Extracellular and whole-cell light-evoked responses of mouse retinal ganglion cells were recorded in the presence of the mGluR8 selective agonist, (S) . Off-light responses were reversibly reduced in the presence of DCPG in wild-type but not in mGluR8-deficient retinas. On-responses were only marginally modulated by DCPG. During Off-responses, DCPG suppressed both excitatory and inhibitory synaptic conductances suggesting that mGluR8 receptor activity reduces glutamate release from bipolar cell terminals and possibly also the release of an inhibitory neurotransmitter from amacrine cell processes.
Keywords
Retina; metabotropic glutamate receptorGlutamate is the main excitatory neurotransmitter in the retina mediating transmission from photoreceptors to bipolar cells, and from bipolar cells to amacrine and ganglion cells. It exerts its effects via ionotropic and metabotropic receptors, thus serving multiple roles in visual signal processing (for reviews see Brandstätter et al., 1998;Thoreson and Witkovsky, 1999). Ionotropic glutamate receptors (NMDA, AMPA, and kainate subtypes) are ligand-gated ion channels that activate non-selective cation channels (Hollmann and Heinemann, 1994). Metabotropic glutamate receptors (mGluRs) can be either pre-or postsynaptic, and modulate G protein-mediated intracellular second messenger cascades that elicit diverse effects on neuronal function (Pin and Duvoisin, 1995).The mGluRs are classified into three groups based on sequence homology, second messenger coupling and pharmacological selectivity (Conn and Pin, 1997). Group-I receptors (mGluR1 and 5) are coupled to the stimulation of phospholipase C, whereas group-II (mGluR2 and 3) and 6, 7, and 8) Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Author ManuscriptNeuroscience. Author manuscript; available in PMC 2011 March 31. Hartveit et al., 1995).The best functionally characterized of the retinal mGluRs is the group-III receptor mGluR6, which occurs postsynaptically at the dendritic tips of On-bipolar cells (Nomura et al., 1994). The mGluR6 receptors transduce the light-evoked hyperpolarization of photoreceptors into a depolarizing response at bipolar cells by gating an excitatory cation channel (Slaughter and Miller, 1981;Shiells and Falk, 1990;Nawy and Jahr, 1991). The compound, L-2-amino-4-phosphonobutyrate (L-AP4, also L-APB), is a selective agonist of group-III mGluRs and its activation of mGluR6 has been widely used to selectively block the On-pathway (Massey et al., 1983;Schiller et al., 1986;Bodnarenko and Chalupa, 1993;Kittila and Massey, 1995). Howeve...