An Old Neuron Learns New Tricks: Redefining Motion Processing in the Primate Retina

Murphy-Baum, Benjamin L.; Awatramani, Gautam B.

doi:10.1016/j.neuron.2018.03.007

“…However, less is known about the specific roles of gap junctions in mature RPE. In the retina, gap junctions are known to have myriad roles, such as receptive field size signal correlation ( Devries, 1999 ) and motion detection ( Murphy-Baum and Awatramani, 2018 ), and both light adaptation and circadian rhythm have been shown to alter the electrical coupling of the underlying neural circuits ( Vasconcellos et al, 2005 ; Rassi Gabriel et al, 2011 ). As our results demonstrate that both gap junctions and Cx43 hemichannels can control the electrical excitability of RPE by altering the input resistance, it is plausible the connectivity could enable synchronization of the essential functions of RPE, particularly as the junctions facilitate signaling across wide regions.…”

Section: Discussionmentioning

confidence: 99%

Gap junctions and connexin hemichannels both contribute to the electrical properties of retinal pigment epithelium

Fadjukov

¹

,

Wienbar

²

,

Hakanen

³

et al. 2022

Journal of General Physiology

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Gap junctions are intercellular channels that permit the transfer of ions and small molecules between adjacent cells. These cellular junctions are particularly dense in the retinal pigment epithelium (RPE), and their contribution to many retinal diseases has been recognized. While gap junctions have been implicated in several aspects of RPE physiology, their role in shaping the electrical properties of these cells has not been characterized in mammals. The role of gap junctions in the electrical properties of the RPE is particularly important considering the growing appreciation of RPE as excitable cells containing various voltage-gated channels. We used a whole-cell patch clamp to measure the electrical characteristics and connectivity between RPE cells, both in cultures derived from human embryonic stem cells and in the intact RPE monolayers from mouse eyes. We found that the pharmacological blockade of gap junctions eliminated electrical coupling between RPE cells, and that the blockade of gap junctions or Cx43 hemichannels significantly increased their input resistance. These results demonstrate that gap junctions function in the RPE not only as a means of molecular transport but also as a regulator of electrical excitability.

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“…dC n dx (7) etc Method 3: The diffusion of dye through a homologously coupled cell network (such as horizontal cells) following cut-loading can be described as the diffusion of a substance along one axis using Fick's second law of diffusion 28 8 Where C is concentration of the diffusing substance, t is time in seconds, D is the diffusion coe cient (cm 2 .s −1 ) and x is distance (cm).…”

Section: E (λ) mentioning

confidence: 99%

“…These coupled networks facilitate the rapid, lateral spread of signals across the retina that complements slower synaptic transmission. Functionally, cell-coupling between retinal neurons modulates receptive eld size, facilitates the transition between photopic and scotopic retinal states and contributes to signal averaging, synchrony and motion detection [5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Analytical Methods for Assessing Retinal Cell Coupling Using Cut-Loading

Myles

¹

,

McFadden

²

2021

Preprint

0

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Electrical coupling between retinal neurons contributes to the functional complexity of visual circuits. “Cut-loading” methods allow simultaneous assessment of cell-coupling between multiple retinal cell-types, but existing analysis impedes direct comparison with gold standard direct dye injection techniques. Therefore cut-loading was used to assess coupling strength in a-type horizontal cells in dark-adapted Guinea pig retinae (n=29) using the standard protocol (Method 1) compared with two non-linear methods. Method 1 describes the distance of dye-diffusion (space constant), while Method 2 extracted the coupling coefficient (kj) and Method 3 measured the diffusion coefficient (De). Dye transfer was measured after one of five diffusion times (1-20 mins), or with a coupling inhibitor, meclofenamic acid (MFA) (50–500µM after 20 mins diffusion). Method 1 includes background fluorescence, producing less accurate coupling estimates than measuring the fluorescence of individual cell-soma (p<0.001). The space constant (Method 1) increased with diffusion time (p<0.01), whereas Methods 2 (p=0.54) and 3 (p=0.63) produced consistent results across all diffusion times. Method 1 was less sensitive to detecting changes induced by MFA than Methods 2 (p<0.01) and 3 (p<0.01). Comparatively, Methods 2 and 3 proved more sensitive and generalisable; allowing for detailed assessment of the coupling between different populations of gap-junction linked cell networks.

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“…These coupled networks facilitate the rapid, lateral spread of signals across the retina that complements slower synaptic transmission. Functionally, cell-coupling between retinal neurons modulates receptive field size, facilitates the transition between photopic and scotopic retinal states and contributes to signal averaging, synchrony and motion detection [ 5 – 7 ].…”

Section: Introductionmentioning

confidence: 99%

Analytical methods for assessing retinal cell coupling using cut-loading

Myles

¹

,

McFadden²

2022

PLoS ONE

1

0

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Electrical coupling between retinal neurons contributes to the functional complexity of visual circuits. “Cut-loading” methods allow simultaneous assessment of cell-coupling between multiple retinal cell-types, but existing analysis methods impede direct comparison with gold standard direct dye injection techniques. In the current study, we both improved an existing method and developed two new approaches to address observed limitations. Each method of analysis was applied to cut-loaded dark-adapted Guinea pig retinae (n = 29) to assess coupling strength in the axonless horizontal cell type (‘a-type’, aHCs). Method 1 was an improved version of the standard protocol and described the distance of dye-diffusion (space constant). Method 2 adjusted for the geometric path of dye-transfer through cut-loaded cells and extracted the rate of dye-transfer across gap-junctions in terms of the coupling coefficient (kj). Method 3 measured the diffusion coefficient (De) perpendicular to the cut-axis. Dye transfer was measured after one of five diffusion times (1–20 mins), or with a coupling inhibitor, meclofenamic acid (MFA) (50–500μM after 20 mins diffusion). The standard protocol fits an exponential decay function to the fluorescence profile of a specified retina layer but includes non-specific background fluorescence. This was improved by measuring the fluorescence of individual cell soma and excluding from the fit non-horizontal cells located at the cut-edge (p<0.001) (Method 1). The space constant (Method 1) increased with diffusion time (p<0.01), whereas Methods 2 (p = 0.54) and 3 (p = 0.63) produced consistent results across all diffusion times. Adjusting distance by the mean cell-cell spacing within each tissue reduced the incidence of outliers across all three methods. Method 1 was less sensitive to detecting changes induced by MFA than Methods 2 (p<0.01) and 3 (p<0.01). Although the standard protocol was easily improved (Method 1), Methods 2 and 3 proved more sensitive and generalisable; allowing for detailed assessment of the tracer kinetics between different populations of gap-junction linked cell networks and direct comparison to dye-injection techniques.

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An Old Neuron Learns New Tricks: Redefining Motion Processing in the Primate Retina

Cited by 8 publications

References 10 publications

Gap junctions and connexin hemichannels both contribute to the electrical properties of retinal pigment epithelium

Gap junctions and connexin hemichannels both contribute to the electrical properties of retinal pigment epithelium

Analytical Methods for Assessing Retinal Cell Coupling Using Cut-Loading

Analytical methods for assessing retinal cell coupling using cut-loading

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