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The Journal of Neuroscience, August 9, 2006, 26(32):8289-8294; doi:10.1523/JNEUROSCI.0805-06.2006
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Brief Communications
Climbing Fiber-Evoked Endocannabinoid Signaling Heterosynaptically Suppresses Presynaptic Cerebellar Long-Term Potentiation
Boeke J. van Beugen, * Raghavendra Y. Nagaraja, * andChristian Hansel Department of Neuroscience, Erasmus University Medical Center, 3000 DR Rotterdam, The Netherlands
Correspondence should be addressed to Christian Hansel, Department of Neuroscience, Erasmus University Medical Center, Dr. Molewaterplein 50, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Email: c.hansel{at}erasmusmc.nl
Endocannabinoid signaling has been demonstrated to mediate depolarization-induced suppression of excitation at climbing fiber (CF) and parallel fiber (PF) synapses onto cerebellar Purkinje cells. Here, we show that CF-evoked release of cannabinoids (CBs) additionally suppresses a presynaptic form of long-term potentiation (LTP) at PF synapses. PF-LTP can be induced by 8 Hz PF tetanization but is blocked when the PF tetanization is paired with 4 or 1 Hz CF coactivation. CF activity can be substituted for by bath application of the CB receptor agonist WIN55,212-2 [R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone]. In the presence of the CB1 receptor antagonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide], CF activity no longer suppresses PF-LTP. Presynaptic potentiation can also be obtained by the adenylyl cyclase activator forskolin. WIN55,212-2 blocked this forskolin-mediated enhancement, showing that CB1 receptor activation interferes with the adenylyl cyclase–protein kinase A cascade, which participates in LTP induction. CF activity has been described to promote the induction of postsynaptic PF-long-term depression (LTD) and to impair postsynaptic PF-LTP. Our observation that CF activity blocks the induction of presynaptic LTP suggests that the CF input controls all forms of presynaptic and postsynaptic PF plasticity and that CF activity provides a "safety lock" to prevent an enhancement of transmitter release while postsynaptic AMPA receptor function is downregulated during LTD.
Key words: cannabinoids; cerebellum; long-term depression; long-term potentiation; parallel fiber; Purkinje cell
Received Feb. 22, 2006; revised June 28, 2006; accepted June 29, 2006.
Correspondence should be addressed to Christian Hansel, Department of Neuroscience, Erasmus University Medical Center, Dr. Molewaterplein 50, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Email: c.hansel{at}erasmusmc.nl
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