Functional Mapping of GABAB-Receptor Subtypes in the Thalamus

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Abstract
The thalamus plays an important role in attention mechanisms and the generation of brain rhythms. γ-Aminobutyric acid type B (GABAB) receptors are known to regulate the main output neurons of the thalamus, the thalamocortical relay (TCR) cells. However, the contributions of the two predominant GABAB-receptor subtypes, GABAB(1a,2) and GABAB(1b,2), to the control of TCR cell activity are unknown. Here, we used genetic and electrophysiological methods to investigate subtype-specific GABAB effects at the inputs to TCR cells. We found that mainly GABAB(1a,2) receptors inhibit the release of glutamate from corticothalamic fibers impinging onto TCR cells. In contrast, both GABAB(1a,2) and GABAB(1b,2) receptors efficiently inhibit the release of GABA from thalamic reticular nucleus (TRN) neurons onto TCR neurons. Likewise, both GABAB(1a,2) and GABAB(1b,2) receptors efficiently activate somatodendritic K+ currents in TCR cells. In summary, our data show that GABAB(1b,2) receptors cannot compensate for the absence of GABAB(1a,2) receptors at glutamatergic inputs to TCR cells. This shows that the predominant association of GABAB(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 GABAB(1a,2) receptors could to some extent relate to attention deficits caused by disinhibited release of glutamate onto TCR neurons.