Retrograde endocannabinoid signaling in the cerebellar cortex.

The regulation of Purkinje cell activity is important for motor behavior and motor learning. As the sole output cell of the cerebellar cortex, Purkinje cell firing is controlled by parallel fibers and climbing fiber synapses, and by inhibitory interneurons. Depolarization of Purkinje cells evokes endocannabinoid release that activates cannabinoid CB1 receptors expressed on boutons of its synaptic inputs to transiently decrease neurotransmitter release. In addition, associative activation of the excitatory inputs can liberate endocannabinoids to decrease synaptic strength for a prolonged duration. Here we review the different mechanisms of evoking endocannabinoid release and discuss the physiological role of endocannabinoids in mediating global modulation of synaptic strength, localized short-term associative plasticity and cerebellar long term depression.