GABA(B) receptor activation changes membrane and filter properties of auditory thalamic neurons

Inhibitory inputs from nucleus reticularis thalami and the inferior colliculus activate gamma-aminobutyric acid B (GABA(B)) receptors in auditory thalamic neurons. These metabotropic receptors have been implicated in the oscillatory behavior of thalamic neurons. We studied the effects of the GABA(B) receptor agonist, baclofen, on membrane and filter properties of neurons in the ventral partition of the medial geniculate body (MGBv) of the rat, using whole-cell patch-clamp recording techniques in a slice preparation. Application of baclofen caused a concentration-dependent and reversible hyperpolarization of MGBv neurons. An increase in membrane conductance shunted voltage signals. The shunt suppressed firing in both tonic and burst modes which normally characterize the neuronal excitation from depolarized and hyperpolarized potentials, respectively. The GABA(B) receptor antagonist, CGP 35348 (0.5 mM), completely and reversibly blocked the baclofen-evoked hyperpolarization and increase in conductance. In voltage-clamp and during blockade of synaptic transmission with tetrodotoxin and Cd2+, baclofen activated an inwardly rectifying outward K+ current, that was sensitive to blockade with Ba2+ (0.5 mM). Intracellular applications of GTPgammaS occluded the baclofen current whereas similar applications of GDPbetaS prevented it, suggesting that G-proteins mediated the baclofen current. We measured the impedance amplitude profile in the frequency domain with swept sinusoidal current injection. MGBv neurons normally have lowpass filter characteristics at depolarized potentials and resonance at approximately 1 Hz at hyperpolarized potentials. Baclofen application reduced the impedance below 20 Hz which lowered the membrane filter quality and abolished the resonance. Despite its hyperpolarizing effect, therefore, baclofen eliminated an intrinsic tendency to oscillate as well as the intrinsic frequency selectivity of MGBv neurons.