Cited by 150Neuroscience and Neuropharmacology ResearchNicotinic Acetylcholine Receptors StudyMemory and Neural Mechanisms

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Cholinergic Modulation of Excitatory Synaptic Transmission in the CA3 Area of the Hippocampus

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Vogt, Kaspar E., Regehr, Wade G.·2001·The Journal of Neuroscience

DOI 10.1523/jneurosci.21-01-00075.2001PMC PMC6762445

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Abstract

Cholinergic innervation of the hippocampus has been implicated in memory formation and retrieval. Here we study cholinergic modulation of excitatory transmission in the CA3 area of the rat hippocampus. We used a combination of optical measurements of presynaptic calcium and electrophysiological measurements of synaptic currents to study associational–commissural (A/C) and mossy fiber (MF) synapses in brain slices. Direct synaptic modulation mediated by ACh receptors is only evident at the A/C synapse, where synaptic inhibition primarily reflects presynaptic calcium channel inhibition mediated by muscarinic receptors. MF synapses can, however, be indirectly modulated by muscarinic receptor activation. Muscarine elevates the firing rate of inhibitory cells, which increases GABA release and inhibits MF synapses by activating presynaptic GABA B receptors. Muscarine also depolarizes dentate granule cells and elevates their rate of firing. This leads to synaptic enhancement when combined with the use-dependent facilitation of MF synapses. In addition we were unable to evoke an increase in presynaptic calcium levels in MF boutons with local application of nicotinic receptor agonists. This finding does not support a leading hypothesis for MF modulation in which activation of presynaptic nicotinic receptors enhances transmission directly by elevating presynaptic calcium levels. However, indirect synaptic modulation could arise from nicotinic excitation of inhibitory neurons. Thus, to understand cholinergic modulation within the CA3 region, it is necessary to take into account secondary actions on synapses arising from other chemical messengers released by other cell types and to consider effects on firing patterns of presynaptic cells, which in turn influence release via use-dependent synaptic plasticity.

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Self-citation

Authors: Vogt, K. E., & Regehr, W. G.
Affiliations: Harvard University (US)
ORCID: Vogt, Kaspar E.
Regehr, Wade G.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2001-01-01
Volume: 21
Issue: 1
Pages: 75-83
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.21-01-00075.2001
PMC: PMC6762445
OpenAlex: W2125706064
Cited by: 149
References: 49
Citations by year: 2025: 4 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 5 · 2012: 10
FWCI: 4.56
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 181 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
National Institutes of Health
U.S. Public Health Service (P01-N538312)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: cholinergic modulation, excitatory synaptic transmission, hippocampal CA3, muscarinic receptors, nicotinic acetylcholine receptors, mossy fiber synapses, presynaptic calcium, GABAergic inhibition, GABAB receptors, dentate gyrus granule cells, synaptic plasticity, acetylcholine
MeSH terms: Animals, Calcium, Cholinergic Fibers, Fluorescent Dyes, Hippocampus, Muscarine, Synaptic Transmission, Nicotine, Synapses, Fura-2, Rats, Sprague-Dawley, Pyramidal Cells, Receptors, Metabotropic Glutamate, Patch-Clamp Techniques, Cholinergic Agonists, Glutamic Acid, Nicotinic Agonists, Mossy Fibers, Hippocampal, Excitatory Postsynaptic Potentials, Rats, GABA-B Receptor Agonists, GABA-A Receptor Antagonists, GABA-B Receptor Antagonists, In Vitro Techniques

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Cholinergic Modulation of Excitatory Synaptic Transmission in the CA3 Area of the Hippocampus

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