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Sarah A Minton, James W Fransen, Susumu Tomita, Jonathan B Demb, Bart Gerard Borghuis; Parallel OFF bipolar cell pathways develop and function in the absence of dendritic kainate receptors. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1336.
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© ARVO (1962-2015); The Authors (2016-present)
Photoreceptors signal their light responses through parallel 'ON' and 'OFF' bipolar cell pathways. In mature mouse and primate retina, pharmacology experiments suggested that all OFF bipolar cells receive excitatory input from the cone photoreceptors through kainate-type glutamate receptors. Here, we tested how genetic deletion of kainate receptors impacts the structural and functional development of OFF signaling pathways in mouse retina.
Morphologically identified OFF-type ganglion cells were recorded by whole-cell patch clamp in retinas of kainate receptor knockout mice (GluK-/-). Bipolar cell morphology was studied with immunohistochemistry and confocal microscopy. The ultrastructure of cone-->bipolar cell synapses was studied using transmission electron microscopy.
OFF bipolar cells in the retina of GluK-/- mice showed normal morphology, and extended dendrites to their photoreceptor terminal targets in the outer plexiform layer (OPL). Ultrastructural analysis of the OPL showed no apparent changes compared with wild-type (WT). Excitatory currents recorded from OFF-type ganglion cells showed that OFF pathway function was largely intact, with normal response amplitudes, receptive field size, and contrast sensitivity. Moreover, OFF bipolar pathways maintained their functional identity, with sustained and transient responses in anatomically defined OFF-delta and OFF-alpha cells, respectively. OFF ganglion cell responses in GluK-/- retina showed a slight (~30 ms) delay relative to WT. Pharmacological block of kainate receptors with ACET in WT retina reproduced this delay, ruling out a developmental adaptation in GluK-/- mice. Blocking ON bipolar cell input with L-AP4 in GluK-/- retina eliminated light-evoked responses in OFF ganglion cells, demonstrating that OFF responses were driven by ON bipolar pathways, presumably through synaptic input from ON amacrine cells onto OFF bipolar cell terminals.
Major structural and functional characteristics of the OFF pathway, including transient and sustained signaling, are independent of the dendritic receptors expressed by OFF bipolar cells. In the absence of direct dendritic input to OFF bipolar cells, strong, redundant signaling pathways in WT and GluK-/- mice allow ON amacrine pathways to maintain near-normal signaling in parallel OFF pathways.
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