Abstract
Blockade of retinal waves prevents the segregation of retinogeniculate afferents into eye-specific layers in the visual thalamus. However, the key features of retinal waves that drive this refinement are controversial. Some manipulations of retinal waves lead to normal eye-specific segregation but others do not. By comparing retinal spiking patterns in several mutant mice with differing levels of eye-specific segregation, we show that the presence of high-frequency bursts synchronized across neighboring retinal ganglion cells correlates with robust eye-specific segregation and that the presence of high levels of asynchronous spikes does not inhibit this segregation. These findings provide a possible resolution to previously described discrepancies regarding the role of retinal waves in retinogeniculate segregation.
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Acknowledgements
We thank E.J. Chichilnisky for the multielectrode array and technical support, D. Paul for the Cx36−/− mice, J. Goldstein and W. Pak for technical support, and D.E. Feldman, N. Spitzer and L. Boulanger for a critical reading of this manuscript. Supported in part by a US National Science Foundation Graduate Research Fellowship, the Klingenstein Foundation, Whitehall Foundation, March of Dimes, McKnight Scholars Fund and the National Institutes of Health (grant number NS13528-01A1).
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Supplementary information
Supplementary Fig. 1
Correlation index does not change as a function of bin size. Correlation index was computed as previously stated for binwidths from 10 ms to 500 ms. (GIF 21 kb)
Supplementary Fig. 2
β-galactosidase expression in the developing dLGN. Both Cx36–/– (top row) and Cx36+/– (bottom row) dLGNs reveal a transient expression of β-gal throughout development. Scale = 100 µm. Insets: β-gal expression is localized to somata within the dLGN. Scale = 5 µm. The existence of Cx36 in the dLGN cannot account for our results since eye–specific segregation was normal in Cx36–/– mice. (JPG 43 kb)
Supplementary Fig. 3
Cell-attached recording of a single burst from a P10 Cx36–/– RGC indicates spike adaptation occurs in RGCs. Recordings were made from acutely isolated Cx36–/– retinas perfused with oxygenated ACSF and warmed to 32-35° C. The internal electrode solution contained (in mM): 98.3 potassium gluconate, 1.7 KCl, 0.6 EGTA, 5 MgCl2, 2 Na2-ATP, 0.3 GTP, and 40 HEPES, pH 7.25, with KOH. Voltage-clamp cell-attached recordings were made using an Axopatch 200B amplifier and pClamp6 software (Axon Instruments, Foster City, CA). (GIF 9 kb)
Supplementary Video 1
Time-Lapse Representation of Firing Rates Recorded in Wild-Type and Cx36–/– Retinal Neurons Using a Multielectrode Array For each movie, dots represent the positions of electrodes in the multielectrode array on which discreet units were recorded. The size of each dot in every frame represents the average firing rate recorded over 500 ms on that electrode, larger dots correspond to higher firing rates. The movie plays at 10 frames/s (i.e., five times as fast as real time) and represents five minutes of recording. Only electrodes in which unambiguous units could be isolated from each other are illustrated. If multiple units were recorded on the same electrode, units were randomly eliminated so only one unit was portrayed on each electrode. (MOV 625 kb)
Supplementary Video 2
Time-Lapse Representation of Firing Rates Recorded in Wild-Type and Cx36–/– Retinal Neurons Using a Multielectrode Array For each movie, dots represent the positions of electrodes in the multielectrode array on which discreet units were recorded. The size of each dot in every frame represents the average firing rate recorded over 500 ms on that electrode, larger dots correspond to higher firing rates. The movie plays at 10 frames/s (i.e., five times as fast as real time) and represents five minutes of recording. Only electrodes in which unambiguous units could be isolated from each other are illustrated. If multiple units were recorded on the same electrode, units were randomly eliminated so only one unit was portrayed on each electrode. (MOV 734 kb)
Supplementary Video 3
Time-Lapse Representation of Firing Rates Recorded in Wild-Type and Cx36–/– Retinal Neurons Using a Multielectrode Array For each movie, dots represent the positions of electrodes in the multielectrode array on which discreet units were recorded. The size of each dot in every frame represents the average firing rate recorded over 500 ms on that electrode, larger dots correspond to higher firing rates. The movie plays at 10 frames/s (i.e., five times as fast as real time) and represents five minutes of recording. Only electrodes in which unambiguous units could be isolated from each other are illustrated. If multiple units were recorded on the same electrode, units were randomly eliminated so only one unit was portrayed on each electrode. (MOV 684 kb)
Supplementary Video 4
Time-Lapse Representation of Firing Rates Recorded in Wild-Type and Cx36–/– Retinal Neurons Using a Multielectrode Array For each movie, dots represent the positions of electrodes in the multielectrode array on which discreet units were recorded. The size of each dot in every frame represents the average firing rate recorded over 500 ms on that electrode, larger dots correspond to higher firing rates. The movie plays at 10 frames/s (i.e., five times as fast as real time) and represents five minutes of recording. Only electrodes in which unambiguous units could be isolated from each other are illustrated. If multiple units were recorded on the same electrode, units were randomly eliminated so only one unit was portrayed on each electrode. (MOV 1266 kb)
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Torborg, C., Hansen, K. & Feller, M. High frequency, synchronized bursting drives eye-specific segregation of retinogeniculate projections. Nat Neurosci 8, 72–78 (2005). https://doi.org/10.1038/nn1376
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DOI: https://doi.org/10.1038/nn1376
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