Lack of the Transient Receptor Potential Vanilloid 1 Shifts Cannabinoid-Dependent Excitatory Synaptic Plasticity in the Dentate Gyrus of the Mouse Brain Hippocampus

• Published in: Frontiers in neuroanatomy Vol. 15; p. 701573
• Main Authors: Egaña-Huguet, Jon, Saumell-Esnaola, Miquel, Achicallende, Svein, Soria-Gomez, Edgar, Bonilla-Del Río, Itziar, García del Caño, Gontzal, Barrondo, Sergio, Sallés, Joan, Gerrikagoitia, Inmaculada, Puente, Nagore, Elezgarai, Izaskun, Grandes, Pedro
• Format: Journal Article
• Language: English
• Published: Lausanne Frontiers Research Foundation 07.07.2021; Frontiers Media S.A
• Subjects: 2-Arachidonoylglycerol; Actin; Biotechnology; Brain; Cannabinoid CB1 receptors; Capsaicin receptors; CB1 receptor; Cold; Dendritic spines; Dentate gyrus; endovanilloid system; excitatory synapses; Experiments; Filaments; G proteins; Guanine; Hippocampus; Long-term depression; Long-term potentiation; Neuroscience; Nitric oxide; Sucrose; Synaptic depression; Synaptic plasticity; Synaptosomes; Transient receptor potential proteins; United States > US
• ISSN: 1662-5129; 1662-5129
• DOI: 10.3389/fnana.2021.701573

The transient receptor potential vanilloid 1 (TRPV1) participates in synaptic functions in the brain. In the dentate gyrus, post-synaptic TRPV1 in the granule cell (GC) dendritic spines mediates a type of long-term depression (LTD) of the excitatory medial perforant path (MPP) synapses independent of pre-synaptic cannabinoid CB 1 receptors. As CB 1 receptors also mediate LTD at these synapses, both CB 1 and TRPV1 might be influencing the activity of each other acting from opposite synaptic sites. We tested this hypothesis in the MPP–GC synapses of mice lacking TRPV1 (TRPV1-/-). Unlike wild-type (WT) mice, low-frequency stimulation (10 min at 10 Hz) of TRPV1-/- MPP fibers elicited a form of long-term potentiation (LTP) that was dependent on (1) CB 1 receptors, (2) the endocannabinoid 2-arachidonoylglycerol (2-AG), (3) rearrangement of actin filaments, and (4) nitric oxide signaling. These functional changes were associated with an increase in the maximum binding efficacy of guanosine-5′-O-(3-[ 35 S]thiotriphosphate) ([ 35 S]GTPγS) stimulated by the CB 1 receptor agonist CP 55,940, and a significant decrease in receptor basal activation in the TRPV1-/- hippocampus. Finally, TRPV1-/- hippocampal synaptosomes showed an augmented level of the guanine nucleotide-binding (G) Gα i1 , Gα i2 , and Gα i3 protein alpha subunits. Altogether, the lack of TRPV1 modifies CB 1 receptor signaling in the dentate gyrus and causes the shift from CB 1 receptor-mediated LTD to LTP at the MPP–GC synapses.