Receptores mGlu-I no MNTB modulam canais HCN e regulam a liberação de vesículas sinápticas

Abstract

We examined effects of Group I metabotropic glutamate receptors on the excitability of principal neurons in mouse medial nucleus of the trapezoid body (MNTB). These effects were evaluated when the receptors were activated with an exogenous agonist or by synaptically released endogenous glutamate. Under voltage‐clamp the selective agonist, S‐3,5‐dihydroxyphenylglycine (DHPG) evoked an inward current, referred to as ImGlu-I, which was developmentally stable from shortly after birth (P8) through nine months old. ImGlu-I had low temperature dependence in the range 25–34°C, consistent with a channel mechanism. Under current-clamp recording mGlu-I receptors activation with DHPG causes membrane depolarization with decrease in the membrane conductance and increase in the depolarizing sag. The sag was dependent on HCN channels. Voltage-clamp measurements of Ih indicated a small (6%) increase in Gmax by DHPG with no change in the voltage dependence; this suggests that HCN channels contribute partially to the increase in the excitability by Group I mGlu receptors. Application of mGlu-I receptor antagonists indicated that mGlu receptors are tonically active and are sensitive to elevations in ambient glutamate by the glutamate reuptake blocker threo-β-benzyloxyaspartic acid (DL-TBOA). Even without the use of TBOA, during high frequency stimulation of the calyx of Held application of mGlu-I receptor inhibitors caused postsynaptic membrane hyperpolarizes and increased the amplitude of EPSP through mechanisms related to Pr and quantal content. Thus, activation of Group I mGlu receptors modifies the excitability of MNTB neurons and contributes to the reliability of high frequency firing in this auditory relay nucleus through both pre- and post- synaptic mechanisms.