Dendritic spines form the postsynaptic point of contact for most excitatory synapses. It is known that long-term changes in synaptic efficacy are accompanied by stabilization of spine morphology, but it is unclear exactly how synaptic activity influences spine stability. Reporting in Nature Neuroscience, Ackermann and Matus now propose a mechanism that relies on activity-dependent targeting of a cytoskeletal regulator to spines.
Profilin is a protein that regulates the polymerization of the main cytoskeletal element actin. Ackermann and Matus examined the distribution of profilin in relation to synaptic activity and spine motility. First, they treated hippocampal neurons in culture with glutamate, which activates postsynaptic N-methyl-D-aspartate (NMDA) receptors. They found that this led to an accumulation of profilin in the dendritic spines, which was blocked if the cells were treated with NMDA receptor antagonists.
The authors showed that electrical stimulation of the neurons could also cause profilin to be targeted to spines. However, only certain patterns of electrical activity were effective, and interestingly, they were the same patterns that elicit long-term alterations in synaptic efficacy.
Ackermann and Matus also showed that the stabilization of spines depended on the redistribution of profilin. They prevented profilin from accumulating in spines by transfecting neurons with a construct that encoded a cytoplasmic profilin-binding peptide. The dendritic spines on the transfected cells remained in an irregular elongated conformation instead of undergoing maturation and adopting a compact mushroom shape.
These findings indicate a model for spine stabilization, in which synaptic activity causes profilin to be targeted to spines, which in turn promotes actin polymerization. Although profilin and actin do not seem to control synaptic efficacy directly, Ackermann and Matus suggest that they might tag synapses that are destined to undergo long-term changes, thereby providing an important intermediate step in the process of memory consolidation.
ORIGINAL RESEARCH PAPER
Ackermann, M. & Matus, A. Activity-induced targeting of profilin and stabilization of dendritic spine morphology. Nature Neurosci. 6, 1194–1200 (2003)
Ottersen, O. P. & Helm, P. J. How hardwired is the brain? Nature 420, 751–752 (2002)
Martin, K. C. & Kosik, K. S. Synaptic tagging — who's it? Nature Rev. Neurosci. 3, 813–820 (2002)
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Wood, H. How activity shapes spines. Nat Rev Neurosci 4, 937 (2003). https://doi.org/10.1038/nrn1279