ArticleFrontiers in cellular neuroscience2015
Endocannabinoids Mediate Muscarinic Acetylcholine Receptor-Dependent Long-Term Depression in the Adult Medial Prefrontal Cortex.
Article in Frontiers in cellular neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 43 citations in OpenAlex.
- GluD1 is localized at cholinergic synapses and is an acetylcholine receptor.Molecular psychiatry · 2026Article
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- Distinct synaptic mechanisms drive the behavioral response to acute stress and rapid correction by ketamine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Cholinergic Control of GnRH Neuron Physiology and Luteinizing Hormone Secretion in Male Mice: Involvement of ACh/GABA Cotransmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- A Complete Endocannabinoid Signaling System Modulates Synaptic Transmission between Human Induced Pluripotent Stem Cell-Derived Neurons.Molecular pharmacology · 2023Article
- Targeting muscarinic receptors to treat schizophrenia.Behavioural brain research · 2021Review
- Impairment of Synaptic Plasticity by Cannabis, ΔCold Spring Harbor perspectives in medicine · 2021Review
- Plasticity in Prefrontal Cortex Induced by Coordinated Synaptic Transmission Arising from Reuniens/Rhomboid Nuclei and Hippocampus.Cerebral cortex communications · 2021Article
- Layer-specific serotonergic induction of long-term depression in the prefrontal cortex of rats.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2020Article
- Perinatal THC exposure via lactation induces lasting alterations to social behavior and prefrontal cortex function in rats at adulthood.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- Biased MScience signaling · 2019Article
- Retrograde activation of CB1R by muscarinic receptors protects against central organophosphorus toxicity.Neuropharmacology · 2019Article
- PF-06827443 Displays Robust Allosteric Agonist and Positive Allosteric Modulator Activity in High Receptor Reserve and Native Systems.ACS chemical neuroscience · 2018Article
- Article
- MNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Role of mGluACS chemical neuroscience · 2017Article
- Endocannabinoid Mediates Excitatory Synaptic Function of β-Neurexins. Commentary: β-Neurexins Control Neural Circuits by Regulating Synaptic Endocannabinoid Signaling.Frontiers in neuroscience · 2016Article
- Cannabinoid receptor type-1: breaking the dogmas.F1000Research · 2016Review
- Article
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7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholinergic inputs into the prefrontal cortex (PFC) are associated with attention and cognition; however there is evidence that acetylcholine also has a role in PFC dependent learning and memory. Muscarinic acetylcholine receptors (mAChR) in the PFC can induce synaptic plasticity, but the underlying mechanisms remain either opaque or unresolved. We have characterized a form of mAChR mediated long-term depression (LTD) at glutamatergic synapses of layer 5 principal neurons in the adult medial PFC. This mAChR LTD is induced with the mAChR agonist carbachol and inhibited by selective M1 mAChR antagonists. In contrast to other cortical regions, we find that this M1 mAChR mediated LTD is coupled to endogenous cannabinoid (eCB) signaling. Inhibition of the principal eCB CB1 receptor blocked carbachol induced LTD in both rats and mice. Furthermore, when challenged with a sub-threshold carbachol application, LTD was induced in slices pretreated with the monoacylglycerol lipase (MAGL) inhibitor JZL184, suggesting that the eCB 2-arachidonylglyerol (2-AG) mediates M1 mAChR LTD. Yet, when endogenous acetylcholine was released from local cholinergic afferents in the PFC using optogenetics, it failed to trigger eCB-LTD. However coupling patterned optical and electrical stimulation to generate local synaptic signaling allowed the reliable induction of LTD. The light-electrical pairing induced LTD was M1 mAChR and CB1 receptor mediated. This shows for the first time that connecting excitatory synaptic activity with coincident endogenously released acetylcholine controls synaptic gain via eCB signaling. Together these results shed new light on the mechanisms of synaptic plasticity in the adult PFC and expand on the actions of endogenous cholinergic signaling.
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