The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines.

摘要: Copy number variation (CNV) at the 15q11.2 region has been identified as a significant risk locus for neurological and neuropsychiatric conditions such schizophrenia (SCZ) autism spectrum disorder (ASD). However, individual roles genes this in nervous system development, function connectivity remain poorly understood. Haploinsufficiency of one gene region, Cyfip1, may provide model CNV-associated phenotypes. Here we show that altering CYFIP1 expression levels neurons both vitro vivo influences dendritic complexity, spine morphology, actin dynamics synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor lateral diffusion. is highly enriched synapses its overexpression leads to increased complexity. Neurons derived from Cyfip1 heterozygous animals on other hand, possess reduced mobile F-actin enhanced GluA2-containing AMPA mobility synapses. Interestingly, or haploinsufficiency immature number, whereas activity-dependent changes volume were occluded haploinsufficient neurons. In vivo, exhibited deficits complexity well an altered ratio immature-to-mature spines hippocampal CA1 summary, evidence dysregulation pathological CNS maturation neuronal connectivity, which contribute development symptoms seen ASD SCZ.