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. 2018:1:001.
doi: 10.24966/TAP-7752/100001. Epub 2018 Feb 9.

Anatomy and Physiology of Metabotropic Glutamate Receptors in Mammalian and Avian Auditory System

Zheng-Quan Tang  1 , Yong Lu  2
Affiliations

Anatomy and Physiology of Metabotropic Glutamate Receptors in Mammalian and Avian Auditory System

Zheng-Quan Tang et al. HSOA Trends Anat Physiol. 2018.

Abstract

Glutamate, as the major excitatory neurotransmitter used in the vertebrate brain, activates ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs), which mediate fast and slow neuronal actions, respectively. mGluRs play important modulatory roles in many brain areas, forming potential targets for drugs developed to treat brain disorders. Here, we review studies on mGluRs in the mammalian and avian auditory system. Although anatomical expression of mGluRs in the cochlear nucleus has been well characterized, data for other auditory nuclei await more systematic investigations especially at the electron microscopy level. The physiology of mGluRs has been extensively studied using in vitro brain slice preparations, with a focus on the auditory circuitry in the brainstem. These in vitro physiological studies have demonstrated that mGluRs participate in synaptic transmission, regulate ionic homeostasis, induce synaptic plasticity, and maintain the balance between Excitation and Inhibition (E/I) in a variety of auditory structures. However, the modulatory roles of mGluRs in auditory processing remain largely unclear at the system and behavioral levels, and the functions of mGluRs in auditory disorders remain entirely unknown.

Keywords: Auditory processing; Excitotoxicity; Neuromodulation; Neurotransmission; Synaptic plasticity; mGluR.

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Conflict of interest statement

Conflict of Interest The author declares no competing financial interests.

Figures

Figure 1:
Figure 1:
Schematic drawing summarizing the anatomy and physiology of mGluRs in the mammalian auditory system. At the cochlea, postsynaptic group I mGluRs participate in the excitatory trans mission at the synapses between Inner Hair Cells (IHC) and Spiral Ganglion (SG) neurons, and presynaptic group I mGluRs enhance the release of ACH by the olivocochlear efferent fibers. Group II mGluRs suppress GABA release of the efferent system via a presynaptic mechanism. Postsynaptic group II and III mGluRs contribute to the induction of long-term plasticity of the excitatory input in the Dorsal Cochlear Nucleus (DCN). In the Ventral Cochlear Nucleus (VCN), postsynaptic group I mGluRs increase the excitability of bushy cells. In the Medial Nucleus of Trapezoid Body (MNTB), postsynaptic group I mGluRs mediate a retro-suppression of glutamatergic transmission, whereas presynaptic group III mGluRs inhibit glutamate release via modulating voltage-gated Ca2+ channels. The inhibitory input from the MNTB to the Lateral Superior Olive (LSO) is modulated by presynaptic group II mGluRs, whereas the excitatory input from the VCN to the LSO is modulated by presynaptic group II and III mGluRs. Postsynaptic group I an d II mGluRs regulate intracellular Ca2+ concentration in developing LSO neurons. In the Inferior Colliculus (IC), presynaptic group II mGluRs suppress both synaptic excitation and inhibition. Postsynaptic group I mGluRs enhance while group II mGluRs suppress the cellular excitability. In the thalamus, weak evidence suggests that postsynaptic group I and II mGluRs depolarize neurons of the Medial Geniculate Body (MGB). There exist multiple cell types in most of the structures depicted here especially in the DCN, VCN, and the IC. The schematic drawing does not reflect this complexity, and limited information on the physiology of mGluRs in different cell types is available. In layers 2/3 pyramidal cells in the Auditory Cortex (AC), presynaptic mGluRs (possibly group I and II mGluRs) inhibit both excitatory and inhibitory inputs that originate from layer 6. Postsynaptic group I mGluRs are activated by the thalamocortical input and mediate membrane depolarization in class 2 cells (modulator neurons). In layer 4, group I mGluRs activated by the intracortical pathway from layer 6 depolarize pyramidal neurons, whereas postsynaptic group II mGluRs produce inhibition via activation o f GIRK channels. Also in layer 4, presynaptic group II mGluRs produce strong inhibition of excitatory transmission of the thalamocortical pathway. In layers 3/4, group I mGluRs are required for the induction of LTD and LTP of the thalamocortical excitatory transmission. In layers 2/3 and 4, presynaptic group II mGluRs suppress GABA release. In this and the sub-sequent figure, pre- and post-: presynaptic and postsynaptic, respectively. I, II, and III: group I, II, and III mGluRs.
Figure 2:
Figure 2:
Schematic drawing summarizing the anatomy and physiology of mGluRs in the avian auditory brainstem. After entering the brainstem, the auditory nerve (8th n.) bifurcates and innervates the two subnuclei of the cochlear nucleus, NA and NM. The NL receives bilateral excitatory inputs from NM. All three nuclei (NM, NL, NA) receive feedback inhibition from the ipsilateral SON, which is driven by excitatory inputs from NL and NA. All three groups of mGluRs are involved in presynaptic modulation of the inhibitory transmission in NM neurons. Multiple mGluRs (with controversial identity) suppress both excitatory and inhibitory transmission in NL, possibly in a tuning frequency-dependent manner. Presynaptic mGluRs also modulate the excitatory transmission at NA, without affecting the excitatory inputs to NM. Postsynaptic mGluRs regulate cellular excitability of NA neurons, and modulate voltage-gated Ca2+ channels in NM neurons. In NL, postsynaptic group II mGluRs enhance high-threshold Kv channels. Studies on mGluR-mediated modulation in the SON are completely lacking. NA: Cochlear Nucleus Angularis; NM: Cochlear Nucleus Magnocellularis; NL: Nucleus Laminar- is; SON: Superior Olivary Nucleus.
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