Presynaptic CB1 receptors regulate synaptic plasticity at cerebellar parallel fiber synapses

• Published in: Journal of neurophysiology Vol. 105; no. 2; pp. 958 - 963
• Main Authors: Carey, Megan R, Myoga, Michael H, McDaniels, Kimberly R, Marsicano, Giovanni, Lutz, Beat, Mackie, Ken, Regehr, Wade G
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.02.2011
• Subjects: Animals; Cerebellum - physiology; Long-Term Synaptic Depression - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuronal Plasticity - physiology; Presynaptic Terminals - physiology; Receptor, Cannabinoid, CB1 - metabolism; Synaptic Transmission - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00980.2010

Endocannabinoids are potent regulators of synaptic strength. They are generally thought to modify neurotransmitter release through retrograde activation of presynaptic type 1 cannabinoid receptors (CB1Rs). In the cerebellar cortex, CB1Rs regulate several forms of synaptic plasticity at synapses onto Purkinje cells, including presynaptically expressed short-term plasticity and, somewhat paradoxically, a postsynaptic form of long-term depression (LTD). Here we have generated mice in which CB1Rs were selectively eliminated from cerebellar granule cells, whose axons form parallel fibers. We find that in these mice, endocannabinoid-dependent short-term plasticity is eliminated at parallel fiber, but not inhibitory interneuron, synapses onto Purkinje cells. Further, parallel fiber LTD is not observed in these mice, indicating that presynaptic CB1Rs regulate long-term plasticity at this synapse.