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Benjamin Murphy-Baum, Geoff deRosenroll, Varsha Jain, Alex Hoggarth, Gautam Awatramani; Spatiotemporal coordination of excitation and inhibition mediated by starburst amacrine cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1868.
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© ARVO (1962-2015); The Authors (2016-present)
Neural circuits often rely on the integration of well-coordinated excitation and inhibition (E/I) for their computations. Two problems in maintaining balanced E/I are coordination in time—since mistimed conductances are unlikely to interact—and coordination in space—since precisely timed conductances won’t interact if they aren’t spatially coincident. Under weak stimulus conditions, during which network variability is high, coordinating E/I becomes a challenge and limits the computational capacity of neural circuits. Recently, we demonstrated that low contrast responses in direction selective ganglion cells (DSGCs) are largely shaped by ACh and GABA released from starburst amacrine cells. Here, we examine how starburst ACh/GABA is coordinated in space and time.
DSGCs were targeted for patch clamp recordings in mice (≥ P30). Temporal coordination of E/I was measured by oscillating the DSGC membrane potential between the cation and chloride reversal potentials at 100 Hz, so as to near-simultaneously measure E/I. In similar experiments, E/I to DSGCs were optogenetically evoked in mice where the presynaptic starburst amacrine cells express ChR2. Spatial coordination of E/I was estimated using 2-photon Ca2+ imaging of DSGC dendrites. Responses were evoked using low contrast moving visual stimuli.
Low contrast visual stimuli evoked spikes with highly variable onset times compared to high contrast stimuli (σ = 103 ± 16 ms at low contrast; σ = 26 ± 7 ms at high contrast; P = 0.005, N = 6). Despite higher spike time variability, directional tuning was maintained. Moreover, the onset of excitation and inhibition tightly co-fluctuated, and their noise residuals were highly correlated (correlation coefficient = -0.47 ± 0.09, N = 7) on a fine timescale (width of Gaussian fit to cross-correlograms = 29 ± 4 ms). ChR2-evoked EPSCs and IPSCs also had correlated noise residuals with similar temporal structure. In addition, we found Ca2+ signals in individual DSGC dendrites were directionally tuned. Ca2+ signals in neighboring dendrites, although sharply tuned, showed distinct fluctuations in directional tuning.
The starburst network is capable of generating mixed excitation and inhibition with a high degree of spatial and temporal correlations across the dendritic arbors of DSGCs, allowing the DS circuit to circumvent the limits on its computation imposed by network variability.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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