The Actin Cytoskeleton and Synaptic Plasticity

抄録

Dendritic spines form the postsynaptic contact elements for most excitatory synapses in the central nervous system. Using time-lapse imaging of living neurons expressing proteins tagged with green fluorescent protein (GFP) we discovered that dendritic spines undergo rapid changes in shape thus identifying them as the major sites of morphological plasticity in neuronal circuits of the brain. This motility is driven by dynamic actin filaments and is differentially regulated by various subtypes of postsynaptic glutamate receptors. Activation of AMPA receptors produces an immediate blockade of spine motility which is reversed as soon as the stimulus is withdrawn. By contrast, blockade of spine motility via NMDA receptors requires 30 min to develop and persists for hours after the stimulus is withdrawn. To understand the cellular mechanisms underlying these effects we examined the influence of actin binding proteins in dendritic spines. Profilin shows activity-dependent targeting to spine heads which depends on activation of NMDA receptors and is induced by electrical stimulation patterns associated with changes in synaptic strength such as LTP. Simulataneously actin dynamics are suppressed and spine motility is blocked for several hours. Conversely, blocking profilin targeting to spines by expressing a peptide that inhibits its binding to VASP family proteins destabilizes spine morphology. Together with data for other actin binding proteins to be presented, this suggests that several distinct receptor dependent mechanisms regulate the dynamic state of the spine actin cytoskeleton and hence morphological plasticity at excitatory synapses. [J Physiol Sci. 2006;56 Suppl:S2]