# Function of Basal Synapses at Mammalian Photoreceptors

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $383,150

## Abstract

The long-term objective of this project is to understand how the unique structure of the mammalian cone
photoreceptor synapse determines its function in vision. The opsin proteins in the outer segments of cones
convert absorbed light into a voltage signal. In a necessary step for visual perception, the voltage signal
spreads to the photoreceptor synaptic terminal where it gates a Ca2+ channel that controls the release of the
transmitter glutamate onto postsynaptic bipolar and horizontal cells. Parallel processing in the visual system
begins at the cone synapse. Each cone terminal communicates with ~14 anatomically distinct bipolar cell
types at two structurally unique contacts termed invaginating and basal. Transmitter is not released at basal
contacts, but instead at sites near the top of each of a cone's 20-40 invaginations. Released glutamate must
then diffuse over an extracellular path of 200 – 500 nm to reach the dendrites of basally contacting bipolar cells.
Recent results suggest that a long diffusion path can introduce a threshold that eliminates the low-amplitude
noise associated with random fluctuations in cone transmitter release in the dark. At the same time, the
threshold permits the cone to transmit signals resulting from larger release events coordinated by a change in
illumination. Using electro- and opto-physiological techniques, this proposal addresses two mechanisms that
increase the threshold nonlinearity at basal contacts: First, at least one type of Off bipolar cell expresses
receptors with an unusually high EC50 for glutamate (~1.5 mM); and second, basally located glutamate
transporters provide saturable binding sites that can deplete cleft glutamate under dark release conditions.
Specific Aim 1 addresses the mechanisms and functions of the threshold nonlinearity at the cone to cb1a
bipolar cell basal synapse. Experiments will determine how transporter glutamate binding and kainate receptor
properties contribute to nonlinear signal transmission during a light stimulus. Specific Aim 2 focuses on the
“nano-scopic” spatial localization of the proteins that shape transmission at the cone synapse. This aim uses a
newly developed “thick slab” superresolution imaging technique to relate the cone synapse nanostructure to its
response properties. Information about the properties of cone transmitter release, glutamate transporters, and
postsynaptic receptors will be combined with localization information obtained from superresolution microscopy
to create a functional model of the basal synapse. In addition to responding to membrane voltage, it is
becoming increasingly clear that Ca2+ channels in the cone terminal integrate modulatory inputs from other
sites in the retina including from horizontal cells. Blue or short wavelength-sensitive (S-) cones are unique
among the photoreceptor types in expressing S-opsin both in the outer segment and at the synaptic terminal.
Recent experiments show that when activated by light, terminal S-opsi...

## Key facts

- **NIH application ID:** 10178029
- **Project number:** 5R01EY012141-24
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Steven H DeVries
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $383,150
- **Award type:** 5
- **Project period:** 1999-01-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10178029

## Citation

> US National Institutes of Health, RePORTER application 10178029, Function of Basal Synapses at Mammalian Photoreceptors (5R01EY012141-24). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10178029. Licensed CC0.

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