The majority of excitatory synapses in the brain are found on small dendritic protrusions called spines. Although the primary postsynaptic component of a synapse, the postsynaptic density (PSD), can only be resolved at the electron microscopic level, recent studies at the light microscopic level have shown that dendritic spines are extremely dynamic, capable of changing their shape and disappearing or emerging de novo from dendritic shafts. Despite the potential limitation of electron microscopic studies providing only a snapshot of the brain at a single time point, several groups have provided evidence of learning-related synaptic plasticity that corresponds well to what is known about cytoskeletal changes among dendritic spines. An emerging view from these electron microscopic studies is that learning involves the formation of new axospinous synapses and a remodeling of existing ones that includes alterations in their size, and perhaps strength. The application of modern methodologies to electron microscopy, such as unbiased stereological sampling and postembedding immunogold localization of synaptic proteins, will continue to elaborate our understanding of synaptic plasticity associated with learning, while also complementing research conducted at the electrophysiological and light microscopic levels.

tDepartment of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 USA; [email protected]

'Department of Cell and Molecular Biology, Feinberg School of Medicine and Institute for Neuroscience, Northwestern University, Chicago, IL 60611 USA; [email protected]

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