Evidence map›Paper›PMID 35120627›Full record

ArticleNeuron2022

Co-packaging of opposing neurotransmitters in individual synaptic vesicles in the central nervous system.

SeulAh Kim, Michael L Wallace, Mahmoud El-Rifai, Alexa R Knudsen, Bernardo L Sabatini

Open access · greenAbstract read
In one paragraph

Article in Neuron, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
5.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 54 citations in OpenAlex.

  1. Review
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  10. Dopamine-Glutamate and Dopamine-GABA Co-release.Advances in neurobiology · 2025
    Review
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  19. Prevalent co-release of glutamate and GABA throughout the mouse brain.bioRxiv : the preprint server for biology · 2024
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

SeulAh KimHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, 220 Longwood Ave, Boston, MA 02115, USA.
Michael L WallaceHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, 220 Longwood Ave, Boston, MA 02115, USA.
Mahmoud El-RifaiDepartment of Neurobiology, Harvard Medical School, 220 Longwood Ave, Boston, MA 01225, USA.
Alexa R KnudsenHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, 220 Longwood Ave, Boston, MA 02115, USA.
Bernardo L SabatiniHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, 220 Longwood Ave, Boston, MA 02115, USA. Electronic address: bsabatini@hms.harvard.edu.
Howard Hughes Medical Institute · USHarvard University · US

Funding

Super-Resolution ImagingP30NS072030 · NINDS · HARVARD MEDICAL SCHOOL · PI REGEHR, WADE G · 2011 to 2020
$5.8M
Action and interaction of ionotropic and metabotropic neurotransmissionR37NS046579 · NINDS · HARVARD MEDICAL SCHOOL · PI SABATINI, BERNARDO L · 2018 to 2024
$4.6M
Serotonergic modulation of the circuits and cell-types of the lateral habenulaR01MH133608 · NIMH · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Michael L Wallace · 2023 to 2026
$2.4M
Structure and function of the mouse parafasicular and entopeduncular nucleiR01NS103226 · NINDS · HARVARD MEDICAL SCHOOL · PI OSTEN, PAVEL, SABATINI, BERNARDO L · 2017 to 2021
$2.1M
A Function for the Entopeduncular Nucleus in Motivated BehaviorR00NS105883 · NINDS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI WALLACE, MICHAEL L · 2021 to 2023
$744k
Defining a Role for the Entopeduncular Nucleus in Motivated BehaviorK99NS105883 · NINDS · HARVARD MEDICAL SCHOOL · PI WALLACE, MICHAEL L · 2018 to 2019
$179k
Howard Hughes Medical InstituteNIMH NIH HHS R01 MH133608NINDS NIH HHS K99 NS105883NINDS NIH HHS P30 NS072030NINDS NIH HHS R00 NS105883NINDS NIH HHS R01 NS103226NINDS NIH HHS R37 NS046579
6 · The paper itself

Abstract

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.

Indexed as

HabenulaSynaptic VesiclesAnimalsgamma-Aminobutyric AcidGlutamic AcidMammalsMiceNeurotransmitter Agentsgamma-Aminobutyric AcidGlutamic AcidNeurotransmitter Agentsbasal gangliacomputational modelingdigital micromirror deviceentopeduncular nucleusGABAglutamatelateral habenulaneurotransmitter co-release

Identifiers

PMID35120627
PMCPMC9056948
OpenAlexW4210791415

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.