Otx2 helps a key type of cell in the cortex to mature, initiating a critical period -- a window of heightened brain plasticity, when the brain can readily make new connections.
The work was done in a mouse model of the visual system, a classic model for understanding how the brain sets up its wiring in response to input from the outside world. But Takao Hensch, PhD, of the Neurobiology Program and Department of Neurology at Children’s, the study’s senior investigator, speculates that there may be similar factors from the auditory, olfactory and other sensory systems that help time critical periods. Timing is important, because the brain needs to rewire itself at the right moment -- when it's getting the optimal sensory input.
“If the timing is off, the brain won't set up its circuits properly,” Hensch says.
Being able to control the timing of critical periods in different parts of the brain could possibly ameliorate developmental disorders such as autism, in which researchers believe critical periods may be inappropriately accelerated or delayed. Retriggering a critical period might also help people learn more readily after childhood – acquiring a new language, developing musical abilities or recovering from stroke or brain injury, for example.
Interestingly, Hensch and colleagues found that the brain cells that switch on critical periods in the visual system (parvalbumin cells) don’t actually make Otx2 themselves. Instead, Otx2 is sent by the retina. In essence, the eye is telling the brain, "The eyes are ready and seeing properly -- you can rewire now."
"The eye is telling the brain when to become plastic, rather than the brain developing on its own clock," says Hensch, who is also a professor at Harvard Medical School and at Harvard University’s Department of Molecular & Cellular Biology. “The idea that this class of molecular messenger is passed from cell to cell is considered unorthodox in cell biology.” This idea, however, has long been advocated by Dr. Alain Prochiantz of the Ecole Normale Superieure (Paris) and College de France, Hensch’s collaborator and a coauthor on the study.
It was previously known that when parvalbumin cells mature, they set up inhibitory circuits in the cortex, balancing the existing excitatory circuits. Hensch and others have shown that setting up inhibitory circuits is key in launching critical periods. “Early excitatory input is important to make first contacts between neurons,” Hensch explains. “But then, at the next stage, you need inhibition.”
In the current study, Hensch and colleagues demonstrated that when mice are reared in the dark, thus getting no visual input, Otx2 remains in the retina. Only when the mice received full visual input did Otx2 begin to appear in the cortex, and only then did parvalbumin cells start to mature.
In other experiments, the researchers injected Otx2 directly into the cortex. The parvalbumin cells matured, even when the mice were kept in the dark. Finally, when Otx2 synthesis was blocked in the eye, parvalbumin cell functions failed to mature.
Otx2 has an unusual derivation: it is originally produced during embryonic development; without it, mice don't develop heads. Production then stops, but some days after birth, it reappears in parvalbumin cells. “The nervous system is recycling an embryonic factor to induce brain plasticity,” says Hensch.
Hensch, who last fall won the highly competitive NIH Director’s Pioneer Award, is also interested in the transport mechanism that propagates Otx2 from the retina to the cortex. He speculates that Otx2 itself could be a carrier for factors you’d want to deliver to the brain, envisioning eye drops for brain disorders such as schizophrenia, in which parvalbumin cells don't properly mature.
The study was funded by the Human Frontiers Science Program (Strasbourg), the Fondation pour La Recherche Medicale, and in part by RIKEN (Japan) and the Japanese Ministry of Science, Education and Technology (MEXT). Sayaka Sugiyama, PhD, was first author.
Children’s Hospital Boston is home to the world’s largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 12 members of the Howard Hughes Medical Institute comprise Children’s research community. Founded as a 20-bed hospital for children, Children’s Hospital Boston today is a 397-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children’s also is the primary pediatric teaching affiliate of Harvard Medical School.
James Newton | Newswise Science News
The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung
A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences