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Always Something to Learn

Posted by Ilena Di Toro | Posted on February 20, 2024

Studying nonhuman eye tissue can lead to insight into how vision develops and the mechanisms that make vision possible. Sometimes, this research leads to new tools or it uncovers novel cellular processes in the eye. Two research projects, one at New York University (NYU) discovered new cells types in the visual system of fruit flies, and another at Northwestern University Feinberg School of Medicine, studied non-human mammalian retinas to learn more about cone synapses inside the retina.

Scientists in the lab of Claude Desplan, the Silver Professor of Biology and Neural Science at NYU, discovered new cell types in the visual system of fruit flies. Earlier research done in his lab, using single-cell sequencing, found that there are up to 200 cell types in the developing fruit fly’s visual system. Single-cell sequencing shows gene expression, so when the genes have the same expression pattern, that means they are doing the same thing and are the same cell type. While they could identify almost half of the 200 cell types in the fruit fly’s visual system, they didn’t have a way to study and label the other half of the cell types. They needed something to study cells in the fruit fly’s developing brain.

Yu-Chieh David Chen, a postdoctoral associate at NYU’s Department of Biology, created a tool that takes advantage of the single-cell sequencing data to identify genes that are expressed in certain kinds of cells. The tool looked for two genes that overlap. Researchers submitted single-cell RNA sequencing data into an algorithm they created. As a result of the algorithm, the researchers were able to identify pairs of genes specifically expressed in most of the cell types in the fruit fly’s visual system at different stages of development. Consequently, they discovered a new cell type called MeSps. Thanks to this new tool, scientists will learn more about the function of the MeSps cell in future research.

This tool distinguishes the different kinds of cell in fruit flies and allows scientist to better understand neural circuit development and function. What also makes this algorithm a good tool is that it looks for gene pairs instead of a single gene marker, making it usable with other animals and for studying other biological systems aside from vision in the developing fruit fly.

Now, for the study about the cone synapses inside the retina conducted at Northwestern University Feinberg School of Medicine. It found novel cellular mechanisms within the retina. Scientists, led by Steven DeVries, MD, PhD, the David Shoch, MD, PhD, Professor of Ophthalmology, used super-resolution microscopes to map the locations of the transmitter release sites, transmitter re-uptake proteins and post-synaptic contacts at the cone synapse. Next, they did something they called “synaptic accounting,” to connect to the amount of transmitters released by the cone to the responses in each post-synaptic bipolar cell type. Since most synapses involve one-to-one contact across a narrow space, it is presumed that one detected quantum is equal to one released quantum. (A quantum is a discrete measure of energy or matter.)

The cone synapse design cancels out this assumption, so the scientists developed a way to stimulate a cone and count the vesicles that are released while also counting the number of vesicles that are detected by the postsynaptic neuron. Using these techniques, scientists were able to show that certain cell types respond to individual fusion events and total quanta, while other cell types respond to different levels of locally coincident events. The differences are caused by a combination of factors particular to each cell type, such as diffusion distance, contact number, just to name a few.

“The outer retina uses the same toolbox as elsewhere in the central nervous system, like vesicles, synaptic release zones and postsynaptic receptors, but organizes these elements in novel ways to accomplish a different, very localized type of processing,” said DeVries. The next step in this research is to use more powerful microscopes to the learn about the protein components that consist of the cone synapses. For example, some cells are very sensitive to small signals and other require strong signals to respond. The cells that respond to strong signals have a special type of receptor that DeVries calls “insensitive post-synaptic” and he would like to further identify this receptor.

Whether subject is the fruit fly or mammalian eye tissue, there’s always something to new to discover when it comes to vision. As scientists probe further into these findings, research has the potential to find the answers to the questions that surround the world of sight.


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