Reactivating brain circuits reverses autism-like symptoms in mice by restoring neuron structure

A mouse model of autism with a 15q11-13 duplication showed shortened axon initial segments in prefrontal neurons, reducing excitability. Chemogenetic activation of a circuit from the medial prefrontal cortex to the dorsal raphe nucleus lengthened the AIS, normalized sodium-channel components, and markedly improved social interaction while reducing repetitive digging. The AIS changes appeared reversible, suggesting they are a flexible, circuit-level biomarker rather than permanent damage. While promising, the findings are limited to mice and one autism model, and researchers call for live-cell imaging and broader models before considering human translation.