# Functional Roles of Retinal Gap Junctions in Visual Processing

> **NIH NIH R01** · STATE COLLEGE OF OPTOMETRY · 2020 · $405,000

## Abstract

Electrical synaptic transmission via gap junctions (GJs) is an important mode of neuronal communication in the
CNS. An elegant example is the retina in which each of the five main neuronal types is electrically coupled via
GJs. The broad distribution, diverse connexin subunit structure, and regulation of retinal GJs suggest a
diversity of functional roles in visual processing; elucidating these roles forms the long-term goal of our
experimental program. Here we propose to study the GJs in the inner mouse retina, which subserve a rich and
complex variety of electrical circuits. The first aim of this proposal is to determine the role of cell-to-cell vs.
neuron ensemble interactions in creating the robust, correlated activity displayed by retinal ganglion cells
(RGCs). Correlated RGC activity is believed to have a number of functions, including enhancement of signal
saliency and encoding of specific information about visual stimuli such as intensity, size, and motion. While it is
now clear that GJs are critical to the creation of the robust concerted activity between RGC neighbors, the
exact mechanism remains unclear. While it has been posited that reciprocal drive between coupled RGC
neighbors can produce concerted firing, our preliminary data suggest that this does not occur. Rather, it
appears that coherent activity within neuronal ensembles is necessary to recruit additional RGCs and produce
their coherent activity. We propose a multidisciplinary approach combining electrophysiological,
pharmacological, and optogenetic techniques applied to transgenic and knockout mouse lines to differentiate
the circuits responsible for correlated RGC activity. The second aim will focus on the coupling between RGCs
and amacrine cells (ACs). This type of electrical coupling occurs extensively across the retina, but how this
affects neuronal activity has not been studied comprehensively due to a lack of an experimental platform to
visualize and target coupled RGC-AC pairs for recording. We will target coupled RGC-AC pairs using two
techniques: (1) labeling cells with the GJ-permenat dye Po-Pro-1; and (2) using the transgenic Grik4 mouse
line in which ON α-RGCs and coupled ACs express fluorescent markers. For both, we will record from coupled
pairs of RGCs and ACs to determine the role that this electrical interaction has on the response activity of inner
retinal neurons. In the third aim we will study the novel idea that RGCs can alter intraretinal activity by signaling
back to AC through interconnecting GJs. We posit that RGCs can alter the activity of coupled ACs, which, in
turn, inhibit other ganglion cells via conventional chemical synapses. This form of intraretinal signaling thereby
creates a circuit providing a novel form of lateral inhibition. Deficits in GJ communication have been implicated
in a number of brain neuropathies, including visual impairments associated with retinitis pigmentosa, glaucoma
and ischemic retinopathy. The experimental program pro...

## Key facts

- **NIH application ID:** 10018868
- **Project number:** 5R01EY007360-31
- **Recipient organization:** STATE COLLEGE OF OPTOMETRY
- **Principal Investigator:** Stewart Allen Bloomfield
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $405,000
- **Award type:** 5
- **Project period:** 1988-03-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018868

## Citation

> US National Institutes of Health, RePORTER application 10018868, Functional Roles of Retinal Gap Junctions in Visual Processing (5R01EY007360-31). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10018868. Licensed CC0.

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