The Journal of Neurophysiology Vol. 82 No. 2 August 1999, pp. 718-729
Copyright ©1999 by the American Physiological Society

Effects of Metabotropic Glutamate Receptor Activation in Auditory Thalamus

 ¹Department of Pharmacology and Therapeutics and  ²The Rotary Hearing Centre, Department of Surgery, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada

Tennigkeit, Frank, Dietrich W. F. Schwarz, and Ernest Puil. Effects of Metabotropic Glutamate Receptor Activation in Auditory Thalamus. J. Neurophysiol. 82: 718-729, 1999. Metabotropic glutamate receptors (mGluRs) are expressed predominantly in dendritic regions of neurons of auditory thalamus. We studied the effects of mGluR activation in neurons of the ventral partition of medial geniculate body (MGBv) using whole cell current- and voltage-clamp recordings in brain slices. Bath application of the mGluR-agonist, 1S,3R-1-aminocyclopentan-1,3-dicarboxylic acid or 1S,3R-ACPD (5-100 µM), depolarized MGBv neurons (n = 67), changing evoked response patterns from bursts to tonic firing as well as frequency responses from resonance (~1 Hz) to low-pass filter characteristics. The depolarization was resistant to Na⁺-channel blockade with tetrodotoxin (TTX; 300 nM) and Ca²⁺-channel blockade with Cd²⁺ (0.1 mM). The application of 1S,3R-ACPD did not change input conductance and produced an inward current (I_ACPD) with an average amplitude of 84.2 ± 5.3 pA (at 70 mV, n = 22). The application of the mGluR antagonist, (RS)--methyl-4-carboxyphenylglycine (0.5 mM), reversibly blocked the depolarization or I_ACPD. During intracellular application of guanosine 5'-O-(3-thiotriphosphate) from the recording electrode, bath application of 1S,3R-ACPD irreversibly activated a large amplitude I_ACPD. During intracellular application of guanosine 5'-O-(2-thiodiphosphate), application of 1S,3R-ACPD evoked only a small I_ACPD. These results implicate G proteins in mediation of the 1S,3R-ACPD response. A reduction of external [Na⁺] from 150 to 26 mM decreased I_ACPD to 32.8 ± 10.3% of control. Internal applications of a Ca²⁺ chelator, 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA; 10 mM), suppressed I_ACPD, implying a contribution of a Ca²⁺ signal or Na⁺/Ca²⁺ exchange. However, partial replacement of Na⁺ with Li⁺ (50 mM) did not significantly change I_ACPD. Therefore it seemed less likely that a Na⁺/Ca²⁺ exchange current was a major participant in the response. A reduction of extracellular [K⁺] from 5.25 to 2.5 mM or external Ba²⁺ (0.5 mM) or Cs⁺ (2 mM) did not significantly change I_ACPD between 40 and 85 mV. Below 85 mV, 1S,3R-ACPD application reversibly attenuated an inward rectification, displayed by 11 of 20 neurons. Blockade of an inwardly rectifying K⁺ current with Ba²⁺ (1 mM) or Cs⁺ (2-3 mM) occluded the attenuation. In the range positive to 40 mV, 1S,3R-ACPD application activated an outward current which Cs⁺ blocked; this unmasked a voltage dependence of the inward I_ACPD with a maximum amplitude at ~30 mV. The I_ACPD properties are consistent with mGluR expression as a TTX-resistant, persistent Na⁺ current in the dendritic periphery. We suggest that mGluR activation changes the behavior of MGBv neurons by three mechanisms: activation of a Na⁺-dependent inward current; activation of an outward current in a depolarized range; and inhibition of the inward rectifier, I_KIR. These mechanisms differ from previously reported mGluR effects in the thalamus.