Gamma-aminobutyric acid(B) autoreceptors in substantia nigra and neostriatum of the weaver mutant mouse.
The weaver mutation causes cell loss in the center of the substantia nigra, pars compacta. We compared the depression of gamma-aminobutyric acid (GABA)(A) synaptic currents by the GABA(B) agonist R-baclofen in pars compacta neurons of weaver mice which were largely spared from cell degeneration and of wild-type mice. In weaver neurons the suppression of GABA(A) synaptic currents by R-baclofen was reduced compared to wild-type neurons. The EC(50) of R-baclofen was 6.3 times higher in weaver than in wild-type mice. In the neostriatum, which is not a target of the mutation, such a difference did not exist. We conclude that in the pars compacta the weaver mutation leads to a reduced presynaptic autoinhibition through GABA(B) receptors which may promote survival of a subset of weaver neurons in the pars compacta.
Radnikow
G
G
Institut für Physiologie und Pathophysiologie, Universität Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany.
Titz
S
S
Mades
S
S
Bäurle
J
J
Misgeld
U
U
D000818:Animals; D017660:Autoreceptors / Q000187:drug effects / Q000378:metabolism*; D001418:Baclofen / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists; D020271:Heredodegenerative Disorders, Nervous System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*
D017660:Autoreceptors; D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D017470:Receptors, Glutamate; D001418:Baclofen; D004298:Dopamine