Abstract
Abstract: :
Purpose: The ON pathway in the retina is thought to be activated exclusively by type 6 metabotropic glutamate receptors (mGluR6) expressed in the dendrites of ON-type bipolar cells: Unlike in wild-type (WT) animals, mGluR6 null (-/-) mice have no ERG b-wave and no fast ON response from the retinal ganglion cells (RGCs), consistent with a loss of light-evoked signaling in the ON bipolar cells. However, a delayed ON response to steps of light has been recorded in the superior colliculus of these mice. We sought to determine the existence and nature of this delayed ON response in the retina. Methods: We tested responses of RGCs in mGluR6 -/- retinas using a multi-electrode array, which allows extracellular recording of action potential responses from several dozen RGCs simultaneously. Results: In mGluR6 -/- mouse retinas, essentially no RGC responses were recorded in the first 300 msec after the onset of a light stimulus, but 70 +/- 12 % (n = 5 retinas; mean +/- SD) of the RGCs had a delayed ON response with an onset latency greater than 500 msec. This delayed ON response in mGluR6 -/- mice was not prevented by antagonists to all three classes of metabotropic receptor, to cholinergic receptors (muscarinic or nicotinic), or to GABA receptors. These responses are not driven by melanopsin in RGCs: The delayed ON response did not resemble that typically recorded from melanopsin-positive RGCs, being quicker in onset and shorter in duration; melanopsin immunoreactivity was comparable in WT and mGluR6 -/- mouse retinas, inconsistent with an upregulation of melanospin-containing RGCs in the null mice. Conclusions: Retinal circuitry in mGluR6 -/- mice allows for the generation of a delayed ON response in a large subset of RGCs. This ON response is not produced by activation of metabotropic glutamate receptors, cholinergic receptors, GABA receptors, or intrinsically light-responsive, melanopsin-positive RGCs.
Keywords: bipolar cells • retinal connections, networks, circuitry • excitatory amino acid receptors