A role for synaptopodin and the spine apparatus in hippocampal synaptic plasticity.

Spines are considered sites of synaptic plasticity in the brain and are capable of remodeling their shape and size. A molecule thathas been implicated in spine plasticity is the actin-associated protein synaptopodin. This article will review a series of studies aimed at elucidating the role of synaptopodin in the rodent brain. First, the developmental expression of synaptopodin mRNA and protein were studied; secondly, the subcellular localization of synaptopodin in hippocampal principal neurons was analyzed using confocal microscopy as well as electron microscopy and immunogold labelling; and, finally, the functional role of synaptopodin was investigated using a synaptopodin-deficient mouse. The results of these studies are: (1) synaptopodin expression byhippocampal principal neurons develops during the first postnatal weeks and increases in parallel with the maturation of spines in the hippocampus. (2) Synaptopodin is sorted to the spine compartment, where it is tightly associated with the spine apparatus, an enigmatic organelle believed to be involved in calcium storage or local protein synthesis. (3) Synaptopodin-deficient mice generated by gene targeting are viable but lack the spine apparatus organelle. These mice show deficitsin synaptic plasticity as well as impaired learning and memory. Taken together, these data implicate synaptopodin and the spine apparatus in the regulation of synaptic plasticity in the hippocampus. Future studies will be aimed at finding the molecular link between synaptopodin, the spine apparatus organelle, and synaptic plasticity.