ANATOMICAL AND FUNCTIONAL MICRODOMAINS OF CALCIUM AND CALCIUM-DEPENDENT PROTEINS IN DENDRITIC SPINES
Intracellular Ca2+ concentration is central in regulating synaptic efficacy, but it also has many other effects. The focus of this study is on dendritic spines, which act as specialized compartments for calcium signals. To augment imaging methods that lack the spatiotemporal resolution to explore this compartmentalization, we have combined immunocytochemical data with biophysical modeling. High-resolution immunogold studies reveal that both ligand-gated NMDA receptors and L-type voltage-gated calcium channels concentrate at the synapse in neocortex and hippocampus. In addition, several calcium-binding proteins concentrate at the PSD, as may the phosphatases PP1 and PP2B. Monte Carlo simulations of Ca2+ dynamics following different types of neuronal activity result in different Ca2+ distributions within the spine, and consequently to differential activation of calcium-dependent proteins. Both CaMKII and PP2B, implicated in the induction of LTP and LTD, respectively, are activated by calmodulin (CaM). When action potentials and EPSPs are paired to induce