<i>Grin2b</i>-mutant mice exhibit heightened remote fear via suppressed extinction and chronic amygdalar synaptic and neuronal dysfunction.

ABSTRACT: Individuals with autism spectrum disorders (ASD) frequently show long-lasting traumatic fear memory, but the underlying mechanisms remain unclear. Here, we report that Grin2b-mutant mice carrying a human ASD-risk mutation (Grin2b^C456Y/+ mice) show normal acquisition of contextual fear memory but suppressed fear memory extinction and enhanced remote fear memory responses, along with anxiety- and social-related abnormalities. After footshock and fear extinction, these mutants chronically develop occluded neuronal activation in the basal amygdala (BA) detectable at remote fear memory retrieval, which involves suppressed spontaneous excitatory synaptic transmission and neuronal excitability. Chemogenetic activation of mutant BA neurons during fear extinction improves f

SUBMITTER: Kang M 

PROVIDER: S-EPMC12442867 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature