Multiple Levels of Synaptic Regulation by NMDA-type Glutamate Receptor in Normal and Disease States

摘要

The acquisition of new behaviors and the formation of memories occur through the creation and regulation of synaptic contacts within the brain. In mammals, most synapses form onto small, bulbous cellular compartments called dendritic spines (reviewed in Harris 1999). Spines are dynamic structures that appear rapidly following activity patterns that lead to memory formation, and these fast structural alterations are believed to contribute to the remarkable plasticity of the brain (Engert and Bonhoeffer 1999; Maletic-Savatic et al. 1999; Toni et al. 1999). Each spine is biochemically isolated (Sabatini et al. 2002} and contains components of many signaling pathways necessary for synaptic plasticity (Kornau et al. 1995). Here we describe recent work in our laboratory focusing on the role of NMDA-type glutamate receptors (NMDAR) in regulating the function and plasticity of dendritic spines and synapses in both normal and disease states (Alvarez et al.2007; Ngo-Anh et al. 2005; Bloodgood and Sabatini 2007a; Shankar et al. 2007).