Cerebellar Circuits: Biochemistry, Neurotransmitters and Neuromodulators
Cannabinoid CB1 receptors (CB1Rs) are the most widespread G-protein-coupled receptors (GPCRs) in the mammalian CNS. CB1Rs are present on inhibitory and excitatory presynaptic terminals supplying Purkinje cells (PCs), the sole output of the cerebellar cortex, where CB1R activation suppresses transmitter release. CB1Rs are part of the endocannabinoid (eCB) system, activated by the lipid mediator 2-arachidonoyl glycerol (2-AG) via retrograde transmission within the cerebellum. CB1Rs also mediate synaptic plasticities to modulate cerebellar learning. This review will discuss the latest knowledge regarding CB1R circuitry and signalling and their potential modulation.
KeywordsCB1 receptor Endocannabinoid Purkinje cells
- Hoffman AF, Lupica CR (2013) Synaptic targets of Δ9-tetrahydrocannabinol in the central nervous system. Cold Spring Harb Perspect Med 3 pii: a012237.Google Scholar
- Ohno-Shosaku T, Kano M (2014) Endocannabinoid-mediated retrograde modulation of synaptic transmission. Curr Opin Neurobiol 29:1–8
- Stephens GJ (2016) Does modulation of the endocannabinoid system have potential therapeutic utility in cerebellar ataxia? J Physiol [Epub ahead of print Mar 11]Google Scholar
- Yoshida T, Fukaya M, Uchigashima M et al (2006) Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor. J Neurosci 26:4740–4751CrossRefPubMedGoogle Scholar