NEUROTROPHINS AND SYNAPTIC PLASTICITY

Project Details

Description

Our recent work has indicated that trophic regulation of hippocampai synaptic plasticity is a multicomponent process, modulating multiple functions in space and time. BDNF exerts acute (minutes), delayed (tens of minutes) and long term (hours to days) actions, and elicits specific effects at pre- and post-synaptic loci. Using electrophysiologic, molecular and biochemical approaches at the population and single cell levels, we have begun to define and characterize these components, and have identified at least one gene, Rab3A, underlying one component of plasticity. Since different components may differentially regulate developmental plasticity, synaptogenesis itself, synaptic refinement and memory, we now plan to define these components and underlying mechanisms in detail. We will examine the hypothesis that trophic regulation constitutes a temporospatial spectrum, governing acute plasticity leading to synaptogenesis and synaptic refinement, thereby organizing brain architecture and function. We have previously found that BDNF increases the strength of glutamatergic synapses through phosphorylation of the NR1 and NR2B subunits of postsynaptic NMDA receptors, enhancing channel open probability and delayed plasticity. Transcriptional analysis and use of knockout mutant mice revealed that the presynaptic Rab3A gene is required for acute plasticity. We will now combine population and single celt study, performing combined whole cell patch damp, transcriptional and biochemical analysis to characterize the trophic transition from synaptic strengthening to synaptogenesis.
StatusFinished
Effective start/end date10/1/889/30/07

Funding

  • National Institute of Child Health and Human Development: $86,444.00
  • National Institute of Child Health and Human Development: $145,152.00

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