Ethanol acutely modulates mGluR1-dependent long-term depression in cerebellum.
BACKGROUND
Acute and chronic ethanol exposure produces profound impairments in motor functioning. Individuals with lower sensitivity to the acute motor impairing effects of ethanol have an increased risk of developing alcohol dependence and abuse, and infants with subtle delays in motor coordination development may have an increased risk for subsequently developing alcoholism. Thus, understanding the mechanism by which ethanol disrupts motor functioning is very important.


METHODS
Parasagittal slices of the cerebellar vermis (250 microM thick) were prepared from P17 to 20 Sprague-Dawley rats. Whole-cell recordings of Purkinje cells were obtained with an Axopatch 200B amplifier. Parallel fiber-Purkinje cell synaptic currents were sampled at 1 kHz and digitized at 10 kHz, and synaptic long-term depression (LTD) was observed in either external or internal application of ethanol for comparison.


RESULTS
We determined whether ethanol acutely affects parallel fiber LTD using whole-cell patch-clamp recordings from Purkinje cells. Application of ethanol both externally (50 mM) and internally (17 and 10 mM) significantly suppressed mGluR-mediate slow currents. Short-term external ethanol exposure (50 but not 17 mM) during tetanus blocked mGluR-dependent parallel fiber LTD. Furthermore, internal 17 and 10 mM ethanol completely inhibited this LTD.


CONCLUSIONS
The results of the current study demonstrate that ethanol acutely suppresses parallel fiber LTD and may influence the mGluR-mediated slow current intracellularly. This study, plus previous evidence by Carta and colleagues (2006) and Belmeguenai and colleagues (2008), suggests significant actions of ethanol on mGluR-mediated currents and its dependent plasticity in brain.
Su
Li-Da
LD
Department of Neurobiology/Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, China.
Sun
Cheng-Long
CL
Shen
Ying
Y
D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D036881:Long-Term Synaptic Depression / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013997:Time Factors
D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D000431:Ethanol