Cited by 203Neuroscience and Neuropharmacology ResearchNicotinic Acetylcholine Receptors StudyNeural dynamics and brain function

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Corelease of acetylcholine and GABA from cholinergic forebrain neurons

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Saunders, Arpiar, Granger, Adam J, Sabatini, Bernardo L·2015·eLife

DOI 10.7554/elife.06412PMC PMC4371381

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Abstract

Neurotransmitter corelease is emerging as a common theme of central neuromodulatory systems. Though corelease of glutamate or GABA with acetylcholine has been reported within the cholinergic system, the full extent is unknown. To explore synaptic signaling of cholinergic forebrain neurons, we activated choline acetyltransferase expressing neurons using channelrhodopsin while recording post-synaptic currents (PSCs) in layer 1 interneurons. Surprisingly, we observed PSCs mediated by GABAA receptors in addition to nicotinic acetylcholine receptors. Based on PSC latency and pharmacological sensitivity, our results suggest monosynaptic release of both GABA and ACh. Anatomical analysis showed that forebrain cholinergic neurons express the GABA synthetic enzyme Gad2 and the vesicular GABA transporter (Slc32a1). We confirmed the direct release of GABA by knocking out Slc32a1 from cholinergic neurons. Our results identify GABA as an overlooked fast neurotransmitter utilized throughout the forebrain cholinergic system. GABA/ACh corelease may have major implications for modulation of cortical function by cholinergic neurons.

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Authors: Saunders, A., Granger, A. J., & Sabatini, B. L.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Sabatini, Bernardo L
ORCID: Saunders, Arpiar
Granger, Adam J
Sabatini, Bernardo L
Venue: eLife
Publisher: eLife Sciences Publications, Ltd
Published: 2015-02-27
Volume: 4
ISSN: 2050-084X (ISSN-L)
DOI: 10.7554/elife.06412
PMC: PMC4371381
OpenAlex: W2142530108
Cited by: 200
References: 45
Citations by year: 2026: 5 · 2025: 17 · 2024: 12 · 2023: 18 · 2022: 21 · 2021: 19 · 2020: 20 · 2019: 24 · 2018: 24 · 2017: 18 · 2016: 19 · 2015: 3
FWCI: 9.95
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
creativecommons.org/licenses/by/4.0/ (am)
creativecommons.org/licenses/by/4.0/ (tdm)
Locations: eLife (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institute of Neurological Disorders and Stroke (NINDS) (#NS072030)
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 › Neural dynamics and brain function
Keywords: acetylcholine, GABA, cholinergic neurons, forebrain, GABAA receptor, nicotinic acetylcholine receptors, choline acetyltransferase, channelrhodopsin, layer 1 interneurons, GAD-2, vesicular GABA transporter, synaptic signaling
MeSH terms: Acetylcholine, Animals, Choline O-Acetyltransferase, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Membrane Potentials, Mice, Transgenic, Synaptic Transmission, Receptors, GABA-A, Receptors, Nicotinic, Tetrodotoxin, 4-Aminopyridine, Prosencephalon, Patch-Clamp Techniques, Microscopy, Confocal, Excitatory Postsynaptic Potentials, Potassium Channel Blockers, Sodium Channel Blockers, Microscopy, Fluorescence, Multiphoton, Vesicular Inhibitory Amino Acid Transport Proteins, Cholinergic Neurons

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Corelease of acetylcholine and GABA from cholinergic forebrain neurons

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