Mechanisms and functional impact of Group I metabotropic glutamate receptor modulation of excitability in mouse MNTB neurons

We examined effects of Group I metabotropic glutamate receptors on the excitability of mouse medial nucleus of the trapezoid body (MNTB) neurons. The selective agonist, S-3,5-dihydroxyphenylglycine (DHPG), evoked a dose-dependent depolarization of the resting potential, increased membrane resistance, increased sag depolarization, and promoted rebound action potential firing. Under voltage-clamp, DHPG evoked an inward current, referred to as I_DHPG, which was developmentally stable through postnatal day P56. I_DHPG had low temperature dependence in the range 25–34°C, consistent with a channel mechanism. However, the I-V relationship took the form of an inverted U that did not reverse at the calculated Nernst potential for K⁺ or Cl⁻. Thus, it is likely that more than one ion type contributes to I_DHPG and the mix may be voltage dependent. I_DHPG was resistant to the Na⁺ channel blockers tetrodotoxin and amiloride, and to inhibitors of iGluR (CNQX and MK801). I_DHPG was inhibited 21% by Ba²⁺ (500 μM), 60% by ZD7288 (100 μM) and 73% when the two antagonists were applied together, suggesting that KIR channels and HCN channels contribute to the current. Voltage clamp measurements of I_H indicated a small (6%) increase in G_max by DHPG with no change in the voltage dependence. DHPG reduced action potential rheobase and reduced the number of post-synaptic AP failures during high frequency stimulation of the calyx of Held. Thus, activation of post-synaptic Group I mGlu receptors modifies the excitability of MNTB neurons and contributes to the reliability of high frequency firing in this auditory relay nucleus.