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Glutamate sensitivities of single dendritic spines were investigated with a two-photon photolysis of a caged-glutamate compound and the patch-clamp method in mouse hippocampal slice preparations. We found that the fast glutamate responses mediated by AMPA receptors were proportional to the volume of the spine head, but the slow responses induced by NMDA receptors displayed only weak correlation with the spine head volume and were independently regulated with the expression of AMPA receptors. This indicates that the strength of synaptic connection is stored as the spine structures, but that its plasticity may be regulated by independent factors. Abnormalities in spine shapes and distributions are commonly detected in most brain dysfunctions, including metal retardations, where structural consolidation phase may be impaired. These observations suggest that a physical basis of the memory in the cerebral cortex resides in the alteration and maintenance of spine structures.
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