Evidence map›Paper›PMID 26232789›Full record

ArticleThe international journal of neuropsychopharmacology2015

Impaired 2-AG Signaling in Hippocampal Glutamatergic Neurons: Aggravation of Anxiety-Like Behavior and Unaltered Seizure Susceptibility.

Stephan Guggenhuber, Hector Romo-Parra, Laura Bindila, Julia Leschik, Ermelinda Lomazzo, Floortje Remmers, Tina Zimmermann, Raissa Lerner, Matthias Klugmann, Hans-Christian Pape and 1 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The international journal of neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.8field-weighted citation impact, top 5% 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

36 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Article
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  4. Genetic Tools in Rodents to Study Cannabinoid Functions.Current topics in behavioral neurosciences · 2026
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  8. An Amygdala-hippocampus Circuit for Endocannabinoid Modulation of Anxiety Avoidance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Psychiatric Disorders and Cannabinoid Receptors.Advances in experimental medicine and biology · 2021
    Review
  15. Review
  16. Frontiers in pharmacology · 2021
    Article
  17. Article
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Stephan GuggenhuberInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany (Dr Guggenhuber, Dr Bindila, Dr Leschik, Dr Lomazzo, Dr Remmers, Ms Zimmermann, Ms Lerner, Dr Klugmann, and Dr Lutz); Institute of Physiology I (Neurophysiology), Westfaelische Wilhelms-University, Muenster, Germany (Drs Romo-Parra and Pape); Translational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South Wales, UNSW Kensington Campus, Sydney, NSW, Australia (Dr Klugmann).
Hector Romo-ParraInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany (Dr Guggenhuber, Dr Bindila, Dr Leschik, Dr Lomazzo, Dr Remmers, Ms Zimmermann, Ms Lerner, Dr Klugmann, and Dr Lutz); Institute of Physiology I (Neurophysiology), Westfaelische Wilhelms-University, Muenster, Germany (Drs Romo-Parra and Pape); Translational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South Wales, UNSW Kensington Campus, Sydney, NSW, Australia (Dr Klugmann).
Laura BindilaInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany (Dr Guggenhuber, Dr Bindila, Dr Leschik, Dr Lomazzo, Dr Remmers, Ms Zimmermann, Ms Lerner, Dr Klugmann, and Dr Lutz); Institute of Physiology I (Neurophysiology), Westfaelische Wilhelms-University, Muenster, Germany (Drs Romo-Parra and Pape); Translational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South Wales, UNSW Kensington Campus, Sydney, NSW, Australia (Dr Klugmann).
Julia LeschikInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany (Dr Guggenhuber, Dr Bindila, Dr Leschik, Dr Lomazzo, Dr Remmers, Ms Zimmermann, Ms Lerner, Dr Klugmann, and Dr Lutz); Institute of Physiology I (Neurophysiology), Westfaelische Wilhelms-University, Muenster, Germany (Drs Romo-Parra and Pape); Translational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South Wales, UNSW Kensington Campus, Sydney, NSW, Australia (Dr Klugmann).
Ermelinda LomazzoInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany (Dr Guggenhuber, Dr Bindila, Dr Leschik, Dr Lomazzo, Dr Remmers, Ms Zimmermann, Ms Lerner, Dr Klugmann, and Dr Lutz); Institute of Physiology I (Neurophysiology), Westfaelische Wilhelms-University, Muenster, Germany (Drs Romo-Parra and Pape); Translational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South Wales, UNSW Kensington Campus, Sydney, NSW, Australia (Dr Klugmann).
Floortje RemmersInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany (Dr Guggenhuber, Dr Bindila, Dr Leschik, Dr Lomazzo, Dr Remmers, Ms Zimmermann, Ms Lerner, Dr Klugmann, and Dr Lutz); Institute of Physiology I (Neurophysiology), Westfaelische Wilhelms-University, Muenster, Germany (Drs Romo-Parra and Pape); Translational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South Wales, UNSW Kensington Campus, Sydney, NSW, Australia (Dr Klugmann).
Tina ZimmermannInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany (Dr Guggenhuber, Dr Bindila, Dr Leschik, Dr Lomazzo, Dr Remmers, Ms Zimmermann, Ms Lerner, Dr Klugmann, and Dr Lutz); Institute of Physiology I (Neurophysiology), Westfaelische Wilhelms-University, Muenster, Germany (Drs Romo-Parra and Pape); Translational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South Wales, UNSW Kensington Campus, Sydney, NSW, Australia (Dr Klugmann).
Raissa LernerInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany (Dr Guggenhuber, Dr Bindila, Dr Leschik, Dr Lomazzo, Dr Remmers, Ms Zimmermann, Ms Lerner, Dr Klugmann, and Dr Lutz); Institute of Physiology I (Neurophysiology), Westfaelische Wilhelms-University, Muenster, Germany (Drs Romo-Parra and Pape); Translational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South Wales, UNSW Kensington Campus, Sydney, NSW, Australia (Dr Klugmann).
Matthias KlugmannInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany (Dr Guggenhuber, Dr Bindila, Dr Leschik, Dr Lomazzo, Dr Remmers, Ms Zimmermann, Ms Lerner, Dr Klugmann, and Dr Lutz); Institute of Physiology I (Neurophysiology), Westfaelische Wilhelms-University, Muenster, Germany (Drs Romo-Parra and Pape); Translational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South Wales, UNSW Kensington Campus, Sydney, NSW, Australia (Dr Klugmann).
Hans-Christian PapeInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany (Dr Guggenhuber, Dr Bindila, Dr Leschik, Dr Lomazzo, Dr Remmers, Ms Zimmermann, Ms Lerner, Dr Klugmann, and Dr Lutz); Institute of Physiology I (Neurophysiology), Westfaelische Wilhelms-University, Muenster, Germany (Drs Romo-Parra and Pape); Translational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South Wales, UNSW Kensington Campus, Sydney, NSW, Australia (Dr Klugmann).
Beat LutzInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany (Dr Guggenhuber, Dr Bindila, Dr Leschik, Dr Lomazzo, Dr Remmers, Ms Zimmermann, Ms Lerner, Dr Klugmann, and Dr Lutz); Institute of Physiology I (Neurophysiology), Westfaelische Wilhelms-University, Muenster, Germany (Drs Romo-Parra and Pape); Translational Neuroscience Facility, Department of Physiology, School of Medical Sciences, University of New South Wales, UNSW Kensington Campus, Sydney, NSW, Australia (Dr Klugmann). blutz@uni-mainz.de.
Johannes Gutenberg University Mainz · DEUniversity Medical Center of the Johannes Gutenberg University Mainz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPostsynaptically generated 2-arachidonoylglycerol activates the presynaptic cannabinoid type-1 receptor, which is involved in synaptic plasticity at both glutamatergic and GABAergic synapses. However, the differential function of 2-arachidonoylglycerol signaling at glutamatergic vs GABAergic synapses in the context of animal behavior has not been investigated yet.

