# Regulation of Photoreceptor Neurotransmisssion

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $410,722

## Abstract

Light responses of rod and cone photoreceptors are encoded by the release of glutamate-filled vesicles at
photoreceptor synapses. Synaptic transmission at the first synapse in the retina thus fundamentally shapes
visual perception and damage to photoreceptor synapses by protein mutation or diseases such as macular
degeneration and ischemia causes vision loss. To understand the consequences of damage to these synapses
and how to restore vision by therapeutic means requires a thorough understanding of their normal operation.
Release from photoreceptors involves a plate-like protein structure known as the synaptic ribbon. Unlike most
central nervous system (CNS) synapses that release only one or two synaptic vesicles at a time, ribbon synapses
in photoreceptors and other sensory neurons are specialized for continuous release. In addition to the ribbon
itself, the specialized capabilities of ribbon synapses are also determined by the use of certain proteins that
differ from those at more conventional synapses. Rod and cone photoreceptors differ further from both
conventional and other ribbon synapses in their use of an exocytotic Ca2+ sensor with unusual Ca2+
dependence. At most synapses, synaptic vesicle release rate rises with the 5th power of [Ca2+]i but release from
photoreceptors has a weaker 1-3rd order Ca2+-dependence. The identity of the atypical Ca2+ sensor that
regulates vesicle release from photoreceptors is a major unresolved question about the mechanisms of release
at the first synapse in the retina. Isoforms of the protein synaptotagmin (Syt) serve as the exocytotic Ca2+
sensors in most neurons. Our first aim is to identify the Ca2+ sensor controlling release from photoreceptors by
testing mice in which specific Syt proteins have been selectively deleted from rods or cones. Our second aim is
to confirm that the exocytotic Ca2+ sensors in mouse rod and cone synapses retain the unusually low Ca2+
cooperativity seen in lower vertebrates. In Aim 3, we propose to characterize how the Ca2+-dependence of
release rate is shaped by different combinations of Syt, Complexin, and SNARE proteins that reproduce
components of the rapid release machinery at different conventional and ribbon synapses, using unique in
vitro approaches that can probe single fusion pores with sub-ms time resolution. Together, these experiments
will reveal the mechanisms responsible for the atypical Ca2+-dependence of neurotransmission at the critical
first synapse in vision and allow us to understand how the expression of particular proteins shapes the
properties of release to meet specific signaling needs at different CNS synapses.

## Key facts

- **NIH application ID:** 10085227
- **Project number:** 5R01EY010542-25
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** ERDEM KARATEKIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $410,722
- **Award type:** 5
- **Project period:** 1996-06-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085227

## Citation

> US National Institutes of Health, RePORTER application 10085227, Regulation of Photoreceptor Neurotransmisssion (5R01EY010542-25). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10085227. Licensed CC0.

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