Alteration of synaptic network dynamics by the intellectual disability protein PAK3

摘要: Several gene mutations linked to intellectual disability in humans code for synaptic molecules implicated small GTPase signaling. This is the case of Rac/Cdc42 effector p21-activated kinase 3 (PAK3). The mechanisms responsible defects and consequences mutation on development wiring brain networks remain unknown. Here we show that expression PAK3 mutants, suppression PAK3, or inhibition function rat hippocampal slice cultures interfere with activity-mediated spine dynamics. Inhibition resulted two main alterations: (1) an increased growth new, unstable spines, occurring clusters, mediated by activity; (2) impairment plasticity-mediated stabilization interfering formation persistent spines. Additionally, find specifically recruited activity from dendrites into providing a new mechanism through which could participate control both local growth. Together, these data identify novel regulating rearrangement connectivity associated learning suggest refinement during account disability.