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David I Swygart, Greg Schwartz, Rachel O Wong, Wan-Qing Yu; Functional divergence at the mouse type 6 bipolar cell terminal. Invest. Ophthalmol. Vis. Sci. 2019;60(9):552.
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© ARVO (1962-2015); The Authors (2016-present)
While neurons were long thought to represent the fundamental computational units of the nervous system, a large body of work over the last 50 years has revealed subcellular functional compartmentalization. We hypothesize that such subcellular compartmentalization in retinal bipolar cells allow individual bipolar cells to transmit different functional signals through different synapses. To test this hypothesis, we examined the output of the type 6 bipolar cell onto two potential downstream retinal ganglion cell types (PixON and On Alpha RGC types).
Light sensitive retinas were extracted from adult mice and whole mounted. Light responses of retinal ganglion cells (RGCs) were recorded under cell attached and whole cell configurations. After physiological recording, the retinas were imaged with two-photon microscopy, underwent immunohistochemical labeling and confocal microscopy, or were sectioned and underwent serial electron microscopy.
Immunohistochemical staining shows that the majority of excitatory input synapses to the On Alpha and PixON RGCs are made by the type 6 bipolar cell. Serial electron microscopy shows that the same type 6 bipolar cell makes synapses onto both the On Alpha and PixON RGC. Additionally, these two RGC types have high cross-correlation of excitatory input, indicating that they both receive excitatory input from the same neuron. Although receiving excitatory input from the same bipolar cell type, excitatory input to the On Alpha RGC has weak surround suppression while excitatory input to the PixON RGC has strong surround suppression. This difference in surround suppression was reduced by application of GABA receptor antagonists or voltage-gated sodium channel blockers.
We show that an individual type 6 bipolar cell is able to provide input with strong surround suppression to the one type of RGC (PixON RGC) while simultaneously providing input with weak surround suppression to a different type of RGC (On Alpha RGC). This subcellular signal divergence occurs at the terminal of the type 6 bipolar cell via GABAergic presynaptic inhibition from wide-field spiking amacrine cells. These findings indicate that each terminal of a single bipolar cell could potentially carry a unique visual signal. This expands the number of visual channels in the inner retina allowing for increased parallelism at the earliest stages of visual processing.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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