# Dynamics of calcium signals control neurotransmitter release in retinal ribbon synapses

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2022 · $368,600

## Abstract

Retinal bipolar cells are the first 'projection neurons' of the vertebrate visual system and transmit all of the
information needed for vision. Bipolar cells can signal change in contrast while providing an analog read-out of
luminance via changing the rate of neurotransmitter release (NTR). To maintain this ability, the bipolar cells
must have dynamic control over release rate and the efficient recruitment of release-ready vesicles to fusion
sites. However, the spatiotemporal properties of Ca2+ signals that control NTR, and the molecular entities that
control the interplay between Ca2+ signal and vesicle dynamics in sustaining kinetically distinct NTR
components remain poorly understood. The long-term goal is to unveil the regulation of Ca2+ signaling in retinal
ribbon synapses during development, normal adulthood, and disease. Within this goal, the overall objective of
this proposal is to determine the spatiotemporal properties of Ca2+ signals that control kinetically distinct pools
of NTR and the role of local Ca2+ signals in governing vesicle dynamics that sustain neurotransmission in
bipolar cell ribbon synapses. The central hypothesis is that Ca2+ domains governing kinetically distinct
components of NTR are different because the ribbon itself adds an additional compartment responsible for
spatial segregation of kinetically different synaptic vesicles and the underlying molecular targets that sense
Ca2+ concentration and/or alter Ca2+ signals. This hypothesis is based on preliminary data, acquired in
applicant’s laboratory using novel techniques developed for evaluating the traffic of single synaptic vesicles at
ribbons while simultaneously measuring the underlying changes in [Ca2+], all with millisecond temporal
precision. This hypothesis will be tested by pursuing two specific aims using a confluence of state-of-the-art
fluorescence imaging, voltage-clamp electrophysiology, computational modeling, electron microscopy of
individual physiologically identified cells, and pharmacological tools: 1) Reveal the mechanisms that determine
the spatiotemporal properties of calcium signals which control kinetically distinct neurotransmitter release
pools; and 2) Determine the interplay between local calcium signaling and vesicle replenishment that is
required for sustaining kinetically distinct components of NTR in rod bipolar cell ribbon synapses as a model
system. Dysregulation of Ca2+ signaling is a key early–stage process of neurodegeneration in age-related
retinal degenerations, glaucoma, diabetic, and optic neuropathies. The knowledge gained from studying Ca2+
dynamics in bipolar cell synaptic transmission will allow us to determine if defects with local Ca2+ homeostasis
are a prelude to disease in the future. Data generated from this proposal will have a broad impact that extends
beyond our specific investigation of rod bipolar cells and will be applicable to similar ribbon synapses located
within and outside the visual system and encoding dist...

## Key facts

- **NIH application ID:** 10320486
- **Project number:** 5R01EY030863-02
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Thirumalini Vaithianathan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $368,600
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320486

## Citation

> US National Institutes of Health, RePORTER application 10320486, Dynamics of calcium signals control neurotransmitter release in retinal ribbon synapses (5R01EY030863-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10320486. Licensed CC0.

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