# Physiology of Photoreceptors

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $351,000

## Abstract

PROJECT SUMMARY/ABSTRACT
The signals of rods and cones set the fundamental limits of visual discrimination, which ultimately determine
our ability to detect objects in the world around us. Normal photoreceptor function is essential for vision;
degeneration of rods and cones produces blindness. Although research during the last 40 years has clarified
many features of photoreceptor function and dysfunction, most of this work has been done on rods, even
though cones respond over a much wider range of intensities and are more important in visual perception,
particularly for the ability of the visual system to detect change and motion. The principal aim of this proposal
is to exploit an important technical advance which, for the first time, has made possible the routine recording
of both voltage and current light responses from intact mouse cones. Although cones in other mammalian
species including primates have been investigated, mouse has the particular advantage that mutant strains are
available. These strains make possible (1) more accurate voltage clamping of photoreceptors by removal of
photoreceptor gap junctions, (2) deletion of particular conductance mechanisms to test their effects on signal
modulation and degeneration, and (3) physiological recording from degenerating cones in strains particularly
amenable to analysis. With these techniques, we are proposing to learn how cone inner-segment conductances
modulate outer-segment currents to generate voltage responses and increase temporal discrimination.
Recordings will be made from Cx36-/- mutant mice lacking connexin-36 gap junctions, and from Cx36-/- mice
also lacking one of the inner-segment conductances, in order to explain how these conductances interact with
outer-segment currents to produce the waveform of voltage responses. We will use a combination of white
noise and chirp stimuli to investigate the temporal characteristics of cone responses, in order to assess the
importance of inner-segment conductances to the frequency response of the cone. We will use mathematical
modeling to explain the effects of each of the inner-segment conductances on the waveform of the voltage
response and on temporal sensitivity. Our ultimate goal is to understand how inner-segment conductances
shape the voltage response and determine the sensitivity of cones to changing illumination. We will use these
same techniques to investigate how cone function is altered during degeneration. We are proposing to record
from cones at several stages during degeneration in both rd10 and Cngb1-/- mice, whose cones degenerate at
different rates. In this way, we hope to study cone single-cell physiology as they begin losing their outer
segments, and then later from single "dormant" cell bodies after outer segments are lost. We will also
investigate the effect of deletion of inner-segment conductances on the rate of cone degeneration, and the effect
of these deletions on the physiology of the degenerating cells.

## Key facts

- **NIH application ID:** 10364441
- **Project number:** 2R01EY001844-45A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** GORDON Lee FAIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $351,000
- **Award type:** 2
- **Project period:** 1984-07-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364441

## Citation

> US National Institutes of Health, RePORTER application 10364441, Physiology of Photoreceptors (2R01EY001844-45A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10364441. Licensed CC0.

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