Abstract
Actin cytoskeletal organization in dendrites and dendritic spines are believed to form a molecular basis for the morphological plasticity at brain synapses. We here demonstrate that actin cytoskeleton of hippocampal neurons is rapidly rearranged by N-methyl-D-aspartate (NMDA) receptor activation in both neuronal phenotype and developmental activity-dependent manner. In rat hippocampus primary cultures, a certain population (20-30%) of neurons showed drastic redistribution of its dendritic filamentous (F-) actin after a stressful NMDA stimulation (50μM for 30 s). The NMDA-induced actin rearrangement correlated with changes of spine morphology and disruption of several postsynaptic components like Homer1b/c, GluR1 and NMDAR2A, even though the synaptic contacts seemed to stay preserved. Immunohistochemical characterization showed that NMDA-susceptible cells did not express calbindin-D28k. Reduction of network activity by chronic tetrodotoxin application resulted in an increased number of calbindin-D28k -negative and NMDA susceptible cells. Exogeneous calbindin expression in these neurons could recover their resistance to NMDA induced F-actin redistribution. These data indicate that F-actin organization is diverse among different populations of neurons, which are selectively sensitive to hyper excitatory input. Such neuronal type-specific heterogeneity also points toward specific molecular mechanisms that contribute to cytoskeletal regulation in dendrites. [J Physiol Sci. 2006;56 Suppl:S30]
