Long‐term potentiation (LTP) induces co‐localization of calmodulin and neurogranin in the dendritic spines of mouse hippocampal CA1 pyramidal neurons

Abstract

Calmodulin (CaM) and neurogranin (Ng) are abundant neuronal proteins in the forebrain and their interactions have been hypothesized to enhance the synaptic plasticity. Deletion of Ng gene in mice causes deficits in learning the hippocampus‐ and amygdala‐dependent behavioral tasks, and the high‐frequency stimulation (HFS)‐induced LTP. Immunohistochemical staining of CaM and Ng in the hippocampal slices of wild type mice revealed that both proteins were co‐localized in the soma and dendrites of the principle neurons. However, unlike the relatively even distribution of Ng in the soma and dendrites of the CA1 pyramidal neurons, CaM exhibited an asymmetrical distribution in these neurons where the somatic concentration was at least ten times greater than that in the dendrites. Surprisingly, majority of the somatic CaM was localized in the nucleus. Thus, under the basal conditions the overwhelmingly high Ng/CaM concentration ratio in the distal dendrites renders very little free CaM for the activation of CaM‐dependent enzymes. In these slices, HFS (a single train of 1 s, 100 Hz) caused mobilization of CaM from soma to associate with Ng in dendrites that lead to the expression of LTP. After HFS, CaM exhibited a patchy distribution in the apical dendrites of the stimulated CA1 region. Both CaM and Ng was found to associate with the dendritic spines adjacent to the stimulating electrode. These findings suggest that the association of CaM and Ng at the stimulated dendritic spines may enhance the synaptic efficacy by increasing the Ca2+ transients as predicted by the “mass‐action mechanism” and they may also serve as synaptic tags for the stimulated dendritic branches. (Supported by Intramural Program of NICHD, NIH).