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No evidence for role of extracellular choline-acetyltransferase in generation of gamma oscillations in rat hippocampal slices in vitro.
- Source :
-
Neuroscience [Neuroscience] 2015 Jan 22; Vol. 284, pp. 459-469. Date of Electronic Publication: 2014 Oct 16. - Publication Year :
- 2015
-
Abstract
- Acetylcholine (ACh) is well known to induce persistent γ-oscillations in the hippocampus when applied together with physostigmine, an inhibitor of the ACh degrading enzyme acetylcholinesterase (AChE). Here we report that physostigmine alone can also dose-dependently induce γ-oscillations in rat hippocampal slices. We hypothesized that this effect was due to the presence of choline in the extracellular space and that this choline is taken up into cholinergic fibers where it is converted to ACh by the enzyme choline-acetyltransferase (ChAT). Release of ACh from cholinergic fibers in turn may then induce γ-oscillations. We therefore tested the effects of the choline uptake inhibitor hemicholinium-3 (HC-3) on persistent γ-oscillations either induced by physostigmine alone or by co-application of ACh and physostigmine. We found that HC-3 itself did not induce γ-oscillations and also did not prevent physostigmine-induced γ-oscillation while washout of physostigmine and ACh-induced γ-oscillations was accelerated. It was recently reported that ChAT might also be present in the extracellular space (Vijayaraghavan et al., 2013). Here we show that the effect of physostigmine was prevented by the ChAT inhibitor (2-benzoylethyl)-trimethylammonium iodide (BETA) which could indicate extracellular synthesis of ACh. However, when we tested for effects of extracellularly applied acetyl-CoA, a substrate of ChAT for synthesis of ACh, physostigmine-induced γ-oscillations were attenuated. Together, these findings do not support the idea that ACh can be synthesized by an extracellularly located ChAT.<br /> (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- Acetyl Coenzyme A administration & dosage
Acetyl Coenzyme A metabolism
Acetylcholine administration & dosage
Acetylcholine analogs & derivatives
Acetylcholine metabolism
Acetylcholine pharmacology
Animals
CA3 Region, Hippocampal drug effects
Choline metabolism
Choline O-Acetyltransferase antagonists & inhibitors
Cholinergic Agents pharmacology
Cholinesterase Inhibitors pharmacology
Dose-Response Relationship, Drug
Gamma Rhythm drug effects
Hemicholinium 3 pharmacology
Male
Microelectrodes
Neurotransmitter Uptake Inhibitors pharmacology
Physostigmine pharmacology
Rats, Wistar
Tissue Culture Techniques
CA3 Region, Hippocampal enzymology
Choline O-Acetyltransferase metabolism
Extracellular Space enzymology
Gamma Rhythm physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7544
- Volume :
- 284
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 25453770
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2014.10.016