid action via signaling through glucocorticoid receptors (GRs) is an important neurobiological pathway that underlies the recall of salient information
While nr3c1 tranfect—P > 0.05, GR status main effect—F(1,33) = 13.30, P = 0.0009; data collapsed across sexes)
We combined the robust and reliable experimental framework provided by auditory fear conditioning with molecular genetic-based knockout of GRs in cortical astrocytes to ask whether and how GRs in astrocytes in the prefrontal cortex (PFC) impact learning and memory
Summary
Glucocorticoid action via signaling through glucocorticoid receptors (GRs) is an important neurobiological pathway that underlies the recall of salient information. The relationship between glucocorticoids, GRs, learning and memory is complicated and within the literature cited above, one can find examples of GR action being facilitatory as well as inhibitory to learning and memory recall. As expansive as this research is, the influence of GRs on learning, memory, and recall of learning has mostly focused only on GR action in neurons or has ignored cell type specific contributions. While glia are approximately as common as neurons in the nervous system (von Bartheld et al 2016; von Bartheld 2018), the role of GRs in glial cells on the recall of salient environmental cues has been neglected. C (PFC), a brain region critical for the recall of memory
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