Our findings show that a chemogenetic manipulation which augments the PV-IN inhibitory input onto CA1 PN in Ambra1+/− females rescues their autistic-like behavioral and dendritic spines alterations and concurrently normalizes their decreased levels of hippocampal estrogen receptors, the latter observation providing the first evidence that variations in hippocampal neural activity locally modulate expression of these receptors in a model of female autism. This evidence concerns the gene ESR1 and autism.