Co-packaging of opposing neurotransmitters in individual synaptic vesicles in the central nervous system.
GABA
basal ganglia
computational modeling
digital micromirror device
entopeduncular nucleus
glutamate
lateral habenula
neurotransmitter co-release
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
20 04 2022
20 04 2022
Historique:
received:
25
03
2021
revised:
16
11
2021
accepted:
06
01
2022
pubmed:
6
2
2022
medline:
26
4
2022
entrez:
5
2
2022
Statut:
ppublish
Résumé
Many mammalian neurons release multiple neurotransmitters to activate diverse classes of postsynaptic ionotropic receptors. Entopeduncular nucleus somatostatin (EP Sst+) projection neurons to the lateral habenula (LHb) release both glutamate and GABA, but it is unclear whether these are packaged into the same or segregated pools of synaptic vesicles. Here, we describe a method combining electrophysiology, spatially patterned optogenetics, and computational modeling designed to analyze the mechanism of glutamate/GABA co-release in mouse brain. We find that the properties of postsynaptic currents elicited in LHb neurons by optogenetically activating EP Sst+ terminals are only consistent with co-packaging of glutamate/GABA into individual vesicles. Furthermore, presynaptic neuromodulators that weaken EP Sst+ to LHb synapses maintain the co-packaging of glutamate/GABA while reducing vesicular release probability. Our approach is applicable to the study of multi-transmitter neurons throughout the brain, and our results constrain the mechanisms of neuromodulation and synaptic integration in LHb.
Identifiants
pubmed: 35120627
pii: S0896-6273(22)00007-1
doi: 10.1016/j.neuron.2022.01.007
pmc: PMC9056948
mid: NIHMS1778555
pii:
doi:
Substances chimiques
Neurotransmitter Agents
0
Glutamic Acid
3KX376GY7L
gamma-Aminobutyric Acid
56-12-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1371-1384.e7Subventions
Organisme : NINDS NIH HHS
ID : R37 NS046579
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS072030
Pays : United States
Organisme : NINDS NIH HHS
ID : K99 NS105883
Pays : United States
Organisme : NINDS NIH HHS
ID : R00 NS105883
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS103226
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests B.L.S. is a member of the Neuron advisory board.
Références
Nature. 2009 Feb 26;457(7233):1142-5
pubmed: 19151697
Elife. 2020 Jul 02;9:
pubmed: 32613945
Neuron. 2017 Apr 5;94(1):138-152.e5
pubmed: 28384468
Cell Rep. 2018 Jun 19;23(12):3465-3479
pubmed: 29924991
J Neurosci. 2014 Oct 15;34(42):13906-10
pubmed: 25319687
Nature. 2007 Jun 28;447(7148):1111-5
pubmed: 17522629
Neuron. 2019 Dec 4;104(5):899-915.e8
pubmed: 31672263
J Neurosci. 2012 Sep 5;32(36):12641-6
pubmed: 22956853
Nat Rev Neurosci. 2020 May;21(5):277-295
pubmed: 32269316
Elife. 2019 Mar 11;8:
pubmed: 30855228
Curr Biol. 2022 Apr 25;32(8):1829-1836.e4
pubmed: 35259343
Neuron. 2010 Dec 22;68(6):1159-72
pubmed: 21172616
Neuron. 2007 Jul 5;55(1):25-36
pubmed: 17610815
Neuropharmacology. 2014 Jun;81:153-65
pubmed: 24508708
Nat Rev Neurosci. 2016 Mar;17(3):139-45
pubmed: 26865019
Mol Psychiatry. 2019 Sep;24(9):1351-1368
pubmed: 30755721
Nature. 2011 Feb 24;470(7335):535-9
pubmed: 21350486
Neuron. 2019 Apr 3;102(1):120-127.e4
pubmed: 30765165
Nat Neurosci. 2016 Aug;19(8):1019-24
pubmed: 27348214
Cold Spring Harb Perspect Biol. 2011 Dec 01;3(12):
pubmed: 22026965
Neuron. 2011 Sep 22;71(6):995-1013
pubmed: 21943598
Proc Natl Acad Sci U S A. 2004 May 4;101(18):7158-63
pubmed: 15103023
Nature. 2018 Feb 14;554(7692):317-322
pubmed: 29446381
J Neurosci. 2000 Jul 1;20(13):4904-11
pubmed: 10864948
Elife. 2015 Feb 27;4:
pubmed: 25723967
J Neurosci. 2016 Jan 13;36(2):302-11
pubmed: 26758824
Neuron. 2008 Nov 26;60(4):720-9
pubmed: 19038227
Science. 1998 Jul 17;281(5375):419-24
pubmed: 9665886
Neuron. 2012 May 10;74(3):475-81
pubmed: 22578499
Cell Rep. 2020 Sep 1;32(9):108094
pubmed: 32877676
Nat Neurosci. 2014 Nov;17(11):1543-51
pubmed: 25242304
Nature. 2012 Oct 11;490(7419):262-6
pubmed: 23034651
Cell. 2006 Nov 17;127(4):831-46
pubmed: 17110340
Nat Neurosci. 2007 May;10(5):663-8
pubmed: 17435752
Nature. 2009 Jun 11;459(7248):837-41
pubmed: 19448610
Nature. 2000 Sep 14;407(6801):189-94
pubmed: 11001057
Nat Neurosci. 2015 Mar;18(3):386-92
pubmed: 25664911
Nature. 2016 Nov 10;539(7628):289-293
pubmed: 27652894
Nat Neurosci. 2014 Sep;17(9):1146-52
pubmed: 25157511
Biophys J. 2009 Mar 4;96(5):1803-14
pubmed: 19254539
Cell. 2017 Jul 13;170(2):284-297.e18
pubmed: 28689640
Nat Neurosci. 2012 Jun 24;15(8):1105-7
pubmed: 22729176
Nature. 2012 Nov 8;491(7423):212-7
pubmed: 23064228
Cell Rep. 2017 Nov 14;21(7):1757-1769
pubmed: 29141211
Science. 2014 Sep 19;345(6203):1494-8
pubmed: 25237099