Different Mechanisms Generate Maintained Activity in ON and OFF Retinal Ganglion Cells

Margolis, David J.; Detwiler, Peter B.

doi:10.1523/jneurosci.0130-07.2007

Cited by 196 publications

(373 citation statements)

References 80 publications

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“…Therefore, more than 14% of narrow correlation is expected if we restrict cell pairs only to OFF-OFF pairs. The finding that only OFF cells, but not ON cells, exhibit rebound excitation (Margolis & Detwilder, 2007) is in good agreement with our results that the major cell types showing narrow correlation were OFF cell pairs.…”

Section: Narrow Correlationsupporting

confidence: 92%

Functional Connectivity Map of Retinal Ganglion Cells for Retinal Prosthesis

Ryu

Kim

et al. 2008

Korean J Physiol Pharmacol

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Retinal prostheses are being developed to restore vision for the blind with retinal diseases such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Among the many issues for prosthesis development, stimulation encoding strategy is one of the most essential electrophysiological issues. The more we understand the retinal circuitry how it encodes and processes visual information, the greater it could help decide stimulation encoding strategy for retinal prosthesis. Therefore, we examined how retinal ganglion cells (RGCs) in in-vitro retinal preparation act together to encode a visual scene with multielectrode array (MEA). Simultaneous recording of many RGCs with MEA showed that nearby neurons often fired synchronously, with spike delays mostly within 1 ms range. This synchronized firing -narrow correlation -was blocked by gap junction blocker, heptanol, but not by glutamatergic synapse blocker, kynurenic acid. By tracking down all the RGC pairs which showed narrow correlation, we could harvest 40 functional connectivity maps of RGCs which showed the cell cluster firing together. W e suggest that finding functional connectivity map would be useful in stimulation encoding strategy for the retinal prosthesis since stimulating the cluster of RGCs would be more efficient than separately stimulating each individual RGC.

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Section: Narrow Correlationsupporting

confidence: 92%

Functional Connectivity Map of Retinal Ganglion Cells for Retinal Prosthesis

Ryu

Kim

et al. 2008

Korean J Physiol Pharmacol

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“…This argues that asymmetries between ON and OFF pathways are likely to be cell type specific. Future experiments are needed to determine whether these variations result from differences in the balance of excitatory and inhibitory synaptic inputs, the mechanism of spike generation in RGCs, or a combination of both (Margolis and Detwiler, 2007). In addition, how precisely RGC types identified in our study match up with those characterized in whole cell (Pang et al, 2003;Murphy and Rieke, 2006) and multielectrode recordings using square-wave modulated full-field stimulation (Carcieri et al, 2003) will require additional experiments.…”

Section: Light Response Properties Of Rgcs In Control and Dko Micementioning

confidence: 93%

Genetic Control of Circuit Function:Vsx1andIrx5Transcription Factors Regulate Contrast Adaptation in the Mouse Retina

Kerschensteiner¹,

Liu²,

Cheng³

et al. 2008

J. Neurosci.

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Transcriptional programs guide the specification of neural cell types in the developing nervous system. However, it is unclear whether such programs also control specific aspects of neural circuit function at maturity. In the mammalian retina, Vsx1 and Irx5 transcription factors are present in a subset of bipolar interneurons that convey signals from photoreceptors to ganglion cells. The biased expression of Vsx1 and Irx5 in hyperpolarizing OFF compared with depolarizing ON bipolar cells suggests that these transcription factors may selectively regulate signal processing in OFF circuits. To test this hypothesis, we generated mice lacking both Vsx1 and Irx5. Bipolar cells in these mice were morphologically normal, but the expression of cell-specific markers in some OFF but not ON bipolar cells was reduced or absent. To assess visual function in Vsx1 Irx5Ϫ/Ϫ retinas, we recorded light responses from ensembles of retinal ganglion cells (RGCs). We first identified functional RGC types in control mice and describe their response properties and adaptation to temporal contrast using a simple linear-nonlinear model. We found that space-time receptive fields of RGCs are unchanged in Vsx1 Irx5Ϫ/Ϫ mice compared with control retinas. In contrast, response threshold, gain, and range were lowered in a cell-type-specific manner in OFF but not ON RGCs in Vsx1 Irx5Ϫ/Ϫ retinas. Finally, we discovered that the ability to adapt to temporal contrast is greatly reduced in OFF RGCs in the double mutant, suggesting that Vsx1 and Irx5 control specific aspects of visual function in circuits of the mammalian retina.

