Functional mapping of GABA(B)-receptor subtypes in the thalamus.
The thalamus plays an important role in attention mechanisms and the generation of brain rhythms. gamma-Aminobutyric acid type B (GABA(B)) receptors are known to regulate the main output neurons of the thalamus, the thalamocortical relay (TCR) cells. However, the contributions of the two predominant GABA(B)-receptor subtypes, GABA(B(1a,2)) and GABA(B(1b,2)), to the control of TCR cell activity are unknown. Here, we used genetic and electrophysiological methods to investigate subtype-specific GABA(B) effects at the inputs to TCR cells. We found that mainly GABA(B(1a,2)) receptors inhibit the release of glutamate from corticothalamic fibers impinging onto TCR cells. In contrast, both GABA(B(1a,2)) and GABA(B(1b,2)) receptors efficiently inhibit the release of GABA from thalamic reticular nucleus (TRN) neurons onto TCR neurons. Likewise, both GABA(B(1a,2)) and GABA(B(1b,2)) receptors efficiently activate somatodendritic K(+) currents in TCR cells. In summary, our data show that GABA(B(1b,2)) receptors cannot compensate for the absence of GABA(B(1a,2)) receptors at glutamatergic inputs to TCR cells. This shows that the predominant association of GABA(B(1a,2)) receptors with glutamatergic terminals is a feature that is preserved at several brain synapses. Furthermore, our data indicate that the cognitive deficits observed with mice lacking GABA(B(1a,2)) receptors could to some extent relate to attention deficits caused by disinhibited release of glutamate onto TCR neurons.
Ulrich
Daniel
D
Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Basel, Switzerland. ulrichd@tcd.ie
Besseyrias
Valérie
V
Bettler
Bernhard
B
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010721:Phosphinic Acids / Q000494:pharmacology; D018080:Receptors, GABA-B / Q000235:genetics / Q000502:physiology*; D013788:Thalamus / Q000166:cytology / Q000502:physiology*
D001596:Benzylamines; D018755:GABA Agonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D018080:Receptors, GABA-B; C083008:CGP 52432; D001418:Baclofen