Neuroscience 2005 Abstract
| Presentation Number: | 159.1 |
|---|---|
| Abstract Title: | Genetic and pharmacological disruption of PKA anchoring impairs some PKA-dependent forms of hippocampal LTP. |
| Authors: |
Huang, T. T.*1
; McDonough, C. B.1
; Nie, T.2
; Abel, T.1,2
1Neuroscience, Univ. of Pennsylvania, Philadelphia, PA 2Biology, Univ. of Pennsylvania, Philadelphia, PA |
| Primary Theme and Topics |
Neural Excitability, Synapses, and Glia: Cellular Mechanisms - Synaptic Plasticity -- LTP: Kinases and intracellular signaling |
| Secondary Theme and Topics | Neural Excitability, Synapses, and Glia: Cellular Mechanisms<br />- Synaptic Plasticity<br />-- LTP: Physiology and behavior |
| Session: |
159. LTP Signaling: PKA and ERK Poster |
| Presentation Time: | Sunday, November 13, 2005 8:00 AM-9:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # K5 |
| Keywords: | PROTEIN KINASE A, AKAP, LTP, LTD |
Synaptic plasticity, the activity-dependent change in the strength of neuronal connections, is a proposed cellular mechanism of memory storage that requires protein kinases such as cAMP-dependent protein kinase (PKA). Spatial compartmentalization of PKA via binding to A-Kinase Anchoring Proteins (AKAPs) is thought to contribute to the specificity of the PKA signaling pathway in effecting downstream events. Because the regulation of specificity is crucial to signal transduction pathways, we tested the hypothesis that mislocalizing PKA by Ht31, an inhibitor of PKA anchoring, would alter PKA-dependent behavioral and physiological processes. Mice that inducibly express Ht31 in forebrain neurons display alterations in hippocampal function as assessed by impairments in the spatial version of the Morris Water maze for example (Nie and Abel, SFN 2002, 2003). Expression of Ht31 also disrupts certain AKAP complexes that contain PKA and impairs a PKA-dependent form of hippocampal L-LTP (McDonough et al., SFN 2004). Here we demonstrate that some PKA-dependent forms of hippocampal L-LTP are impaired in two different lines of mice expressing Ht31 and that suppression of Ht31 expression by treatment with doxycycline (200 mg/kg) reverses these impairments. Interestingly, long-term depression (LTD) is normal in these transgenic mice as well as synaptic potentiation induced by treatment with the adenylyl cyclase agonist forskolin. PKA-dependent forms of hippocampal L-LTP are also impaired in wild type mouse hippocampal slices treated with a membrane permeable Ht31 peptide. The impairments seen are dose-dependent (1-10 µM). In contrast with intracellular delivery of Ht31 peptide, extracellular treatment with membrane permeable Ht31 peptide can impair hippocampal LTP without affecting basal synaptic transmission. These results establish PKA-anchoring via AKAPs as an essential component of PKA function in hippocampal synaptic plasticity.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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