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“…We tested these predictions by simultaneously measuring synaptic input to an AII amacrine cell (held at the reversal potential for inhibitory synaptic input) and an Off RGC (held at the reversal potential for excitatory synaptic input) evoked by steps in light intensity from darkness; we focused on Off transient RGCs, a class of RGC distinguished by its large soma and transient bursts of action potentials at light offset 8,16,24 . The amplitude of excitatory synaptic input to AII amacrine cells and the IPSC in Off transient RGCs differed by more than an order of magnitude (Fig.…”

Section: Circuitry Governing Synaptic Input To On and Off Rgcsmentioning

confidence: 99%

Signals and noise in an inhibitory interneuron diverge to control activity in nearby retinal ganglion cells

Murphy¹

2008

Nat Neurosci

106

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Information about sensory stimuli is represented by spatiotemporal patterns of neural activity. The complexity of the central nervous system, however, frequently obscures the origin and properties of signals and noise that underlie these activity patterns. We minimized this constraint by examining mechanisms governing correlated activity in mouse retinal ganglion cells (RGCs) under conditions where light-evoked responses traverse a specific circuit -the rod bipolar pathway. Signals and noise in this circuit produced correlated synaptic input to neighboring On and Off RGCs. Temporal modulation of light intensity did not alter the degree to which noise in the input to nearby RGCs was correlated, and action potential generation in individual RGCs was largely insensitive to differences in network noise generated by dynamic and static light stimuli. Together, these features enable noise in shared circuitry to diminish simultaneous action potential generation in neighboring On and Off RGCs under a variety of conditions. Differences in the responses of neurons in parallel pathways to sensory stimuli depend on many features of network input (e.g.,1 -4 ), including: (1) differences in the source and properties of excitatory and inhibitory synaptic input; (2) the prevalence of noise in shared circuitry that causes correlated variability in synaptic input; and (3) the source and properties of noise that limits the fidelity of action potential generation in individual neurons. Ambiguities in the signals that anatomically-defined circuits convey and/or the sources of input that parallel pathways receive frequently obscure the contribution of these factors to the functional properties of specific neurons.The mammalian retina provides an excellent opportunity to identify the contribution of distinct and shared circuitry to the functional properties of neurons in parallel pathways (reviewed in 5-7 ). Activity in On and Off RGCs is influenced by distinct features of light stimuli, and dim fluctuating light stimuli modulate action potential generation in RGCs via specific and tractable circuitry 8,9 -the rod bipolar pathway (rod -> rod bipolar -> AII amacrine -> cone bipolar terminal -> RGC; reviewed in 10-12 ). The AII amacrine cell plays a fundamental role in this circuitry by segregating signals into On and Off pathways; light-evoked depolarization of AII amacrine increases excitatory synaptic input to On RGCs through gap junctions with the synaptic terminals of On cone bipolar cells and decreases excitatory synaptic input to Off RGCs via glycinergic inhibition of the synaptic terminals of Off cone bipolar cells (Fig. 1a ).We find that AII amacrine cells, in addition to modulating excitatory synaptic input to On and Off RGCs, provide direct inhibitory synaptic input to Off RGCs. This circuitry enables lightevoked signals in AIIs to generate anti-correlated action potentials in On and Off RGCs in two fundamentally distinct ways: (1) via negatively correlated excitatory synaptic input to On and

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Different Mechanisms Generate Maintained Activity in ON and OFF Retinal Ganglion Cells

Cited by 196 publications

References 80 publications

Functional Connectivity Map of Retinal Ganglion Cells for Retinal Prosthesis

Functional Connectivity Map of Retinal Ganglion Cells for Retinal Prosthesis

Genetic Control of Circuit Function:Vsx1andIrx5Transcription Factors Regulate Contrast Adaptation in the Mouse Retina

Signals and noise in an inhibitory interneuron diverge to control activity in nearby retinal ganglion cells

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