2-Arachidonoylglycerol mobilization following brief synaptic stimulation in the dorsal lateral striatum requires glutamatergic and cholinergic neurotransmission. (1st March 2022)

• Record Type: Journal Article
• Authors: Liput, Daniel J.; Puhl, Henry L.; Dong, Ao; He, Kaikai; Li, Yulong; Lovinger, David M.
• Is Part Of: Neuropharmacology. Volume 205(2022)
• Publication Date: 2022-03-01
• Subjects: Endocannabinoids -- Glutamate -- Acetylcholine -- Muscarinic receptors -- Dopamine -- Striatum -- Genetically encoded biosensor; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2021.108916
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Several forms of endocannabinoid (eCB) signaling have been described in the dorsal lateral striatum (DLS), however most experimental protocols used to generate eCBs do not recapitulate the firing patterns of striatal-projecting pyramidal neurons in the cortex or firing patterns of striatal medium spiny neurons. Therefore, it is unclear if current models of eCB signaling in the DLS provide a reliable description of mechanisms engaged under physiological conditions. To address this uncertainty, we investigated mechanisms of eCB mobilization following brief synaptic stimulation that mimics in vivo patterns of neural activity in the DLS. To monitor eCB mobilization, the novel genetically encoded fluorescent eCB biosensor, GRABeCB2.0, was expressed presynaptically in corticostriatal afferents of C57BL6J mice and evoked eCB transients were measured in the DLS using a brain slice photometry technique. We found that brief bouts of synaptic stimulation induce long lasting eCB transients that were generated predominantly by 2-arachidonoylglycerol (2-AG) mobilization. Efficient 2-AG mobilization required coactivation of AMPA and NMDA ionotropic glutamate receptors and muscarinic M1 receptors. Dopamine D2 receptors expressed on cholinergic interneurons inhibited 2-AG mobilization by inhibiting acetylcholine release. Collectively, these data uncover unrecognized mechanisms underlying 2-AG mobilization in the DLS. Highlights: The genetically-encoded fluorescent biosensor, GRABeCB2.0, detects presynaptic 2-AG transients in striatal brain slices. Brief bouts of synaptic stimulation, mimicking in vivo patterns of neural activity, induce long lasting 2-AG transients. 2-AG mobilization requires co-activation of ionotropic glutamate receptors and muscarinic M1 receptors. Cholinergic interneurons are required for 2-AG mobilization.