Modeling cell connections in the retina

With 576-megapixel resolution, our eyes are incredible cameras, capturing 72-times more high-definition detail than the iPhone 6. To do this, our retinas are packed with many different cell types that help transmit light information to the brain. We know very little, however, about how these cells interconnect, so researchers have turned to mapping and tracing how one cell connects with another…and you can help. A team of scientists at MIT has developed an online game called EyeWire that allows anyone to figure out how cells connect in the retina with real science implications. This image was generated from players correctly tracing connections from one cell to the next, generating a complete connectivity map for these seven cells.

Image by Amy Robinson, Alex Norton, Sebastian Seung, William Silversmith, Jinseop Kim, Kisuk Lee, Aleks Zlasteski, Matt Green, Matthew Balkam, Rachel Prentki, Marissa Sorek, Celia David, Devon Jones, and Doug Bland.

Wiring of retina reveals how eyes sense motion

Online gamers helped researchers map neuron connections involved in detecting direction of moving objects.

A vast project to map neural connections in the mouse retina may have answered the long-standing question of how the eyes detect motion. With the help of volunteers who played an online brain-mapping game, researchers showed that pairs of neurons positioned along a given direction together cause a third neuron to fire in response to images moving in the same direction.

It is sometimes said that we see with the brain rather than the eyes, but this is not entirely true. People can only make sense of visual information once it has been interpreted by the brain, but some of this information is processed partly by neurons in the retina. In particular, 50 years ago researchers discovered that the mammalian retina is sensitive to the direction and speed of moving images. This showed that motion perception begins in the retina, but researchers struggled to explain how.

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The human eye can see ‘invisible’ infrared light

Any science textbook will tell you we can’t see infrared light. Like X-rays and radio waves, infrared light waves are outside the visual spectrum. But an international team of researchers co-led by scientists at Washington University School of Medicine in St. Louis has found that under certain conditions, the retina can sense infrared light after all.

Using cells from the retinas of mice and people, and powerful lasers that emit pulses of infrared light, the researchers found that when laser light pulses rapidly, light-sensing cells in the retina sometimes get a double hit of infrared energy. When that happens, the eye is able to detect light that falls outside the visible spectrum.

"We’re using what we learned in these experiments to try to develop a new tool that would allow physicians to not only examine the eye but also to stimulate specific parts of the retina to determine whether it’s functioning properly," said senior investigator Vladimir J. Kefalov, PhD, associate professor of ophthalmology and visual sciences at Washington University. "We hope that ultimately this discovery will have some very practical applications."

The eye can detect light at wavelengths in the visual spectrum. Other wavelengths, such as infrared and ultraviolet, are supposed to be invisible to the human eye, but Washington University scientists have found that under certain conditions, it’s possible for us to see otherwise invisible infrared light. Credit: Sara Dickherber

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Filled half the page as a warmup before work and the half after work as a cool down. Tried out the toned gray Strathmore this time. Bic ballpoint pen(round Stic M) some colerase, and a streaky white pen the refused to cooperate.
#battleberzerkerbalto #sketches #art #ink #5kRetinaMacIsPrettySweetBTW #apple #imac #retina #wow #hehshtegs #heh #pewpewpew

08 May 2014

Rainbow Retina

Zebrafish embryos are transparent, making them ideal for studying the formation of complicated cell tissue such as the eyes and the brain. Researchers are currently using a ‘spectrum of fates’ approach in order to learn more about the development of the retina – optical tissue which lines the inside of eyes and communicates with the brain. This technique uses specifically tuned fluorescent proteins to colour-code different cell types. The fluorescent proteins are injected into the yolk of an early-stage zebrafish embryo, where they will track the five major retinal cell types, causing them to fluoresce in a specific colour. Taking images of the retina during its development (pictured) allows the structural formation to be studied in real time – cells can be followed from birth, and around any paths they take before settling into place. Studies like this will improve our understanding of how biological structures initiate and grow.

Written by Helen Thomas

Image by William Harris and colleagues
University of Cambridge, UK
Originally published under a Creative Commons Licence
Research published in Development, April 2014

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(Image caption: When a zebrafish larva sees a prey object, this information is sent to neurons in the AF7 region of the brain. These neurons (one of which is shown here in blue) then send the hunting impulse to the areas that control movement. Credit: © MPI of Neurobiology/ Semmelhack)

Which dot will they hunt?

Seeing – recognising – acting. These three words describe how a sensory input can lead to a targeted movement. However, very little is known about how and where the brain converts external inputs into behavioural responses. Now, scientists at the Max Planck Institute of Neurobiology in Martinsried have been able to shed light on important neural circuitry involved in the prey capture behaviour exhibited by young zebrafish. The findings show that neurons in the retina of the eye already filter out prey objects from other environmental signals. The cells then forward this information to an area of the brain, which, up to now, had no identifiable role. The corresponding swimming movements are then initiated here.

It’s not easy to catch a ball. The ball must first be recognised and tracked by the eyes. At the same time, the body’s own movements must be coordinated in such a way that the hands hang on to the ball at the right time and in the right place. For animals, such coordination of visual inputs and their own movements is critical to their survival: it is only in this way that they can recognise, track and catch prey. For many animals, fundamental prey capture behaviour is therefore innate. Up until now, scientists could not explain how and where the brain recognises and classifies an object and initiates the corresponding movement pattern.

Prey causes the fish brain to light up

As soon as they are hatched, zebrafish larvae can already hunt single-celled organisms such as paramecia. The brain of the tiny fish is able to recognise the single-celled organism as a target, calculate its location and steer its body towards the prey using characteristic tail movements. This innate prey capture behaviour can also be triggered in the laboratory using small, moving dots. Scientists can thus present potential “prey” on a miniature screen and study the subsequent processes in the fish brain – as zebrafish larvae are almost transparent. As a result of genetic modifications, the neurons in the fish brain that are active at a given moment light up in the transparent brain. Processes in the fish brain can therefore be observed using a microscope while the animals recognise and classify their prey and swim towards them.

To understand the neural circuits of the prey capture behaviour, the neurobiologists initially concentrated on the recognition of prey objects. “First of all, we looked at the connections between the retina and the brain,” says Julia Semmelhack, describing her work. Neurons in the zebrafish retina project into 10 areas in the brain known as AF regions; however, very little is known about the role of these regions. The scientists in Martinsried were able to show that the neurons in one of these 10 AF regions always became active when the dots shown fitted the brain’s template of an optimal prey object. Larger or smaller dots had no effect. The AF7 brain region lit up only in the presence of virtual dots that were the “right” size (and in the case of actual paramecia).

A brain region reveals itself

Further investigation showed that the neurons in the retina filter out potential prey objects from the environment. The information is only sent to the AF7 region if a dot is the “right” one. From there, the hunting impulse is then sent to other visual regions and to the areas controlling movement. When the scientists cut the AF7 connections, the fish responded only to a very limited extent to the dots representing the prey.

The AF7 region is therefore essential for classifying visual stimuli as prey and for triggering the associated hunting behaviour. “We have shown how a visual signal from the retina, travelling via the AF7 region, leads to certain behaviour,” says a delighted Herwig Baier, who, together with his department at the Max Planck Institute of Neurobiology, is studying how sensory inputs from the brain are converted into behavioural responses. A major first step has been taken. The neurobiologists now want to find out how the information in the AF7 region is translated into the various swimming movements.

Nanotubes may restore sight to blind retinas

The aging process affects everything from cardiovascular function to memory to sexuality. Most worrisome for many, however, is the potential loss of eyesight due to retinal degeneration.

New progress towards a prosthetic retina could help alleviate conditions that result from problems with this vital part of the eye. An encouraging new study published in Nano Letters describes a revolutionary novel device, tested on animal-derived retinal models, that has the potential to treat a number of eye diseases. The proof-of-concept artificial retina was developed by an international team led by Prof. Yael Hanein of Tel Aviv University’s School of Electrical Engineering and head of TAU’s Center for Nanoscience and Nanotechnology and including researchers from TAU, the Hebrew University of Jerusalem, and Newcastle University.

Lilach Bareket, Nir Waiskopf, David Rand, Gur Lubin, Moshe David-Pur, Jacob Ben-Dov, Soumyendu Roy, Cyril Eleftheriou, Evelyne Sernagor, Ori Cheshnovsky, Uri Banin, Yael Hanein. Semiconductor Nanorod–Carbon Nanotube Biomimetic Films for Wire-Free Photostimulation of Blind Retinas. Nano Letters, 2014; 14 (11): 6685 DOI: 10.1021/nl5034304

We report the development of a semiconductor nanorod-carbon nanotube based platform for wire-free, light induced retina stimulation. A plasma polymerized acrylic acid midlayer was used to achieve covalent conjugation of semiconductor nanorods directly onto neuro-adhesive, three-dimensional carbon nanotube surfaces. Photocurrent, photovoltage, and fluorescence lifetime measurements validate efficient charge transfer between the nanorods and the carbon nanotube films. Successful stimulation of a light-insensitive chick retina suggests the potential use of this novel platform in future artificial retina applications.

