Alcohol potently modulates climbing fiber→purkinje neuron synapses: Role of metabotropic glutamate receptors
Journal of Neuroscience. 2006-02-15; 26(7): 1906-1912
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1. J Neurosci. 2006 Feb 15;26(7):1906-12.
Alcohol potently modulates climbing fiber–>Purkinje neuron synapses: role of
metabotropic glutamate receptors.
Carta M(1), Mameli M, Valenzuela CF.
(1)Department of Neurosciences, University of New Mexico Health Sciences Center,
Albuquerque, New Mexico 87131, USA.
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).
PMID: 16481422 [Indexed for MEDLINE]