methodsHere, we analyzed the role of 2-arachidonoylglycerol signaling selectively in hippocampal glutamatergic neurons. Monoacylglycerol lipase, the primary degrading enzyme of 2-arachidonoylglycerol, is expressed at presynaptic sites of excitatory and inhibitory neurons. By adeno-associated virus-mediated overexpression of monoacylglycerol lipase in glutamatergic neurons of the mouse hippocampus, we selectively interfered with 2-arachidonoylglycerol signaling at glutamatergic synapses of these neurons.

resultsGenetic modification of monoacylglycerol lipase resulted in a 50% decrease in 2-arachidonoylglycerol tissue levels without affecting the content of the second major endocannabinoid anandamide. A typical electrophysiological read-out for 2-arachidonoylglycerol signaling is the depolarization-induced suppression of excitation and of inhibition. Elevated monoacylglycerol lipase levels at glutamatergic terminals selectively impaired depolarization-induced suppression of excitation, while depolarization-induced suppression of inhibition was not significantly changed. At the behavioral level, mice with impaired hippocampal glutamatergic 2-arachidonoylglycerol signaling exhibited increased anxiety-like behavior but showed no alterations in aversive memory formation and seizure susceptibility.

conclusionOur data indicate that 2-arachidonoylglycerol signaling selectively in hippocampal glutamatergic neurons is essential for the animal's adaptation to aversive situations.

Indexed as

AnimalsAnxietyArachidonic AcidsEndocannabinoidsGlutamic AcidGlyceridesHippocampusMaleMiceMice, Inbred C57BLNeuronsSeizuresSignal TransductionArachidonic AcidsEndocannabinoidsGlutamic AcidGlyceridesglyceryl 2-arachidonateanxietyendocannabinoidsepilepsyhippocampusMonoacylglycerol lipase

Identifiers

PMID26232789
PMCPMC4772822
OpenAlexW2115136745

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.