Mechanisms underlying enhancement of spontaneous glutamate release by group I mGluRs at a central auditory synapse

Mechanisms underlying enhancement of spontaneous glutamate release by group I mGluRs at a central auditory synapse

Kang P;Wang X;Yuan W;Dainan L;Hai H;Yong L

Journal Of Neuroscience

2020

2020-09-09

One emerging concept in neuroscience states that synaptic vesicles and the molecular machinery underlying spontaneous transmitter release are different from those underlying action potential-driven synchronized transmitter release. Differential neuromodulation of these two distinct release modes by metabotropic glutamate receptors (mGluRs) constitutes critical supporting evidence. However, the mechanisms underlying such a differential modulation are not understood. Here, we investigated the mechanisms of the modulation by group I mGluRs (mGluR I) on spontaneous glutamate release in the medial nucleus of the trapezoid body (MNTB), an auditory brainstem nucleus critically involved in sound localization. Whole-cell patch recordings from brainstem slices of mice of both sexes were performed. Activation of mGluR I by 3,5-DHPG (200 μM) produced an inward current at -60 mV, and increased spontaneous glutamate release in MNTB neurons. Pharmacological evidence indicated involvement of both mGluR1 and mGluR5, which was further supported for mGluR5 by immunolabeling results. The modulation was eliminated by blocking NaV channels (tetrodotoxin, 1 μM), persistent Na+ current (INaP) (Riluzole, 10 μM), or CaV channels (CdCl2, 100 µM). Presynaptic calyx recordings revealed that 3,5-DHPG shifted the activation of INaP to more hyperpolarized voltages and increased INaP at resting membrane potential. Our data indicate that mGluR I enhance spontaneous glutamate release via regulation of INaP and subsequent Ca2+-dependent processes under rest condition. [ABSTRACT FROM AUTHOR]

SYNAPTIC vesicles; auditory; mGluR; MNTB; EPSC; spontaneous glutamate release; voltage-gated sodium channel; DIRECTIONAL hearing; GLUTAMIC acid; MEMBRANE potential; SYNAPSES

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journalArticle

7027-7042

37

40

2706474

NEOMED College of Medicine Postdoc

NEOMED Postdoc Publications

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