Neuroscience 2005 Abstract
| Presentation Number: | 611.11 |
|---|---|
| Abstract Title: | Learning and memory impairment by the general anesthetic etomidate is mediated by α5 GABA<sub>A</sub> receptors. |
| Authors: |
Martin, L. J.*1
; Cheng, V. Y.1
; MacDonald, J. F.2
; Wafford, K. A.4
; Orser, B. A.1,2,3
1Inst. of Medical Science, Univ. of Toronto, Toronto, Canada 2Physiology, Univ. of Toronto, Toronto, Canada 3Anesthesia, Univ. of Toronto, Toronto, Canada 4United Kingdom, 1 King's College Circle, M5S 1A8, |
| Primary Theme and Topics |
Neural Excitability, Synapses, and Glia: Cellular Mechanisms - Synaptic Plasticity -- LTP: Physiology and behavior |
| Secondary Theme and Topics | Neural Excitability, Synapses, and Glia: Cellular Mechanisms<br />- Ligand-Gated Ion Channels<br />-- GABAa receptors: Physiology |
| Session: |
611. LTP Physiology and Behavior: Genes and Behavior Poster |
| Presentation Time: | Tuesday, November 15, 2005 10:00 AM-11:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # F1 |
| Keywords: | GABA RECEPTOR, LEARNING AND MEMORY, LTP, WATER MAZE |
GABAA receptors containing the α5 subunit (α5GABAARs) are predominantly expressed in the hippocampus of the mammalian brain. α5GABAARs have been implicated in learning and memory, as α5 null mutant mice (KO) show enhanced performance in hippocampal-dependent tasks (J Neurosci 22(13):5572). We recently showed that α5GABAARs generate a tonic but not synaptic current in murine CA1 pyramidal neurons (PNAS 101:3662). Further, low concentrations of the anesthetic, etomidate selectively enhance the tonic but not synaptic currents in hippocampal neurons (SFN Abstract 2003 #571.2). Our aim was to determine if α5GABAARs contribute to the amnestic effects of anesthetics. Here we report that etomidate (0.1 µM) potentiated a tonic current in wild-type (WT) (29.7 ± 13.9 pA, n=7) but not KO neurons (4.2 ± 2.2 pA, n=7, p<0.05). Etomidate (1 µM) impaired long-term potentiation (LTP; theta-burst protocol) in CA1 pyramidal neurons from WT (149.9 ± 9.3%, n=4 vs.109.8 ± 11.4%, n=4: control vs. etomidate) but not in KO mice (161.8 ± 7.3%, n=6 vs. 171.3 ± 12.5 %, n=6, p<0.05). Behavioural studies showed that learning and memory performance of WT but not KO mice was impaired by a low dose of etomidate (4 mg/kg; i.p.). Contextual fear conditioning indicated that etomidate impaired freezing in WT but not KO mice. During probe trials of the Morris water maze, time spent swimming in the correct quadrant of the pool was reduced in WT but not KO mice when etomidate was administered during the acquisition (i.e., learning) phase of the task. The WT and KO mice are phenotypically similar and do not differ with respect to sedation, motor impairment or anxiety levels. Our results suggest that increasing tonic inhibition in the hippocampus by low doses of etomidate underlies learning and memory impairment.
Supported by CIHR and Merck Sharpe & Dohme
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
Copyright © 2005-2025 Society for Neuroscience; all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
