GABA B receptor activation changes membrane and ¢lter properties of auditory thalamic neurons Frank Tennigkeit a;b , Dietrich W.F. Schwarz b , Ernest Puil a ; * a Department of Pharmacology and Therapeutics, and The Rotary Hearing Centre, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, B.C. V6T 1Z3, Canada b Department of Surgery, Faculty of Medicine, The University of British Columbia, 221 Wesbrook Mall, Vancouver, B.C. V6T 2B5, Canada Received 19 December 1997; revised 13 April 1998; accepted 21 April 1998 Abstract Inhibitory inputs from nucleus reticularis thalami and the inferior colliculus activate Q-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 Cd 2 , baclofen activated an inwardly rectifying outward K  current, that was sensitive to blockade with Ba 2 (0.5 mM). Intracellular applications of GTPQS occluded the baclofen current whereas similar applications of GDPLS 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 V1 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. z 1998 Elsevier Science B.V. All rights reserved. Key words: Auditory thalamus ; Baclofen ; Q-Aminobutyric acid B ; Resonance 1. Introduction The ventral partition of the medial geniculate body (MGBv) in the rat receives an inhibitory synaptic input from the inferior colliculus (Peruzzi et al., 1997) in ad- dition to feedback from the thalamic reticular nucleus (Shosaku and Sumitomo, 1983). In both instances, Q- aminobutyric acid (GABA) mediates the postsynaptic inhibition. A small number of GABAergic interneurons in the ventral partition ( 6 1%; Winer and Larue, 1988) may contribute to this inhibition in the MGB. Depend- ing on the pattern of activity in these inputs (Kim et al., 1997), a combination of fast inhibitory postsynaptic potentials (IPSPs) mediated by GABA A receptors and slow IPSPs mediated by GABA B receptors produces a long-lasting inhibition of auditory transmission in thal- amocortical neurons. A striking feature of the MGB is the strong expres- sion of GABA B receptors (Kaupmann et al., 1997) which have been implicated in the generation of oscil- latory activity in thalamocortical neurons (Ulrich and Huguenard, 1996b). After blockade of GABA A recep- tors with bicuculline, for example, postsynaptic 0378-5955 / 98 / $19.00 ß 1998 Elsevier Science B.V. All rights reserved. PII:S0378-5955(98)00083-5 * Corresponding author. Tel.: +1 (604) 822-5080; Fax: +1 (604) 822-6980. Hearing Research 122 (1998) 18^24