Endocannabinoid long-term depression revealed at medial perforant path excitatory synapses in the dentate gyrus

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

“…The present results also show a CB 1 receptor-dependent shift to MPP-LTP in TRPV1-/-(Figure 5) after applying the LFS that elicits MPP-LTD under normal conditions (Peñasco et al, 2019;Fontaine et al, 2020). Interestingly, this type of potentiation is independent of NMDAR signaling, although eCB-eLTD requires NMDA receptor activation at other synapses (Sjöström et al, 2003;Bender et al, 2006;Lutzu and Castillo, 2021).…”

“…TRPV1 also localizes to the post-synaptic sites of excitatory and inhibitory synaptic terminals in the molecular layer (ML) of the dentate gyrus where it plays a key role in the synaptic transmission and plasticity (Chávez et al, 2010;Chavez et al, 2014;Canduela et al, 2015;Puente et al, 2015). Thereby, like in other brain regions (Lafourcade et al, 2007;Grueter et al, 2010;Puente et al, 2011), long-term depression (LTD) at medial perforant path (MPP) synapses is mediated by post-synaptic TRPV1 activity (Chávez et al, 2010) and CB 1 receptor signaling (Peñasco et al, 2019;Fontaine et al, 2020). Conversely, high-frequency stimulation (HFS) of the lateral perforant path (LPP) triggers a CB 1 receptor-dependent longterm potentiation (LTP) that requires post-synaptic N-methyl-D -aspartate (NMDA) receptors, metabotropic glutamate receptor 5 (mGluR5), and mobilization of the endocannabinoid 2arachidonoylglycerol (2-AG) (Wang et al, 2016).…”

Deletion of the cannabinoid CB1 receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses

“…The G protein‐coupled cannabinoid type‐1 (CB 1 ) receptor serves many functions in the brain as a result of its broad distribution throughout it (Busquets‐Garcia, Bains, & Marsicano, ; Gutiérrez‐Rodríguez et al, ; Hu & Mackie, ; Kano, Ohno‐Shosaku, Hashimotodani, Uchigashima, & Watanabe, ; Katona & Freund, ; Monday & Castillo, ; Tsou, Brown, Sañudo‐Peña, Mackie, & Walker, ). The development of animal models with CB 1 receptors genetically manipulated at specific cell phenotypes and organelles (i.e., glutamatergic, GABAergic, cholinergic neurons, astrocytes, and mitochondria) have greatly helped to decipher accurately the CB 1 receptor localization at specific cell compartments where it has particular roles modulating brain pathways activity and, ultimately, endocannabinoid‐dependent brain functions and behaviors that turn altered in pathological brain conditions (Bellocchio et al, ; Bonilla‐Del Rίo et al, ; Gutiérrez‐Rodríguez et al, ; Hebert‐Chatelain et al, ; Katona & Freund, ; Lutz, Marsicano, Maldonado, & Hillard, ; Marsicano et al, ; Marsicano & Kuner, ; Martín‐García et al, ; Monday, Younts, & Castillo, ; Monory et al, ; Peñasco et al, ; Puente et al, ; Soria‐Gómez et al, ). Interesting is the observation that mice with the global lack of CB 1 receptors do not show drastic changes neither at the cellular/phenotypic level (Mulder et al, ) nor in motor coordination (Bilkei‐Gorzo et al, ; Kishimoto & Kano, ), despite the fact that CB 1 receptors have important functions during development (Aguado et al, ; Berghuis et al, , ; de Salas‐Quiroga et al, ; Fernández‐Ruiz, Berrendero, Hernández, & Ramos, ; Gaffuri, Ladarre, & Lenkei, ; Keimpema, Mackie, & Harkany, ; Williams, Walsh, & Doherty, ; Zhou et al, ) and are highly expressed in brain regions involved in motor control, including the cerebellum (Gutiérrez‐Rodríguez et al, ; Kawamura et al, ; Manzanares et al, ; Tsou et al, ).…”

Cannabinoid Control of Olfactory Processes: The Where Matters

“…In neurons, the main effect of CB1 receptor activation is a decrease in neurotransmitter release, inducing different forms of endocannabinoid-mediated plasticity [3], such as the depolarization-induced suppression of inhibition/excitation (DSI/DSE; [7][8][9]), or the long-term depression of inhibitory/ excitatory synapses [10][11][12][13][14]. CB1 receptors are widely expressed in the central nervous system and likely represent the most abundant GPCR in the brain [15].…”