The Social Psychology of Nerve Cells

The functional organization of the central nervous system depends upon a precise architecture and connectivity of distinct types of neurons. Multiple cell types are present within any brain structure, but the rules governing their positioning, and the molecular mechanisms mediating those rules, have been relatively unexplored.

A new study by UC Santa Barbara researchers demonstrates that a particular neuron, the cholinergic amacrine cell, creates a “personal space” in much the same way that people distance themselves from one another in an elevator. In addition, the study, published in the Proceedings of the National Academy of Sciences, shows that this feature is heritable and identifies a genetic contributor to it, pituitary tumor-transforming gene 1 (Pttg1).

Patrick Keeley, a postdoctoral scholar in Benjamin Reese’s laboratory at UCSB’s Neuroscience Research Institute, has been using the retina as a model system for exploring such principles of developmental neurobiology. The retina is ideal because this portion of the central nervous system lends itself to such spatial analysis. 

“Populations of neurons in the retina are laid out in single strata within this layered structure, lending themselves to accurate quantitation and statistical analysis,” explained Keeley. “Rather than being distributed as regular lattices of nerve cells, populations in the retina appear to abide by a simple rule, that of minimizing proximity to other cells of the same type. We would like to understand how such populations create and maintain such spacing behavior.”

To address this, Keeley and colleagues quantified the regularity in the population of a particular type of amacrine cell in the mouse retina. They did so in 26 genetically distinct strains of mice and found that every strain exhibited this same self-spacing behavior but that some strains did so more efficiently than others. Amacrine cells are retinal interneurons that form connections between other neurons and regulate bipolar cell output.

“The regularity in the patterning of these amacrine cells showed little variation within each strain, while showing conspicuous variation between the strains, indicating a heritable component to this trait,” said Keeley.

“This itself was something of a surprise, given that the patterning in such populations has an apparently stochastic quality to it,” said Reese, a professor in the Department of Psychological and Brain Sciences. Stochastic systems are random and are analyzed, at least in part, using probability theory.

This strain variation in the regularity of this cellular patterning showed a significant linkage to a location in the genome on chromosome 11, where the researchers identified Pttg1, previously unknown to play any role in the retina.

Working in collaboration with colleagues at the University of Tennessee Health Science Center in Memphis, Keeley’s team demonstrated that the expression of this gene varies across the 26 strains of mice and that there was a positive correlation between gene expression and regularity. They then identified a mutation in this gene that itself correlated with expression levels and with regularity. Working with colleagues at Cedars-Sinai Medical Center in Los Angeles, the team also demonstrated directly that this mutation controlled gene expression.   

“Pttg1 has diverse functions, being an oncogene for pituitary tumors, and is known to have regulatory functions orchestrating gene expression elsewhere in the body,” explained Keeley. “Within this class of retinal neurons, it should be regulating the way in which cells integrate signals from their immediate neighbors, translating that information to position the cell farthest from those neighbors.” Future studies should decipher the genetic network controlled by Pttg1 that mediates such nerve-cell spacing.

22 July 2014

Retinal Restoration

There’s currently no cure for retinitis pigmentosa (RP), a group of inherited eye diseases that impair the retina’s ability to respond to light, resulting in gradual loss of vision. But now, researchers have used stem cells to develop a promising experimental treatment. First they reprogrammed skin cells from RP patients into stem cells to make patient-specific retinal cells for closer inspection. They found that mutations in a gene called MFRP disrupt the production of actin (red), a protein that provides scaffolding for retinal cells. When this structure doesn’t form properly (left), retinal cells don’t work very well. But when the team used a virus to smuggle in a working copy of MFRP, the structure was restored (right). And in mice with an RP-like condition, the treatment slowly improved vision. It’s early days yet but these results show how patient-specific stem cells can kick start the development of tailor-made therapies.

Written by Daniel Cossins

Image by Stephen Tsang and colleagues
Columbia University Medical Center, USA
Originally published under a Creative Commons Licence (BY 4.0)
Research published in Molecular Therapy, July 2014

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