Alcohol impairs long-term depression at the cerebellar parallel fiber-Purkinje cell synapse

Amor Belmeguenai, Paolo Botta, John T. Weber, Mario Carta, Martijn De Ruiter, Chris I. De Zeeuw, C. Fernando Valenzuela, Christian Hansel
Journal of Neurophysiology. 2008-12-01; 100(6): 3167-3174
DOI: 10.1152/jn.90384.2008

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1. J Neurophysiol. 2008 Dec;100(6):3167-74. doi: 10.1152/jn.90384.2008. Epub 2008
Oct 15.

Alcohol impairs long-term depression at the cerebellar parallel fiber-Purkinje
cell synapse.

Belmeguenai A(1), Botta P, Weber JT, Carta M, De Ruiter M, De Zeeuw CI,
Valenzuela CF, Hansel C.

Author information:
(1)Department of Neuroscience, Erasmus University Medical Center, Rotterdam, The

Acute alcohol consumption causes deficits in motor coordination and gait,
suggesting an involvement of cerebellar circuits, which play a role in the fine
adjustment of movements and in motor learning. It has previously been shown that
ethanol modulates inhibitory transmission in the cerebellum and affects synaptic
transmission and plasticity at excitatory climbing fiber (CF) to Purkinje cell
synapses. However, it has not been examined thus far how acute ethanol
application affects long-term depression (LTD) and long-term potentiation (LTP)
at excitatory parallel fiber (PF) to Purkinje cell synapses, which are assumed to
mediate forms of cerebellar motor learning. To examine ethanol effects on PF
synaptic transmission and plasticity, we performed whole cell patch-clamp
recordings from Purkinje cells in rat cerebellar slices. We found that ethanol
(50 mM) selectively blocked PF-LTD induction, whereas it did not change the
amplitude of excitatory postsynaptic currents at PF synapses. In contrast,
ethanol application reduced voltage-gated calcium currents and type 1
metabotropic glutamate receptor (mGluR1)-dependent responses in Purkinje cells,
both of which are involved in PF-LTD induction. The selectivity of these effects
is emphasized by the observation that ethanol did not impair PF-LTP and that
PF-LTP could readily be induced in the presence of the group I mGluR antagonist
AIDA or the mGluR1a antagonist LY367385. Taken together, these findings identify
calcium currents and mGluR1-dependent signaling pathways as potential ethanol
targets and suggest that an ethanol-induced blockade of PF-LTD could contribute
to the motor coordination deficits resulting from alcohol consumption.

DOI: 10.1152/jn.90384.2008
PMCID: PMC2604851
PMID: 18922952 [Indexed for MEDLINE]

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