Corelease of acetylcholine and GABA from cholinergic forebrain neurons

ELife
Arpiar SaundersBernardo L Sabatini

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.

References

May 10, 1995·Annals of the New York Academy of Sciences·M M Mesulam
Mar 28, 1998·Science·M P Kilgard, M M Merzenich
Jul 17, 1998·Science·P JonasJ Sandkühler
Jan 1, 1999·Trends in Pharmacological Sciences·J J Soghomonian, D L Martin
Jan 22, 2000·Brain Research Bulletin·P Strata, R Harvey
Mar 23, 2004·Nature Reviews. Neuroscience·Norman M Weinberger
May 17, 2006·Neuron·Sonja M WojcikJeong-Seop Rhee
May 25, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nicolas WanaverbecqDimitri M Kullmann
Feb 19, 2008·Nature Neuroscience·Christelle GrasSalah El Mestikawy
Jan 23, 2009·Nature Neuroscience·Qingchun TongBradford B Lowell
Apr 21, 2009·Nature Reviews. Neuroscience·Martin SarterW Matthew Howe
May 8, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dhakshin RamanathanJames M Conner
May 21, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Fatuel TecuapetlaTibor Koos
Jun 18, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Garret D StuberAntonello Bonci
Nov 8, 2011·Annual Review of Physiology·Thomas S Hnasko, Robert H Edwards
Dec 14, 2011·Nature·Johannes J LetzkusAndreas Lüthi
Mar 13, 2012·International Journal of Molecular Sciences·Miroslav Pohanka
Mar 17, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sergio ArroyoShaul Hestrin
Jun 5, 2012·Nature·Yevgenia KozorovitskiyBernardo L Sabatini
Oct 5, 2012·Nature·Nicolas X TritschBernardo L Sabatini
Dec 1, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Corbett BennettShaul Hestrin
Oct 29, 2013·Nature Neuroscience·Lucas PintoYang Dan
Mar 7, 2014·The European Journal of Neuroscience·Martin SarterAnne S Berry
Mar 19, 2014·Cell·Yu FuMichael P Stryker
Mar 25, 2014·Neuron·Zhixiang LiuMinmin Luo
Jun 1, 2014·The Journal of Physiology·Rogier B PoorthuisJohannes J Letzkus
Jun 27, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alexandra B NelsonRebecca P Seal
Sep 23, 2014·Nature Neuroscience·David H RootMarisela Morales
Mar 6, 2015·Nature·Arpiar SaundersBernardo L Sabatini

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Citations

Feb 13, 2016·Nature Reviews. Neuroscience·Nicolas X TritschBernardo L Sabatini
Feb 3, 2016·Brain Structure & Function·S MongiaE Mengual
Jul 30, 2015·Neuropharmacology·Adam J GrangerBernardo L Sabatini
Jan 24, 2016·Cerebral Cortex·Mohammed A Al-OnaiziVania F Prado
Jan 15, 2016·Journal of Chemical Neuroanatomy·David J BarkerMarisela Morales
Jan 21, 2016·Proceedings of the National Academy of Sciences of the United States of America·Howard J GrittonMartin Sarter
Jun 8, 2015·Neuron·Nicholas C Spitzer
Apr 11, 2015·Progress in Neurobiology·David H RootT Celeste Napier
May 31, 2016·Neuron·Santhosh SethuramanujamGautam B Awatramani
Sep 20, 2016·Neuroscience·Vania F PradoMarco A M Prado
Sep 23, 2016·Wiley Interdisciplinary Reviews. Cognitive Science·Sandra IglesiasKlaas E Stephan
Nov 20, 2016·The Journal of Comparative Neurology·Miriam BarnerssoiAnja K E Horn
Jun 26, 2017·Pharmacology, Biochemistry, and Behavior·Daniel S Zahm, David H Root
Mar 1, 2018·Proceedings of the National Academy of Sciences of the United States of America·Srinidhi DesikanHannah Monyer
May 4, 2018·CNS Neuroscience & Therapeutics·Francisco E Olucha-BordonauAndrew L Gundlach
Feb 6, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Olga DergachevaDavid Mendelowitz
Oct 5, 2016·Nature·Alexander M HermanBenjamin R Arenkiel
Jul 29, 2018·The European Journal of Neuroscience·Nicola Solari, Balázs Hangya
Feb 19, 2019·The Journal of Comparative Neurology·Ida Luisa BoccalaroLena Rubi
Mar 29, 2019·The Journal of Physiology·Alvaro Sanz DiezDidier De Saint Jan
Dec 11, 2019·The European Journal of Neuroscience·Yann S Mineur, Marina R Picciotto
Feb 7, 2020·PLoS Biology·Amir DudaiMichael London
Jul 2, 2020·Journal of Neurophysiology·Zhou YuElisabeth Glowatzki
Apr 27, 2019·Frontiers in Immunology·Kurt R LehnerValentin A Pavlov
Feb 6, 2020·Protoplasma·Gusel V Sibgatullina, Artem I Malomouzh
Feb 8, 2019·Frontiers in Neural Circuits·Erik SvenssonHelgi B Schiöth
Feb 15, 2020·Journal of Neuroscience Research·Anne L Collins, Benjamin T Saunders
Aug 5, 2020·Nature Reviews. Neuroscience·Sarah Melzer, Hannah Monyer
Nov 8, 2017·The Journal of Physiology·Paul G AnastasiadesSimon J B Butt
Jun 3, 2017·Cold Spring Harbor Protocols·Michael Beierlein
Jul 11, 2018·Frontiers in Physiology·Shreyas JoisAdelaine Kwun-Wai Leung
Sep 26, 2019·Frontiers in Molecular Neuroscience·Noorya Yasmin AhmedNathalie Dehorter

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Methods Mentioned

BETA
transgenic

Software Mentioned

Igor Pro
MATLAB
ImageJ
ScanImage
GraphPad Prism

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