Formation of False Context Fear Memory Is Regulated by Hypothalamic Corticotropin-Releasing Factor in Mice

Abstract

Traumatic events frequently produce false fear memories. We investigated the effect of hypothalamic corticotropin-releasing factor (CRF) knockdown (Hy-Crf-KD) or overexpression (Hy-CRF-OE) on contextual fear memory, as fear stress-released CRF and hypothalamic–pituitary–adrenal axis activation affects the memory system. Mice were placed in a chamber with an electric footshock as a conditioning stimulus (CS) in Context A, then exposed to a novel chamber without CS, as Context B, at 3 h (B-3h) or 24 h (B-24h). The freezing response in B-3h was intensified in the experimental mice, compared to control mice not exposed to CS, indicating that a false fear memory was formed at 3 h. The within-group freezing level at B-24h was higher than that at B-3h, indicating that false context fear memory was enhanced at B-24h. The difference in freezing levels between B-3h and B-24h in Hy-Crf-KD mice was larger than that of controls. In Hy-CRF-OE mice, the freezing level at B-3h was higher than that of control and Hy-Crf-KD mice, while the freezing level in B-24h was similar to that in B-3h. Locomotor activity before CS and freezing level during CS were similar among the groups. Therefore, we hypothesized that Hy-Crf-KD potentiates the induction of false context fear memory, while Hy-CRF-OE enhances the onset of false fear memory formation.

Histological Analysis of a Mouse Model of the 22q11.2 Microdeletion Syndrome

“…We substituted the region from the U6 promoter until human growth hormone polyadenylation signal (hGH polyA signal) to the synthesized DNA fragment (Biomatik, ON, Canada) which contained U6 promoter, human synapsin I promoter with EGFP, WPRE, and hGH polyA signal. AAV production was performed in accordance with the previous report [23], which is a minor modification of the protocols reported by Challis et al [24]. HEK293FT cells were passaged and cultured in 10-15 cm diameter dishes in DMEM supplemented with 10% FBS, penicillin, and streptomycin.…”