Evidence map›Paper›PMID 22579668›Full record

ArticleNeuropharmacology2012

CB₂ cannabinoid receptors inhibit synaptic transmission when expressed in cultured autaptic neurons.

Brady K Atwood, Alex Straiker, Ken Mackie

Abstract read
In one paragraph

Article in Neuropharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

23 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Depression of synaptic outputs by reduction of CaFrontiers in molecular neuroscience · 2026
    Article
  3. Article
  4. Mechanisms of cannabinoid tolerance.Biochemical pharmacology · 2023
    Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Mechanisms of cannabinoid CBEBioMedicine · 2019
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. High Times for Painful Blues: The Endocannabinoid System in Pain-Depression Comorbidity.The international journal of neuropsychopharmacology · 2015
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Brady K AtwoodDepartment of Psychological and Brain Sciences, Gill Center for Biomolecular Science, Indiana University, 1101 E. 10th Street, Bloomington, IN 47405, USA. atwoodbk@mail.nih.gov
Alex Straiker
Ken Mackie
Indiana University Bloomington · US

Funding

Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2M
Project 3 - In vivo pharmacology of cannabinoid receptor probesP01DA009158 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI Alexandros Makriyannis · 1994 to 2026
$26.0M
Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
INDIANA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE (UL1): BPCAUL1RR025761 · NCRR · INDIANA UNIVERSITY INDIANAPOLIS · PI SHEKHAR, ANANTHA · 2008 to 2011
$21.0M
Neuronal cannabinoidsR01DA011322 · NIDA · UNIVERSITY OF WASHINGTON · PI MACKIE, KENNETH · 1998 to 2014
$3.4M
Cannabinoid Modulation of Cell FunctionK05DA021696 · NIDA · TRUSTEES OF INDIANA UNIVERSITY · PI MACKIE, KENNETH · 2007 to 2017
$1.3M
NCATS NIH HHS UL1 TR001108NCRR NIH HHS RR025761NCRR NIH HHS UL1 RR025761NIDA NIH HHS DA009158NIDA NIH HHS DA011322NIDA NIH HHS DA021696NIDA NIH HHS K05 DA021696NIDA NIH HHS P01 DA009158NIDA NIH HHS R01 DA011322
6 · The paper itself

Abstract

The role of CB₂ in the central nervous system, particularly in neurons, has generated much controversy. Fueling the controversy are imperfect tools, which have made conclusive identification of CB₂ expressing neurons problematic. Imprecise localization of CB₂ has made it difficult to determine its function in neurons. Here we avoid the localization controversy and directly address the question if CB₂ can modulate neurotransmission. CB₂ was expressed in excitatory hippocampal autaptic neurons obtained from CB₁ null mice. Whole-cell patch clamp recordings were made from these neurons to determine the effects of CB₂ on short-term synaptic plasticity. CB₂ expression restored depolarization induced suppression of excitation to these neurons, which was lost following genetic ablation of CB₁. The endocannabinoid 2-arachidonylglycerol (2-AG) mimicked the effects of depolarization in CB₂ expressing neurons. Interestingly, ongoing basal production of 2-AG resulted in constitutive activation of CB₂, causing a tonic inhibition of neurotransmission that was relieved by the CB₂ antagonist AM630 or the diacylglycerol lipase inhibitor RHC80267. Through immunocytochemistry and analysis of spontaneous EPSCs, paired pulse ratios and coefficients of variation we determined that CB₂ exerts its function at a presynaptic site of action, likely through inhibition of voltage gated calcium channels. Therefore CB₂ expressed in neurons effectively mimics the actions of CB₁. Thus neuronal CB₂ is well suited to integrate into conventional neuronal endocannabinoid signaling processes, with its specific role determined by its unique and highly inducible expression profile.

Indexed as

Synaptic TransmissionAnimalsAnimals, NewbornArachidonic AcidsAstrocytesCells, CulturedEndocannabinoidsEnzyme InhibitorsGlyceridesHeterozygoteHippocampusLipoprotein LipaseMiceMice, KnockoutNerve Tissue ProteinsNeuronsArachidonic AcidsCnr2 protein, mouseEndocannabinoidsEnzyme InhibitorsGlyceridesglyceryl 2-arachidonateLipoprotein LipaseNerve Tissue ProteinsReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2Recombinant Fusion Proteins

Identifiers

PMID22579668
PMCPMC3392362
OpenAlexW2041956252

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.