Monday, January 01, 1990


Nature Reviews Neuroscience - Reviews: "Much evidence indicates that, after learning, memories are created by alterations in glutamate-dependent excitatory synaptic transmission. These modifications are then actively stabilized, over hours or days, by structural changes at postsynaptic sites on dendritic spines. The mechanisms of this structural plasticity are poorly understood, but recent findings are beginning to provide clues. The changes in synaptic transmission are initiated by elevations in intracellular calcium and consequent activation of second messenger signalling pathways in the postsynaptic neuron. These pathways involve intracellular kinases and GTPases, downstream from glutamate receptors, that regulate and coordinate both cytoskeletal and adhesion remodelling, leading to new synaptic connections. Rapid changes in cytoskeletal and adhesion molecules after learning contribute to short-term plasticity and memory, whereas later changes, which depend on de novo protein synthesis as well as the early modifications, seem to be required for the persistence of long-term memory.

Much evidence indicates that the formation of long-term memory involves enduring alteration of synaptic responses to the learned stimulus. These changes subserve memory storage and ensure its retrieval. A central question derived from these observations is, what are the cellular and molecular events that lead to such changes?
Recent findings show that behavioural learning or the artificial form of synaptic plasticity known as long-term potentiation (LTP) results in morphological changes in excitatory synapses at dendritic spines. Changes in spine morphology could alter postsynaptic responses to extracellular stimulation, such as changes in calcium influx and calcium storage, changes in synaptic transmission, and induction of local protein synthesis. These cellular events are postulated to contribute to changes in synaptic efficacy underlying learning.
The architecture of spines, and therefore their ability to change shape, depends on the specialized underlying structure of the cytoskeletal filaments. Studies have shown that LTP induces alterations in actin polymerization in spines. Moreover, inhibition of actin polymerization suppresses LTP.
Activation of glutamate receptors in the spine induces actin-dependent modulation of spine morphology. Glutamate contributes to the initial actin-dependent spine motility and also to events that lead to spine stability. Evidence indicates that AMPA (-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors contribute to actin-dependent spine stabilization. Increases in AMPA receptors at the synapse (observed after stimulation that leads to long-term plasticity) could contribute to the stabilization of spine morphology.
Rho GTPases mediate actin cytoskeleton-dependent neuronal morphogenesis and might be activated by glutamate and adhesion molecules. Recent findings have shown a central role for the Rho GTPase pathway in memory formation and synaptic plasticity.
Adhesion molecules also modulate spine morphology by regulating actin cytoskeleton. Such molecules have been shown to be involved in long-term memory and LTP formation.
Together, these observations indicate a model in which glutamate transmission and adhesion molecules regulate neuronal morphogenesis initiated by stimulation that leads to LTP and long-term memory. These structural changes are mediated and stabilized by the Rho GTPases and the actin cytoskeleton. Alterations in synaptic morphology and stabilization of these changes are hypothesized to be involved in memory consolidation and persistence."

Raphael Lamprecht & Joseph LeDoux
Nature Reviews Neuroscience 5, 45-54 (2004); doi:10.1038/nrn1301
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