# Functional Divergence at the Mouse Type 6 Bipolar Cell Terminal

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2021 · $46,036

## Abstract

Project Summary
At the earliest stages of the visual system, signals diverge into separate channels, allowing for parallel processing
of visual information. In the mouse retina, 13 retinal bipolar cell types convey visual signals to ~40 retinal ganglion
cell types. Traditionally, each neuronal type was thought to convey a single channel of information; however, this
view has been challenged by evidence that retinal bipolar cells of nonmammals are able to perform subcellular
computations, enabling them to send different signals from different terminals of the same cell. Functional
divergence at the level of the synapse has not been shown in the small, relatively electrically compact bipolar
cells of the mammalian retina. My preliminary data suggests that different terminals of the same type 6 bipolar
cell can transmit different functional signals onto two different retinal ganglion cell types in the mouse. I use
confocal imaging to show anatomical connectivity between the type 6 bipolar cell and two different retinal
ganglion cells (ON alpha and PixON RGCs). To provide evidence that both the ON alpha and PixON RGCs receive
functional input from the same bipolar cell, I show that these cells have high cross correlation of physiological
noise. Using voltage clamp recordings and visual stimulation, I show that the type 6 bipolar cell provides
excitation with very little surround suppression to ON alpha RGCs but provides excitation with substantial
surround suppression to PixON RGCs. Furthermore, I show using dynamic clamp recordings and simulation of
recorded conductances that the difference in surround suppression of excitation is what drives the difference in
the receptive field properties of the two cells. To explore the circuit and cellular mechanism of this functional
divergence, I use pharmacological blockade of receptors and channels to suggest that the type 6 bipolar cell is
receiving presynaptic inhibition from a GABAergic spiking amacrine cell that is selective for those type 6 bipolar
terminals that provide input to the PixON RGC. To further investigate the anatomy of amacrine cells present at
these terminals, I will use serial electron microscopy. Finally, since glutamate release from bipolar cell terminals
is calcium dependent, I will image calcium signals from the type 6 bipolar terminals to directly observe divergence
of signals at the type 6 terminals. These findings and proposed experiments indicate that each terminal of a
single bipolar cell could potentially carry a unique visual signal. This expands the number of visual channels in
the inner retina allowing for increased parallelism at the earliest stages of visual processing.

## Key facts

- **NIH application ID:** 10146206
- **Project number:** 5F31EY030344-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** David Isaiah Swygart
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146206

## Citation

> US National Institutes of Health, RePORTER application 10146206, Functional Divergence at the Mouse Type 6 Bipolar Cell Terminal (5F31EY030344-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10146206. Licensed CC0.

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