Galantamine increases excitability of CA1 hippocampal pyramidal neurons

Oh, M. M., Wu, W. W., Power, J. M. and Disterhoft, J. F. (2006) Galantamine increases excitability of CA1 hippocampal pyramidal neurons. Neuroscience, 137 1: 113-123. doi:10.1016/j.neuroscience.2005.08.063


Author Oh, M. M.
Wu, W. W.
Power, J. M.
Disterhoft, J. F.
Title Galantamine increases excitability of CA1 hippocampal pyramidal neurons
Journal name Neuroscience   Check publisher's open access policy
ISSN 0306-4522
Publication date 2006
Sub-type Article (original research)
DOI 10.1016/j.neuroscience.2005.08.063
Volume 137
Issue 1
Start page 113
End page 123
Total pages 11
Place of publication Oxford
Publisher Pergamon-elsevier Science Ltd
Language eng
Abstract Galantamine is a third generation cholinesterase inhibitor and an allosteric potentiating ligand of nicotinic acetylcholine receptors. It enhances learning in aging rabbits and alleviates cognitive deficits observed in patients with Alzheimer's disease. We examined galantamine's effect on CA1 neurons from hippocampal slices of young and aging rabbits using current-clamp, intracellular recording techniques. Galantamine (10-200 mu M) dose-dependently reduced the postburst afterhyperpolarization and the spike-frequency accommodation of CA1 neurons from both young and aging animals. These reductions were partially, but significantly, reversed by the addition of the muscarinic receptor antagonist, atropine (1 mu M), to the perfusate. In contrast, the nicotinic acetylcholine receptor antagonist, a-bungarotoxin (10 nM), had no effect; i.e. a-bungarotoxin did not reverse the afterhyperpolarization and accommodation reductions. The allosteric potentiating ligand effect was examined by stimulating the Schaffer collateral and measuring the excitatory postsynaptic potentials for 30 min during bath application of galantamine. Galantamine (200 mu M) significantly enhanced the excitatory postsynaptic potential amplitude and area over time. These effects were blocked by 10 nM a-bungarotoxin, supporting a role for galantamine as an allosteric potentiating ligand. We did not observe a facilitation of the excitatory postsynaptic potentials with 1 mu M galantamine. However, when the excitatory postsynaptic potential was pharmacologically isolated by adding 10 mu M gabazine (GABA(A) receptor antagonist) to the perfusate, 1 mu M galantamine potentiated the subthreshold excitatory postsynaptic potentials into action potentials. We propose that the learning enhancement observed in aging animals and the alleviation of cognitive deficits associated with Alzheimer's disease after galantamine treatment may in part be due to the enhanced function of both nicotinic and muscarinic excitatory transmission on hippocampal pyramidal neurons. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.
Keyword Neurosciences
afterhyperpolarization
aging
Alzheimer's disease
cholinesterase inhibitor
muscarinic
nicotinic
Nicotinic Acetylcholine-receptors
Placebo-controlled Trial
Central-nervous-system
Alzheimers-disease
Synaptic Transmission
Facilitates Acquisition
Enhances Excitability
Protein-kinase
Aging Rabbits
Human-brain
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Queensland Brain Institute Publications
 
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Created: Fri, 25 Jan 2008, 16:44:54 EST