-mutant mice exhibit heightened remote fear via suppressed extinction and chronic amygdalar synaptic and neuronal dysfunction.

Scientists studied mice with an autism-related genetic change and found they had trouble 'unlearning' fears, leading to stronger long-lasting fear memories. The research showed problems in a brain area called the amygdala that processes emotions. When researchers stimulated this brain area, the mice got better at overcoming their fears, suggesting this could be important for understanding why some autistic people have lasting trauma responses.

This preclinical study examined fear memory processing in mice carrying a human ASD-risk mutation. The mutant mice showed normal initial fear learning but impaired fear extinction (ability to unlearn fear) and enhanced long-term fear responses. Researchers found chronic dysfunction in basal amygdala neurons, including suppressed excitatory synaptic transmission and reduced neuronal activity. When scientists artificially activated these neurons during fear extinction training, the mice showed improved fear extinction and reduced remote fear responses, along with normalized brain function.

These findings suggest that impaired fear extinction in ASD may involve specific amygdala dysfunction that maintains traumatic fear memories over time.

Suggests fear extinction deficits in autism may involve specific amygdala dysfunction that could be therapeutically targeted. May inform development of interventions for trauma-related symptoms in autism, though human validation is needed.

Single preclinical mouse study with unknown sample size. Findings require validation in human studies. Genetic mutation specificity and generalizability to broader ASD population unclear from abstract.

Individuals with autism spectrum disorders (ASD) frequently show long-lasting traumatic fear memory, but the underlying mechanisms remain unclear. Here, we report that-mutant mice carrying a human ASD-risk mutation (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 fear memory extinction and remote fear memory responses without affecting anxiety- or social-related phenotypes.

This rescue involves normalized spontaneous excitatory synaptic transmission and neuronal excitability. These results suggest thatmice, through impaired fear memory extinction, chronically develop suppressed spontaneous excitatory synaptic transmission and neuronal excitability in BA neurons that enhances remote fear memory responses.