Molecular mechanisms of synaptic plasticity

Abstract

Animals are able to alter their responses to specific environmental stimuli by learning and to retain those acquired behavioral changes through memory. Long-lasting changes in the stength of neuronal connections are thought to form the physical basis for learning and memory-related changes. The growth of new synapses accompanies learning in the sea slug Aplysia. We have isolated a homologue of the vertebrate neural cell adhesion molecule NCAM that is modulated with learning-related synaptic plasticity in Aplysia. The modulation of ApCAM may direct the growth of new synaptic contacts during learning. In vertebrates the precise molecular mechanisms involved in the alteration of synaptic strength are unclear. Moreover, the role that different forms of synaptic plasticity play in the behaviors generated by an intact functioning nervous system are difficult to ascertain. In order to extend the understanding of learning and memory at the molecular level into the vertebrate nervous system, we have attempted to generate transgenic mice in which long-lasting forms of synaptic plasticity are altered. These mice serve not only to link the molecule to synaptic plasticity but also to subsequent behavioral changes in the animal.