Posts tagged bipolar cells
Articles and news from the latest research reports.
Exploring How the Nervous System Develops
The circuitry of the central nervous system is immensely complex and, as a result, sometimes confounding. When scientists conduct research to unravel the inner workings at a cellular level, they are sometimes surprised by what they find.
Patrick Keeley, a postdoctoral scholar in Benjamin Reese’s laboratory at UC Santa Barbara’s Neuroscience Research Institute, had such an experience. He spent years analyzing different cell types in the retina, the light-sensitive layer of tissue lining the inner surface of the eye that mediates the first stages of visual processing. The results of his research are published today in the journal Developmental Cell.
Using a rodent model, Keeley and his colleagues quantified the number of cells present in each retina for 12 different retinal cell types across 30 genetically distinct lines of mice. For every cell type the team investigated, the researchers found a remarkable degree of variation in cell number across the strains. More surprising, the variation in the number of different cell types was largely independent of one another across the strains. This has substantial implications for retinal wiring during cellular development.
“These cells are connected to each other, and their convergence ratios are believed to underlie various aspects of visual processing,” Keeley explained, “so it was expected that the numbers of these cell types might be correlated. But that was not the case at all. We found very few significant correlations and even the ones we did find were modest.”
Using quantitative trait locus (QTL) analysis — a statistical method that links two types of information, in this case cell number and genetic markers — Keeley’s team compared not only the covariance between different types of cells but also the genetic co-regulation of their number. When they mapped the variation in cell number to locations within the genome, the locations were rarely the same for different types of cells. The result was entirely unexpected.
“Current views of retinal development propose that molecular switches control the alternate fates a newborn neuron should adopt, leading one to expect negative correlations between certain cell types,” said Reese, who is also a professor in UCSB’s Department of Psychological and Brain Sciences. “Still others have proposed that synaptically connected nerve cells ‘match’ their pre- and post-synaptic numbers through a process of naturally occurring cell death, leading one to expect positive correlations between connected cell types. Neither expectation was borne out.”
“If the cell types are not correlated, then some mice will have retinas with a lot of one cell type — say, photoreceptors — but not a lot of another cell type to connect to, in this case bipolar cells, or vice versa,” Keeley added. “So how does the developing retina accommodate this variation?”
The authors posit that since the ratios of pre- to post-synaptic cell number are not precisely controlled, the rules for connecting them should offer a degree of plasticity as they wire their connections during development.
Take bipolar cells as an example. To test this assumption, the scientists looked at the morphology of their dendrites, the threadlike extensions of a neuron that gather synaptic input. Keeley and coworkers examined their size, their branching pattern and the number of contacts they formed as a function of the number of surrounding bipolar cells and the number of photoreceptors across these different strains.
“We found that the extent of dendritic growth was proportional to the local density of bipolar cells,” Keeley explained. “If there are more, they grow smaller dendrites. If there are fewer, they grow larger dendrites.
“Photoreceptor number, on the other hand, had no effect upon the size of the dendritic field of the bipolar cells but determined the frequency of branching made by those very dendrites,” he added. “This plasticity in neural circuit assembly ensures that the nervous system modulates its connectivity to accommodate the independent variation in cell number.”
This research gives scientists an idea of how individual cell types are generated, how they differentiate and how they form appropriate connections with one another. Researchers in the Reese lab are trying to understand the genes that control these processes.
“I think that’s important when we discuss cellular therapeutics such as transplanting stem cells to replace cells that are lost,” Keeley said. “We’re going to need this sort of fundamental knowledge about neural development to promote the differentiation and integration of transplanted stem cells. This focus on genetic and cellular mechanisms is going to be important for developing new therapies to treat developmental disorders affecting the eye.”
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.
The end of a dogma: Bipolar cells generate action potentials
To make information transmission to the brain reliable, the retina first has to “digitize” the image. Until now, it was widely believed that this step takes place in the retinal ganglion cells, the output neurons of the retina. Scientists in the lab of Thomas Euler at the University of Tübingen, the Werner Reichardt Centre for Integrative Neuroscience and the Bernstein Center Tübingen were now able to show that already bipolar cells can generate “digital” signals. At least three types of mouse BC showed clear evidence of fast and stereotypic action potentials, so called “spikes”. These results show that the retina is by no means as well understood as is commonly believed.
The retina in our eyes is not just a sheet of light sensors that – like a camera chip – faithfully transmits patterns of light to the brain. Rather, it performs complex computations, extracting several features from the visual stimuli, e.g., whether the light intensity at a certain place increases or decreases, in which direction a light source moves or whether there is an edge in the image. To transmit this information reliably across the optic nerve - acting as a kind of a cable - to the brain, the retina reformats it into a succession of stereotypic action potentials – it “digitizes” it. Classical textbook knowledge holds that this digital code – similar to the one employed by computers – is applied only in the retina’s ganglion cells, which send the information to the brain. Almost all other cells in the retina were believed to employ graded, analogue signals. But the Tübingen scientists could now show that, in mammals, already the bipolar cells, which are situated right after the photoreceptors within the retinal network, are able to work in a “digital mode” as well.
Using a new experimental technique, Tom Baden and colleagues recorded signals in the synaptic terminals of bipolar cells in the mouse retina. Based on the responses of these cells to simple light stimuli, they were able to separate the neurons into eight different response types. These types closely resembled those expected from physiological and anatomical studies. But surprisingly, the responses of the fastest cell types looked quite different than expected: they were fast, stereotypic and occurred in an all-or-nothing instead of a graded fashion. All these are typical features of action potentials. Such “digital” signals had occasionally been observed in bipolar cells before, but these were believed to be rare exceptional cases. Studies from the past two years on the fish retina had already cast doubt on the long-held belief that BCs do not spike. The new data from Tübingen clearly show that these “digital” signals are systematically generated in certain types of mammalian bipolar cells. Action potentials allow for much faster and temporally more precise signal transmission than graded potentials, thus offering advantages in certain situations. The results from Tübingen call a widely held dogma of neuroscience into question - and open up many new questions.