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Abstract
Retinal ganglion cells that express the photopigment melanopsin are intrinsically photosensitive (ipRGCs) and exhibit robust synaptically driven ON-responses to light, yet they will continue to depolarize in response to light when all synaptic input from rod and cone photoreceptors is removed. The light-evoked increase in firing of classical ganglion cells is determined by synaptic input from ON-bipolar cells in the proximal sublamina of the inner plexiform layer. OFF-bipolar cells synapse with ganglion cell dendrites in the distal sublamina of the inner plexiform layer. Of the several types of ipRGC that have been described, M1 ipRGCs send dendrites exclusively into the OFF region of the inner plexiform layer where they stratify near the border of the inner nuclear layer. We tested whether M1 ipRGCs with dendrites restricted to the OFF sublamina of the inner plexiform layer receive synaptic ON-bipolar input by examining light-induced gene expression in vivo using melanopsin knockout mice. Mice in which both copies of the melanopsin gene (opn4) have been replaced with the tau-lacZ gene (homozygous tau-lacZ+/+ knockin mice) are melanopsin knockouts (opn4−/−) but M1 ipRGCs are specifically identified by their expression of β-galactosidase. Approximately 60% of M1 ipRGCs in Opn4−/− mice exposed to 3 hrs of light expressed c-Fos; no β-galactosidase-positive RGCs expressed c-Fos in the dark. Intraocular application of L-AP4, a compound which blocks transmission of visual signals between photoreceptors and ON-bipolar cells significantly reduced light-evoked c-Fos expression in M1 ipRGCs compared to saline injected eyes (66% saline vs 27% L-AP4). The results are the first description of a light-evoked response in an ipRGC lacking melanopsin and provide in vivo confirmation of previous in vitro observations illustrating an unusual circuit in the retina in which ganglion cells sending dendrites to the OFF sublamina of the inner plexiform layer receive excitatory synaptic input from ON-bipolar cells.
Highlights
Retinal ganglion cells that express the photopigment melanopsin are intrinsically photosensitive and depolarize in response to light in the absence of all synaptic input from rod and cone photoreceptors [1,2,3,4]
The number of Fos-positive b-galactosidase cells is presented as a percentage of the number of b-galactosidase cells observed for each eye of each animal (#1–#3) after intravitreal injection of 1 ml saline or 1 ml L-AP4 (1 mM) followed by 3 h of light stimulation or 3 h of darkness. doi:10.1371/journal.pone.0004984.t002
IpRGCs) and these neurons send dendrites to the OFF substrata of the inner plexiform layer (IPL) where they stratify near the border of the inner nuclear layer (INL) [14]
Summary
Retinal ganglion cells that express the photopigment melanopsin are intrinsically photosensitive (ipRGCs) and depolarize in response to light in the absence of all synaptic input from rod and cone photoreceptors [1,2,3,4]. Dendrites of ipRGCs in the inner plexiform layer (IPL) are postsynaptic to bipolar and amacrine cells [5,6,7] and ipRGCs receive robust synaptically driven excitatory input [8,9,10,11,12]. ON and OFF functional channels are created as the result of the differential expression of glutamate receptors on the dendrites of bipolar cells. ON bipolar cells use a metabotropic receptor, mGluR6, which functionally inverts the light-activated hyperpolarizations of photoreceptors into a depolarization [16,17,18,19]. The separate ON and OFF channels established at the photoreceptor-to-bipolar synapse are retained by conventional ganglion cells by the restriction of their dendrites to either the upper (OFF) or lower (ON) stratum of the IPL to receive synapses from OFF and ON bipolar cells, respectively [21]
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