Confocal image of a layer 2/3 pyramidal cell (red) and its local presynaptic network (green).



July 03, 2015

Smart viruses enlighten vision in the brain

Botond Roska and his group at the Friedrich Miescher Institute for Biomedical Research (FMI) have provided novel insights into the functioning of neuronal networks in the visual cortex. For the first time, they were able to measure the neuronal activity during visual stimulation of an individual cortical neuron together with the network of neurons that connect to it. Their results and the discovery of two modes of network functioning have been published today in Science.

Whatever we see is a collection of shapes, corners, edges, differences in contrast and color, and motion in different directions. In the retina, these qualities are fanned-out and different sets of neurons become active. The information is then transmitted to the brain, in particular the visual cortex, where it is further processed to produce the images that we perceive.

Already in the late 1950s scientists found that neurons in the primary visual cortex also respond specifically to distinct environmental features such as direction of visual motion and the orientation of edges. How this clear-cut selectivity is achieved has been a longstanding puzzle in the field.

Adrian Wertz and Stuart Trenholm, two postdoctoral fellows in Botond Roska’s group at the Friedrich Miescher Institute for Biomedical Research (FMI) have been able to provide insights into this problem. In a study published today in Science, they have not only been able to identify the several hundred neurons that are directly connected to an individual neuron in the primary visual cortex, but have also been able to measure their activities upon visual stimulation.

Using the latest transsynaptic viral tracers equipped with genetically encoded sensors in combination with in vivo two-photon imaging, the scientists measured the visual responses of individual cells in layer 2/3 of the visual cortex as well as responses from approximately a hundred other cortical cells that provide input to them. “A particularly well-established visual response to study is the activity of neurons associated with motion,“ explained Wertz. “Neurons in the visual cortex respond rather specifically to motion. They may be active as the object moves in one direction, and inactive as soon as the motion shifts into another direction.” Using this model system, the scientists showed that neurons within each cortical layer exhibited similar motion direction preferences, forming what they called ‘layer modules’. Sometimes these preferences were aligned across layers, in other cases, the preferences varied by layer. “Interestingly the visual cortex uses at least two types of networks and some of these networks are aligned from layer module to layer module, while others are variant,” commented Trenholm. And Roska added: “We still don’t know why this is the case. Perhaps the more variant networks are more plastic and learning could force them into a more locked state. We have to test this hypothesis in the future.”

Now for the first time neuroscientists have the tools at hand to not only make neuronal networks visible and describe them but also to measure the neuronal activity of individual cells and the networks that connect to them. “This is an important step for us to understand what is computed within the cortex and what is inherited from the retina,” commented Roska, “and when these tools are applied to other brain areas they will provide novel insights into how the brain is functionally wired.“

Original publication
Wertz A, Trenholm S, Yonehara K, Hillier D, Raics Z, Leinweber M, Szalay G, Ghanem A, Keller G, Rózsa B, Conzelmann K-K, Roska B. (2015) Single-cell-initiated monosynaptic tracing reveals layer-specific cortical network modules. Science 349:70-74

More about Botond Roska
Botond Roska is interested in how neurons interact in local neuronal networks to compute behaviorally relevant functions. He studies these processes in the mammalian retina, thalamus and visual cortex. He has also done research into retinitis pigmentosa, a rare disease that leads to blindness. In the course of these experiments he has been able to identify a novel approach to treat the disease.
» More about Botond Roska

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