Electrically coupled but chemically isolated synapses: dendritic spines and calcium in a rule for synaptic modification.
An influential model of learning assumes synaptic enhancement occurs when there is pre- and post-synaptic conjunction of neuronal activity, as proposed by Hebb (1949) and studied in the form of long-term potentiation (LTP). There is evidence that LTP has a post-synaptic locus of control and is triggered by an elevation of intracellular calcium ion concentration, [Ca2+]i. Since synapses which undergo LTP are usually situated on dendritic spines, three effects of spine morphology on this system should be considered: (i) synapses on spines are chemically isolated by the barrier to Ca2+ diffusion due to the spine neck dimensions; (ii) the resistance of the spine neck permits a given synaptic current to bring about greater depolarization (of the spine head membrane) than the same current into a dendrite; while (iii) the spine neck resistance does not significantly attenuate current flow (in the dendrite to spine direction) because of the relatively high impedance of the spine head, and this permits electrical coupling via the dendritic tree. The specificity of LTP to activated synapses on depolarized cells has recently been attributed to special properties of the receptor-linked channel specifically activated by N-methyl-D-aspartate (NMDA). This admits calcium and other ions only when there is both depolarization and receptor activation. However, consideration of point (ii) suggests that, for spines with high resistance necks, the current through a synapse on the spine head will cause sufficient depolarization to unblock the NMDA channel. Thus, the properties of the NMDA channel do not account for the requirement for conjunction of pre- and post-synaptic activity, if these channels are located on the spine head. This suggests that additional mechanisms are required to explain why it is necessary to depolarize the post-synaptic cell in order to induce LTP. As an alternative, it is postulated that there exist voltage-sensitive calcium channels (VSCCs) on the spine head membrane, of a type which require greater membrane depolarization for activation. To generate the greater depolarization required, both pre- and post-synaptic activation would be necessary. If so, the role of dendritic or somatically located NMDA channels may be to "prime" neurons for LTP by enchancing voltage-dependent responses. A corollary is that spine resistance may regulate the threshold number of synapses required to produce LTP. It is predicted that, on spines with very high neck resistance (say, greater than 600 M omega), synaptic current alone may produce sufficient depolarization to activate VSCCs.(ABSTRACT TRUNCATED AT 400 WORDS)
Wickens
J
J
Department of Anatomy, University of Otago, Dunedin, New Zealand.
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D003712:Dendrites / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009431:Neural Conduction; D013569:Synapses / Q000502:physiology*
D015220:Calcium Channels