Cdk5 modulates morphological plasticity of dendritic spines induced by Amphetamine in hippocampal pyramidal neurons

FERRERAS SOLEDAD; PISANO VICTORIA; KRAPACHER FAVIO; POZZO-MILLER LUCAS; PAGLINI GABRIELA

Huerta Grande

Congreso; First Joint Meeting of the Argentine Society for Neuroscience (SAN) and the Argentine Workshop in Neuroscience (TAN) ?(Primera Reunión Conjunta de Neurociencias IRCN); 2009

Cdk5 Modulates Morphological Plasticity of Dendritic Spines Induced by Amphetamine in Hippocampal Pyramidal Neurons Experience-dependent changes in behavior are thought to involve structural modifications in the central nervous system, especially alterations in patterns of synaptic connectivity. However, little is known about the morphological plasticity occurring during exposure to drugs of abuse. One of the targets of such structural plasticity are dendritic spines, which are dynamic, actin-rich protrusions. Recent reports have suggested that cdk5 plays an important role in drug addiction. In this study, we tested the role of cdk5 in amphetamine (Amph)-induced dendritic spine formation. Hippocampal slices maintained in organotypic tissue culture were biolistically-transfected with cDNAs coding for eYFP and exposed to different Amph doses (50 and 100µM) for 48h. Quantitative analyses of dendritic spine density and morphology were carried in CA1 and CA3 hippocampal pyramidal neurons. Our results demonstrate that Amph exposure increased spine density in apical dendrites of both regions and changed the proportion of morphological spine types. Interestingly, cdk5 inhibition by expression of a dominant negative mutant during Amph exposure, decreased spine density. These results suggest that Amph-induced spine formation require intact cdk5 activity and encourage us to propose cdk5/p35 as an excellent candidate that might mediate the regulation of actin cytoskeleton, through the phosphorylation of specific substrates that interact with actin biding proteins. PAK1 is a cdk5 substrate to test in future experiments, since it is a key protein that switch from an active to an inactive state and thereby mediate the rapid and dynamic regulation of the actin cytoskeleton, essential in dendritic spine morphogenesis.