Grant: $14,644 - National Institutes of Health - Jul. 21, 2009
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Award Description: 5R01NS040593-09; P.I. Lucas Pozzo-Miller, PhD; SPIN student Meredith Lane This grant is focused on the immediate actions of the neurotrophin BDNF on membrane currents and intracellular Ca2+ levels in hippocampal neurons. BDNF has recently emerged as a potent modulator of activity-dependent synaptic development and plasticity in the CNS. Dysfunctions in BDNF trafficking and release, as well as in intracellular signaling through its receptor TrkB, have been implicated in the etiology of numerous developmental and neurodegenerative brain disorders. The specific hypothesis to be tested is that BDNF triggers TrkB-dependent PLC¿ activation followed by Ca2+ mobilization from IP3-sensitive stores in CA1 pyramidal neurons, leading to the activation of a sustained inward current and Ca2+ elevations mediated by TRPC channels. We expect the proposed studies to provide a comprehensive understating of the immediate actions of BDNF on neuronal membrane currents and Ca2+ homeostasis, leading to enduring changes in synaptic function, structure, and plasticity. An administrative supplement to extend these studies will examine the mechanisms of activity-dependent BDNF release from hippocampal presynaptic terminals using a newly developed optical fluorescence probe. A cDNA expression plasmid encoding mature BDNF fused with pH-sensitive super ecliptic GFP (pHluorin) has already been tested in hippocampal neurons in primary culture. In addition, this BDNF-pHluorin construct has been packaged into a lentivirus, which will allow targeted transfection of selected neuronal populations in organotypic slice cultures or in vivo for subsequent multiphoton excitation imaging of BDNF release in slices. These studies are a straightforward extension of Aim 3 of the parent grant, where activity-dependent BDNF release is assessed by the activation of postsynaptic TRPC currents. We will use research infrastructure already in place in the Pozzo-Miller lab and imaging cores at UAB including the Alabama Neuroscience Blueprint Center (funded by NINDS). For the next two summers, we will employ 1 or 2 undergraduates to work alongside the PI and a postdoctoral associate to perform the neuronal transfections, imaging experiments, and quantitative analyses.
Project Description: Same as Above
Jobs Summary: Summer Student (Total jobs reported: 1)
Project Status: Less Than 50% Completed
This award's data was last updated on Jul. 21, 2009. Help expand these official descriptions using the wiki below.