Cellular and molecular basis of synaptic strength regulation

Abstract

Synapses mediate information transmission in the nervous system, and dynamic changes in the efficacy of synaptic transmission or synaptic strength, play a fundamental role in cognitive functions including emotion, computation, perception and learning and memory. Our research seeks to understand how individual synapses acquire a particular strength, and how the strength of individual synapses is dynamically modified by network activity and in relationship to other synapses sharing the network. To address these questions experimentally, we combine methods of molecular biology, cell biology, biochemistry, electrophysiology, fluorescence liveimaging, and electron microscopy. In order to unravel the molecular mechanisms that underlie these processes, we have focused our attention on coordinate regulation of synapse structure and function. Towards this end, we used a novel photoconductive stimulation technique that illustrated the coordination remodeling of pre and postsynaptic cytoskeleton during synaptic plasticity (Colicos et al., 2001). This motivated us to examine how synapse adhesion proteins that couple the pre and the postsynaptic terminals directly or via the extracellular matrix and glial cells contribute to synaptic strength regulation. In this lecture I will highlight the roles for integrins and N-cadherin/β-catenin complex that we have identified in controlling glutamate receptors and homeostatic forms of synaptic plasticity (Okuda et al., 2007; Cingolani et al., 2008; Vitureira et al., 2011; Pozo et al., 2012; McGeachie et al., 2012). Reference