# Synapses as Independent Computational Units in the Excitatory Pathways of the Retina

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $395,000

## Abstract

Project Summary/Abstract
Determining the computational units of a neuronal circuit is essential in understanding the function of the circuit
as a whole. In many circuits, subcellular compartmentalization allows synaptic boutons on the presynaptic side,
and dendrites, on the post-synaptic side, to functional independently. In sensory systems, functional
divergence allows enabled the representation of many features of a stimulus using a limited number of
neurons. The retina is an advantageous model system for studying synaptic mechanism of circuit motifs, like
functional divergence, because our advanced knowledge of cell types and circuit architecture in the retina
allows us to ask precise questions about connectivity and function in response to visual stimuli.
In the mouse retina, signals diverge from two cone types to ~15 bipolar cell (BC) types, and then to > 40 retinal
ganglion cell (RGC) types at the output level. Mechanisms for functional divergence are well established at the
first synapse in the retina, but much less is known about mechanisms at the second synapse, from BCs to
RGCs. My work will fill this gap by establishing a model system in which a single BC type diverges to provide
functionally distinct input to two different RGC types. The core hypothesis of this project is that different
synapses from the same BC can act as independent computational units, relaying different patterns of
glutamate release to their postsynaptic partners.
In Aim 1, we will obtain physiological evidence that these two RGC types share input from different synapses
on the same BCs. In Aim 2, we will measure the ultrastructure of the synapses with electron microscopy to
determine the role of postsynaptic RGC identity on the structure of the BC synapses. In Aim 3, we will
demonstrate functional compartmentalization within the BC terminal, first with an electrotonic modeling
approach, and then with experimental measurements of glutamate release.
The successful completion of this project will resolve the question of whether individual BCs can transmit
functionally distinct glutamate signals from different synapses. Confirmation of functional divergence at the
level of BC synapses will alter our picture of the computational structure of retinal circuits. Instead of
considering bipolar cells as the computational units of excitation, we will instead show that bipolar cell output
synapses can perform independent computations. This paradigm change will have important consequences for
models of retinal circuits, and it will open up new areas of study into the molecular determinants of subcellular
wiring specificity in development.

## Key facts

- **NIH application ID:** 9863634
- **Project number:** 1R01EY031029-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Gregory William Schwartz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $395,000
- **Award type:** 1
- **Project period:** 2020-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9863634

## Citation

> US National Institutes of Health, RePORTER application 9863634, Synapses as Independent Computational Units in the Excitatory Pathways of the Retina (1R01EY031029-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9863634. Licensed CC0.

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