Graduate Training in Neuroscience
University of Washington
Daniel R. Storm
dstorm@uw.edu
206-543-7028
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.