Mechanisms underlying enhancement of spontaneous glutamate release by group I mGluRs at a central auditory synapse
SYNAPTIC vesicles; auditory; mGluR; MNTB; EPSC; spontaneous glutamate release; voltage-gated sodium channel; DIRECTIONAL hearing; GLUTAMIC acid; MEMBRANE potential; SYNAPSES
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]
Kang P;Wang X;Yuan W;Dainan L;Hai H;Yong L
Journal Of Neuroscience
2020
2020-09-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/" target="_blank" rel="noreferrer noopener"></a>
Activity-dependent synaptic integration and modulation of bilateral excitatory inputs in an auditory coincidence detection circuit.
EPSC; mGluR; neuromodulation; synaptic integration
KEY POINTS: Binaural excitatory inputs to coincidence detection neurons in nucleus laminaris (NL) play essential roles in interaural time difference coding for sound localization. Here, we show that the two excitatory inputs are physiologically nearly completely segregated. Synaptic integration shows linear summation of EPSPs, ensuring high efficiency of coincidence detection of the bilateral excitatory inputs. We further show that the two excitatory inputs to single NL neurons are symmetrical in synaptic strength, kinetics and short-term plasticity. Modulation of the EPSCs by metabotropic glutamate receptors (mGluRs) is identical between the two excitatory inputs, maintaining balanced bilateral excitation under neuromodulatory conditions. Unilateral hearing deprivation reduces synaptic excitation and paradoxically strengthens mGluR modulation of EPSCs, suggesting activity-dependent anti-homeostatic regulation, a novel synaptic plasticity in response to sensory manipulations. ABSTRACT: Neurons in the avian nucleus laminaris (NL) receive bilateral excitatory inputs from the cochlear nucleus magnocellularis, via morphologically symmetrical dorsal (ipsilateral) and ventral (contralateral) dendrites. Using in vitro whole-cell patch recordings in chicken brainstem slices, we investigated synaptic integration and modulation of the bilateral inputs to NL under normal and hearing deprivation conditions. We found that the two excitatory inputs onto single NL neurons were nearly completely segregated, and integration of the two inputs was linear for EPSPs. The two inputs had similar synaptic strength, kinetics and short-term plasticity. EPSCs in low but not middle and high frequency neurons were suppressed by activation of group I and II metabotropic glutamate receptors (mGluR I and II), with similar modulatory strength between the ipsilateral and contralateral inputs. Unilateral hearing deprivation by cochlea removal reduced the excitatory transmission on the deprived dendritic domain of NL. Interestingly, EPSCs evoked at the deprived domain were modulated more strongly by mGluR II than at the counterpart domain that received intact input in low frequency neurons, suggesting anti-homeostatic regulation. This was supported by a stronger expression of mGluR II protein on the deprived neuropils of NL. Under mGluR II modulation, EPSCs on the deprived input show transient synaptic facilitation, forming a striking contrast with normal hearing conditions under which pure synaptic depression is observed. These results demonstrate physiological symmetry and thus balanced bilateral excitatory inputs to NL neurons. The activity-dependent anti-homeostatic plasticity of mGluR modulation constitutes a novel mechanism regulating synaptic transmission in response to sensory input manipulations.
Lu Yong; Liu Yu-Wei; Curry Rebecca J
The Journal of physiology
2018
2018-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1113/JP275735" target="_blank" rel="noreferrer noopener">10.1113/JP275735</a>