Study Reveals Unexpected Details About Visual Connections in Brain, Overturning Textbooks

Using a technique dubbed “brainbow,” the Virginia Tech Carilion Research Institute scientists tagged synaptic terminals with proteins that fluoresce different colors. The researchers thought one color, representing the single source of the many terminals, would dominate in the clusters. Instead, several different colors appeared together, intertwined but distinct. Image: Virginia Tech

Roanoke, VA (Scicasts) — Neuroscientists know that some connections in the brain are pruned through neural development. Function gives rise to structure, according to the textbooks. But scientists at the Virginia Tech Carilion Research Institute have discovered that the textbooks might be wrong.

Their results were published today (Aug. 27) in Cell Reports.

“Retinal neurons associated with vision generate connections in the brain, and as the brain develops it strengthens and maintains some of those connections more than others. The disused connections are eliminated,” said Michael Fox, an associate professor at the Virginia Tech Carilion Research Institute who led the study.

“We found that this activity-dependent pruning might not be as simple as we’d like to believe.”

Fox and his team of researchers used two different techniques to examine how retinal ganglion cells – neurons that live in the retina and transmit visual information to the visual centers in the brain – develop in a mouse model.

“It’s widely accepted that synaptic connections from about 20 retinal ganglion cells converge onto cells in the lateral geniculate nucleus during development, but that number reduces to just one or two by the third week of a mouse’s life,” Fox said.

“It was thought that the mature retinal ganglion cells develop several synaptic terminals that cluster around information exchange points.”

The theory of several terminals blossoming from the same retinal ganglion cell had not been proved, though, so Fox and his researchers decided to follow the terminals to their roots.

Using a technique dubbed “brainbow,” the scientists tagged the terminals with proteins that fluoresce different colors. The researchers thought one color, representing the single source of the many terminals, would dominate in the clusters. Instead, several different colors appeared together, intertwined but distinct.

“The samples showed a true ‘brainbow,’” said Aboozar Monavarfeshani, a graduate student in Fox’s laboratory who tagged the terminals. “I could see, right in front of me, something very different than the concept I learned from my textbooks.”

The results showed individual terminals from more than one retinal ganglion cell in a mature mouse brain.

HNRNPA2B1 is the first m6A nuclear reader to be identified, and evidence from the experiments suggests the existence of additional readers within the nucleus that also recognize this tag.

“The discovery of this new m6A reader has ramifications for a broad range of processes,” Alarcón says. “RNA splicing establishes the repertoire of proteins available in cells. Meanwhile, abnormalities in microRNAs have been associated with several diseases, including cancer.

“This work also contributes to growing evidence that information beyond the sequence of RNA, such as chemical modifications, can determine the ultimate fate and function of RNA molecules.”

Article adapted from a Virginia Tech news release by Ashley WennersHerron.

Publication: Multiple Retinal Axons Converge onto Relay Cells in the Adult Mouse Thalamus. Hammer, S et al. Cell Reports (August 27, 2015): Click here to view

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Source: Study Reveals Unexpected Details About Visual Connections in Brain, Overturning Textbooks

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