Colloquially, the eyes are the window to the soul. Biologically, they may be the key to enhancing scientific understanding of the brain’s neural circuits.
At an event co-sponsored by the German Center for Research and Innovation and the Max Planck Florida Institute, Joshua Sanes, a member of the Dana Alliance for Brain Initiative and professor at Harvard University, and David Fitzpatrick, scientific director and CEO of the Max Planck Florida Institute, explained their research into the circuitry of the retina and the visual cortex.
Their research brings into focus the roles genetics and environment play in shaping neural circuitry.
As Dr. Sanes explained, the retina is complicated but compact, making it “a playground for figuring out how circuits work.” Three layers of cells make up the retina: photoreceptors, which sense light; interneurons, which process information between the layers; and retinal ganglion cells, which respond to movement, orientation, color contrast, and edges. There are at least 50 types of interneurons and retinal ganglion cells, and only a few connect to each other, forming parallel pathways for communicating visual information.
Using a fluorescent protein, Sanes’ lab marked the gene Jam-B, which only appears in a small number of mouse retinal ganglion cells. They found that the dendrites of these cells all had the same orientation, and that the axons all pointed toward the center of the retina. They all respond to motion moving in the direction of their dendrites.
Stained Jam-B RGC dendrites pointing in the same direction, with axons going toward the center of the retina. (Credit: In-Jung Kim and Joshua Sanes, 2008)
“It’s rare that you can determine function from structure,” said Sanes. But these cells—and at least nine other types of retinal ganglion cells now identified by scientists—are genetically hard-wired to respond to particular directions of motion.
In contrast, said Fitzpatrick, experience can shape the responses of cells and circuits in the visual cortex.
Using two-photon in vivo microscopy, an imaging technique that allows researchers to study brain activity in living animals, Fitzpatrick looked at direction-selectivity emergence in individual neurons in the ferret cortex. Ferrets are not born with direction-selective cortical cells—there is a critical window for their development soon after birth.
Fitzpatrick and his colleagues presented visually naïve ferrets with a motion stimulus while recording their neuronal activity. After eight to ten hours of training, direction signals correlating to the direction of the stimulus began to form. “Experience was driving circuit emergence,” said Fitzpatrick.
Some cortical cells do show a weak bias toward one direction over another when shown a bidirectional object; there may be some genetic-experience interaction at play. Still, no one yet knows why experience molds cortical cells, while genetics alone drives retinal cells. But clearly, the imaging techniques now available to neuroscientists—like two-photon microscopy and fluorescent proteins—will help answer these questions while unraveling the brain’s neural circuitry.