Evidence of impaired neuronal plasticity in response to inactivation of the small GTPase Rac1

Abstract

The formation and maintenance of dendrites and dendritic spines are very critical for synaptic development and plasticity, and require a very dynamic actin cytoskeleton. Rac1, a Rho GTPase largely known for its involvement in the actin cytoskeleton remodeling, is also associated with neuronal development. Our laboratory and others have recently revealed that Rac1 might have a role in plasticity, bringing us to hypothesize that Rac1 is involved in the morphological changes observed at neuronal synapses during hippocampal learning and memory as well as long‐term plasticity. To investigate our hypothesis, we used the Cre/Lox‐P system to develop a tissue‐specific mutant mouse in which Rac1 was ablated from the hippocampal area CA1. We then demonstrated that Rac1 is necessary for normal dendritic morphology and long‐term synaptic plasticity. We further showed that Rac1 is also critical for hippocampus‐dependent learning and memory tasks. Thus, regulation of Rac1 may provide a functional link between deficient neuronal morphology, aberrant synaptic plasticity and cognition impairment, phenotypes often associated with certain autistic disorders.