Imperial College London

Prof. William Wisden F. Med. Sci.

Faculty of Natural SciencesDepartment of Life Sciences

Chair in Molecular Neuroscience
 
 
 
//

Contact

 

+44 (0)20 7594 9744w.wisden Website CV

 
 
//

Location

 

401BSir Ernst Chain BuildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Korpi:1999,
author = {Korpi, ER and Koikkalainen, P and Vekovischeva, OY and Makela, R and Kleinz, R and Uusi-Oukari, M and Wisden, W},
journal = {Eur J Neurosci},
pages = {233--240},
title = {Cerebellar granule-cell-specific GABA-A receptors attenuate benzodiazepine-induced ataxia: evidence from alpha 6-subunit-deficient mice},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9987027},
volume = {11},
year = {1999}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Benzodiazepine- and alcohol-induced ataxias in rodents have been proposed to be affected by the gamma-aminobutyric acid type A (GABAA) receptor alpha 6 subunit, which contributes to receptors specifically expressed in cerebellar granule cells. We have studied an alpha 6 -/- mouse line for motor performance and drug sensitivity. These mice, as a result of a specific genetic lesion, carry a precise impairment at their Golgi-granule cell synapses. On motor performance tests (rotarod, horizontal wire, pole descending, staircase and swimming tests) there were no robust baseline differences in motor function or motor learning between alpha 6 -/- and alpha 6 +/+ mice. On the rotarod test, however, the mutant mice were significantly more impaired by diazepam (5-20 mg/kg, i.p.), when compared with alpha 6 +/+ control and background C57BL/6J and 129/SvJ mouse lines. Ethanol (2.0-2.5 g/kg, i.p.) produced similar impairment in the alpha 6 -/- and alpha +/+ mice. Diazepam-induced ataxia in alpha 6 -/- mice could be reversed by the benzodiazepine site antagonist flumazenil, indicating the involvement of the remaining alpha 1 beta 2/3 gamma 2 GABAA receptors of the granule cells. The level of activity in this synapse is crucial in regulating the execution of motor tasks. We conclude that GABAA receptor alpha 6 subunit-dependent actions in the cerebellar cortex can be compensated by other receptor subtypes; but if not for the alpha 6 subunit, patients on benzodiazepine medication would suffer considerably from ataxic side-effects.
AU - Korpi,ER
AU - Koikkalainen,P
AU - Vekovischeva,OY
AU - Makela,R
AU - Kleinz,R
AU - Uusi-Oukari,M
AU - Wisden,W
EP - 240
PY - 1999///
SN - 0953-816X
SP - 233
TI - Cerebellar granule-cell-specific GABA-A receptors attenuate benzodiazepine-induced ataxia: evidence from alpha 6-subunit-deficient mice
T2 - Eur J Neurosci
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9987027
VL - 11
ER -