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The Journal of Neuroscience, February 15, 2006, 26(7):1906-1912; doi:10.1523/JNEUROSCI.4430-05.2006
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Cellular/Molecular
Alcohol Potently Modulates Climbing FiberPurkinje Neuron Synapses: Role of Metabotropic Glutamate Receptors
Mario Carta, * Manuel Mameli, * andC. Fernando Valenzuela Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131
Correspondence should be addressed to Dr. C. Fernando Valenzuela, Department of Neurosciences, MSC08 4740, 1 University of New Mexico, Albuquerque, NM 87131-0001. Email: fvalenzuela{at}salud.unm.edu
Consumption of alcoholic beverages produces alterations in motor coordination and equilibrium that are responsible for millions of accidental deaths. Studies indicate that ethanol produces these alterations by affecting the cerebellum, a brain region involved in the control of motor systems. Purkinje neurons of the cerebellar cortex have been shown to be particularly important targets of ethanol. However, its mechanism of action at these neurons is poorly understood. We hypothesized that ethanol could modulate Purkinje neuron function by altering the excitatory input provided by the climbing fiber from the inferior olive, which evokes a powerful all-or-none response denoted as the complex spike. To test this hypothesis, we performed whole-cell patch-clamp electrophysiological and Ca2+ imaging experiments in acute slices from rat cerebella. We found that ethanol potently inhibits the late phase of the complex spike and that this effect is the result of inhibition of type-1 metabotropic glutamate receptor-dependent responses at the postsynaptic level. Moreover, ethanol inhibited climbing fiber long-term depression, a form of synaptic plasticity that also depends on activation of these metabotropic receptors. Our findings identify the climbing fiber
Purkinje neuron synapse as an important target of ethanol in the cerebellar cortex and indicate that ethanol significantly affects cerebellar circuits even at concentrations as low as 10 mM (legal blood alcohol level in the United States is below 0.08 g/dl = 17 mM).
Key words: cerebellum; electrophysiology; slice; glutamate; motor; ethanol
Received Oct. 17, 2005; revised Jan. 4, 2006; accepted Jan. 9, 2006.
Correspondence should be addressed to Dr. C. Fernando Valenzuela, Department of Neurosciences, MSC08 4740, 1 University of New Mexico, Albuquerque, NM 87131-0001. Email: fvalenzuela{at}salud.unm.edu
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