Group II Metabotropic Glutamate Receptors Modulate Sound Evoked and Spontaneous Activity in the Mouse Inferior Colliculus

Abstract

Little is known about the functions of group II metabotropic glutamate receptors (mGluRs2/3) in the inferior colliculus (IC)-a midbrain structure that is a major integration region of the central auditory system. We investigated how these receptors modulate sound-evoked and spontaneous firing in the mouse IC in vivo. We first performed immunostaining and tested hearing thresholds to validate VGAT-ChR2 transgenic mice on a mixed CBA/CaJ x C57BL/6J genetic background. Transgenic animals allowed for optogenetic cell type identification. Extracellular single neuron recordings were obtained before and after pharmacological mGluR2/3 activation. We observed increased sound-evoked firing-as assessed by the rate-level functions-in a subset of both GABAergic and non-GABAergic IC neurons following mGluR2/3 pharmacological activation. These neurons also displayed elevated spontaneous excitability and were distributed throughout the IC area tested, suggesting a widespread mGluR2/3 distribution in the mouse IC. SignificanceGlutamate is the primary excitatory neurotransmitter in the brain. It binds to both ionotropic and metabotropic glutamate receptors. Fast ionotropic receptors generate rapid synaptic transmission, whereas slower metabotropic glutamate receptors (mGluRs) modulate this synaptic transmission. Here, we discovered that activation of group II mGluRs enhances sound-evoked and spontaneous neuronal firing in the inferior colliculus-the hub of the central auditory system. We used transgenic mice which allowed for identification of excitatory and inhibitory neurons and found that both these cell types are modulated by group II mGluRs. Our results provide better understanding of mGluR modulatory roles, which is crucial in opening avenues for using mGluR-targeting drugs to treat hearing Glutamate is the primary excitatory neurotransmitter in the brain. It binds to both ionotropic and metabotropic glutamate receptors (mGluRs). Ionotropic receptors, which are ligand-gated cation channels, are important for rapid signal transmission, whereas mGluRs act via G-protein coupled second messenger cascades and are relatively slower. In general, mGluRs have been thoroughly investigated due to their potential as therapeutic targets in several psychiatric and neurological disorders

Long-Duration Sound-Induced Facilitation Changes Population Activity in the Inferior Colliculus

“…The mechanism for LDS-induced facilitation could involve the activation of metabotropic glutamate receptors (mGluR). Activation of group 1 and 2 mGluRs increases spontaneous activity in the IC, and group 2 mGluR activation can enhance sound responses ( Voytenko and Galazyuk, 2011 ; Kristaponyte et al, 2021 ). mGluR are located perisynaptically on the presynaptic or postsynaptic terminal depending on their subtype ( Baude et al, 1993 ; Nusser et al, 1994 ; Shigemoto et al, 1997 ; Niswender and Conn, 2010 ).…”