# Comprehensive quantification of cone dynamics

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $64,505

## Abstract

Cone photoreceptors in the retina mediate the vast majority of day-to-day visual percepts in
humans, and their responses represent the initial visual signals processed by downstream neurons. As a
result, characterizing the response properties of human cone photoreceptors is key to addressing gaps
in our knowledge of retinal physiology, and ultimately, the neural basis of human vison. Most studies of
mammalian cone electrophysiology have been conducted in vitro. Although this allows extensive
control, evidence suggests differences exist in cone behavior under in vivo and in vitro preparations. To
approach this issue in vivo, our lab developed a technique in which cone response properties can be
elucidated in vivo using single-cone targeted retinal stimulation with an adaptive optics scanning laser
ophthalmoscope (AOSLO) in conjunction with physiological recordings from downstream neurons.
 In addition to using normal single photon stimuli, we will utilize 2-photon stimuli to examine the
nature of direct 2-photon stimulation of cone photopigment using the AOSLO system. Though there
exists evidence suggesting direct 2-photon stimulation of cones occurs (Palczewska et al. 2014), there
remains the possibility that such percepts arise from secondary fluorescence of endogenous retinal
fluorophores. By interleaving single and 2-photon stimulation of cones, we will also be able to quantify
the differences in light capture between the two stimuli. Data gathered over the course of this project
will also be used to examine neural encoding in the optic tract and the lateral geniculate nucleus (LGN)
as it relates to psychophysical luminance threshold. Because LGN neurons receive many more spikes
than they produce, the LGN must selectively relays certain spikes (Sincich et al. 2007, Rathbun et al.
2010). How the LGN spike patterning at a given stimulus detection probability leads to perceptual
threshold is not understood, particularly in response to single cone stimulation.
 The goal of this proposal is to characterize the response properties of macaque cone photoreceptors
in vivo and determine if spike coding in retinal ganglion cells or the LGN set the bounds for human
psychophysical luminance threshold performance. In Aim 1, we will use cone-targeted stimuli to
measure cone intensity response functions, time course of recovery to a flash, and adaptation to
repeated stimuli. By incorporating 2-photon stimuli, we will quantify the extent of indirect excitation of
cones when nearby endogenous fluorophores emit light following 2-photon excitation. In Aim 2,
analysis of the spike trains recorded in Aim 1 will be used to determine how the neurometric response
function relates to psychophysical response functions. The findings of this study will address
fundamental gaps in our understanding of neural activity in the early visual system and the
mechanisms underlying 2-photon perception.

## Key facts

- **NIH application ID:** 10375224
- **Project number:** 3R01EY023603-07S1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Timothy W Kraft
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $64,505
- **Award type:** 3
- **Project period:** 2014-05-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375224

## Citation

> US National Institutes of Health, RePORTER application 10375224, Comprehensive quantification of cone dynamics (3R01EY023603-07S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10375224. Licensed CC0.

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