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.

Peng K; Wang X; Wang Y; Li D; Huang H; Lu Y

The Journal of Neuroscience : The Official Journal of the Society for Neuroscience

2020

2020-08-12

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 Na(V) channels (tetrodotoxin, 1 μM), persistent Na(+) current (I(NaP)) (Riluzole, 10 μM), or Ca(V) channels (CdCl(2), 100 µM). Presynaptic calyx recordings revealed that 3,5-DHPG shifted the activation of I(NaP) to more hyperpolarized voltages and increased I(NaP) at resting membrane potential. Our data indicate that mGluR I enhance spontaneous glutamate release via regulation of I(NaP) and subsequent Ca(2+)-dependent processes under rest condition.SIGNIFICANCE STATEMENTFor brain cells to communicate with each other, neurons release chemical messengers, termed neurotransmitters, in response to action potential invasion (evoked release). Neurons also release neurotransmitters spontaneously. Recent works have revealed different release machineries underlying these two release modes, and their different roles in synaptic development and plasticity. Our recent work discovered differential neuromodulation of these two release modes, but the mechanisms are not well understood. The present study showed that activation of group I metabotropic glutamate receptors enhanced spontaneous glutamate release in an auditory brainstem nucleus, while suppressing evoked release. The modulation is dependent on a persistent Na(+) current and involves subsequent Ca(2+) signaling, providing insight into the mechanisms underlying the different release modes in auditory processing.

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1529-2401 0270-6474

NEOMED College of Medicine

NEOMED Postdoc Publications

Department of Anatomy & Neurobiology

August 2020 List