Graduate Training in Neuroscience
University of Washington
Daniel R. Storm
Professor, Department of Pharmacology
Our lab is interested in molecular mechanisms underlying neuroplasticity. Recent evidence from our lab and others suggests that the cAMP, Ca2+, and MAP kinase signal transduction pathways may contribute to various forms of neuroplasticity. In fact, cross-talk between these regulatory pathways may be particularly important for some forms of synaptic plasticity.
Learning and memory have two functionally and mechanistically distinct components: a short-term phase that lasts no more than several hours, and a long-term component that can continue for days or longer. The formation of long-term memory requires transcription of specific genes. Another property of long-term memory is a dependency on the cAMP, Ca2+, and MAP kinase signal transduction systems. LTP is an activity dependent strengthening of synaptic efficacy which may be a useful model for studying learning-induced changes in synaptic efficacy. Like learning and memory, LTP has decremental (D-LTP: 1-3 hours) and long-lasting forms (L-LTP: >3 hours). L-LTP is sensitive to inhibitors of transcription and translation. A key event in the generation of L-LTP is activation of glutamate receptors and/or voltage-sensitive calcium channels with increases in intracellular free Ca2+. This triggers a series of events required for long-term changes at the synapse including the activation of Ca2+ stimulated adenylyl cyclases. Our recent data using transgenic mouse model systems indicates that L-LTP may depend on cAMP-mediated transcription and maximal expression of CRE-mediated transcription in neurons may depend on coactivation of the Ca2+, cAMP, and MAPK signaling systems.