Effects of metabotropic glutamate receptor activation in auditory thalamus

Metabotropic glutamate receptors (mGluRs) are expressed predominantly in de ndritic regions of neurons of auditory thalamus. We studied the effects of mGluR activation in neurons of the ventral partition of medial geniculate b ody (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 mu M), depolarized MGBv neurons (n = 67), changing evoked response patterns from bursts to tonic firing as wel l as frequency responses from resonance (similar to 1 Hz) to low-pass filte r characteristics. The depolarization was resistant to Nai-channel blockade with tetrodotoxin (TTX; 300 nM) and Ca2+-channel blockade with Cd2+ (0.1 m M). The application of 1S,3R-ACPD did not change input conductance and prod uced an inward current (I-ACPD) with an average amplitude of 84.2 +/- 5.3 p A (at -70 mV, it = 22). The application of the mGluR antagonist, (RS)-alpha -methyl-3-carboxyphenylglycine (0.5 mM), reversibly blocked the depolarizat ion or I-ACPD. During intracellular application of guanosine 5'-O-(3-thiotr iphosphate) from the recording electrode, bath application of 1S,3R-ACPD ir reversibly activated a large amplitude I-ACPD. During intracellular applica tion of guanosine 5'-O-(2-thiodiphosphate), application of 1S,3R-ACPD evoke d only a small I-ACPD. These results implicate G proteins in mediation of t he 1S,3R-ACPD response. A reduction of external [Na+] from 150 to 26 mM dec reased 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 n ot 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 -8 5 mV, IS,3R-ACPD application reversibly attenuated an inward rectification, displayed by 11 of 20 neurons. Blockade of an inwardly rectifying K+ curre nt 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 whi ch Cs+ blocked; this unmasked a voltage dependence of the inward I-ACPD wit h a maximum amplitude at similar to-30 mV. The I-ACPD properties are consis tent with mGluR expression as a mt-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 inhib ition of the inward rectifier, I-KIR. These mechanisms differ from previous ly reported mGluR effects in the thalamus.