Cerebellar circuits: Biochemistry, neurotransmitters and neuromodulators: Cannabinoids as modulators in the cerebellum

Abstract

Cannabinoid CB 1 receptors (CB 1 Rs) are the most widespread G-proteincoupled receptors (GPCRs) in the mammalian CNS. CB 1 Rs are present on inhibitory and excitatory presynaptic terminals supplying Purkinje cells (PCs), the sole output of the cerebellar cortex, where CB 1 R activation suppresses transmitter release. CB 1 Rs are part of the endocannabinoid (eCB) system, activated by the lipid mediator 2-arachidonoyl glycerol (2-AG) via retrograde transmission within the cerebellum. CB 1 Rs also mediate synaptic plasticities to modulate cerebellar learning. This review will discuss the latest knowledge regarding CB 1 R circuitry and signalling and their potential modulation.