Neuroscience 2005 Abstract
| Presentation Number: | 159.6 |
|---|---|
| Abstract Title: | cAMP-mediated changes in AMPA receptor dynamics dependent on Epac. |
| Authors: |
Kiraly, D. D.*1
; Olausson, P.1
; Matsuzaki, H.1
; Nairn, A. C.1
; Taylor, J. R.1
1Department of Psychiatry, Yale Univ., New Haven, CT |
| Primary Theme and Topics |
Neural Excitability, Synapses, and Glia: Cellular Mechanisms - Synaptic Plasticity -- LTP: Kinases and intracellular signaling |
| Session: |
159. LTP Signaling: PKA and ERK Poster |
| Presentation Time: | Sunday, November 13, 2005 9:00 AM-10:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # K5 |
| Keywords: | learning, memory, cAMP, PKA |
Exchange protein activated directly by cAMP (Epac) is a recently discovered target of the second messenger molecule cAMP. While the functional consequences of activating the cAMP target protein kinase A (PKA) have been extensively characterized in neurons, little is known about the role of Epac activation. Epac is highly expressed in hippocampus and may influence neuroplasticity and learning and memory processes. Infusion of the selective Epac agonist 8-pCPT-cAMP into rat dorsal hippocampus impaired contextual fear conditioning (see SFN abstract Olausson et al.). Biochemical analysis of these hippocampi revealed a subunit-specific cleavage of the extreme C-terminus of the GluR1 AMPA receptor subunit. Subsequent experiments implicated calpain in this effect (see SFN abstract Matsuzaki et al.). These studies suggest that activation of Epac may affect AMPA receptor function and/or dynamics, though further studies are needed to determine the effect of this cleavage on GluR1 receptors. To test the hypothesis that Epac activation influences receptor trafficking we used an in vitro hippocampal cell culture system in which AMPA receptor dynamics could be monitored. In order to measure cell surface expression of AMPA receptors we used biotinylation techniques to examine plasma membrance surface expression at various time points after agonist-induced activation of Epac. These studies showed that 8-pCPT-cAMP caused a time-dependent decrease in surface expression of GluR1 subunits. Additionally, in this cell culture system after NMDA-induced AMPA receptor internalization, activation of Epac interfered with the reinsertion of the receptors into the membrane. Taken together, these results indicate that Epac may be involved in the trafficking of AMPA receptors away from the membrane, as well as actively interfering with their insertion into the membrane. These biochemical effects of Epac activation may contribute to aspects of plasticity involved in learning and memory processes.
Supported by DA15222 (JRT) and DA10044 (ACN)
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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