Neuroscientists map sensory gatekeepers in the brain with unprecedented detail

Reviewed by Emily Henderson, B.Sc.July 22, 2020

Many people with autism experience hypersensitivity, attention deficit, and sleep disorders. One brain region involved in these conditions is the reticular thalamus (TRN), which is thought to function as a gatekeeper for sensory information flowing into the cortex.

Researchers at MIT and at the Broad Institute at MIT and Harvard have now mapped TRNs with unprecedented detail. It was revealed that this region contains two different sub-networks of neurons with different functions. Guoping Feng, one of the research team’s leaders, said the findings could give researchers more specific targets for designing drugs that can relieve some of the autistic sensations, sleep, and attentional symptoms. It may be provided.

The idea is that you can very specifically target a particular group of neurons without affecting the whole brain or other cognitive functions. “

Guoping Feng, James W. and Patricia Poitras MIT Professor of Neuroscience, and a member of the McGovern Institute for Brain Research at MIT

Feng Shui; Zhanyan Fu, Associate Director of Neurobiology at the Stanley Center of Psychiatry Research Center at Broad Institute. Broad Institute’s Senior Group Leader, Joshua Levin, is the senior author of the study and was announced today. Nature.. The lead authors of this paper are former MIT postdoc Yinqing Li, former Broad Institute postdoc Violeta Lopez-Huerta, and Broad Institute researcher Xian Adiconis.

Different population

When sensory input from the eyes, ears, or other sensory organs reaches the brain, it first reaches the thalamus, which then relays it to the cortex for high-level processing. Disorders of these thalamocortical circuits can cause attention deficit, hypersensitivity to noise and other stimuli, and sleep problems.

One of the major pathways controlling the flow of information between the thalamus and cortex is TRN. It serves to block distracting sensory inputs. In 2016, Michael Halassa, assistant professor at Feng and MIT, Nature In the paper, we found that loss of a gene called Ptchd1 had a significant effect on TRN function. In boys, loss of this gene carried on the X chromosome can lead to attention deficit, hyperactivity, aggression, intellectual disability, and autism spectrum disorders.

In that study, the researchers found that when the Ptchd1 gene was knocked out in mice, animals displayed many of the same behavioral defects that were found in human patients. When knocked out with TRN alone, mice show only hyperactivity, attention deficit, and sleep disorders, suggesting that TRN is responsible for these symptoms.

In the new study, researchers hoped to find new ways to treat hyperactivity and attention deficit, and wanted to learn more about the specific types of neurons found in TRN. Currently, these conditions are most often treated with stimulants such as Ritalin, which affects the entire brain.

“Our goal was to find a specific way to regulate the function of thalamocortical output and associate it with neurodevelopmental disorders,” Feng said. “We decided to use single-cell technology to analyze which cell types are present and which genes are expressed. Are there specific genes that can be dragged as targets?”

To explore that possibility, researchers sequenced messenger RNA molecules found in TRN neurons and identified the genes expressed in those cells. This allowed us to identify hundreds of genes that could be used to differentiate cells into two subpopulations, based on how strongly they expressed a particular gene.

They found that one of these cell populations was located in the core of TRN and the other formed a very thin layer surrounding the core. These two populations also form connections to different parts of the thalamus, the researchers found. Based on these connections, researchers say that cells in the core are involved in relaying sensory information to the cortex of the brain, whereas cells in the outer layer are involved in different sensations such as vision and hearing. I’m assuming it will help adjust the information coming in.

“Draggable target”

Researchers are currently investigating the different roles these two neuronal populations play in different neurological conditions such as attention deficit, hypersensitivity, and sleep disorders. Using genetic and optogenetic techniques, they want to determine the effect of activating or inhibiting different TRN cell types or genes expressed in those cells.

“This will help us develop specific draggable targets that in the future may actually tweak various features,” Feng says. “Thalamocortical circuits control many things, such as sensory perception, sleep, attention, and cognition, but they may be more specifically targeted.”

Researchers say this approach may be therapeutic, even if the impairment of attention and hypersensitivity is not caused by a defect in TRN function.

“TRN is a target that could enhance its function to fix problems caused by impairment of thalamocortical circuits,” Feng said. “Of course, we’re far from developing all sorts of treatments, but we’re potentially using single-cell technology, not just to see how the brain itself is organized, We can also understand how the features are separated so we can identify more specific targets that tune a particular feature.”