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Among the new techniques that Tsai and hundreds of colleagues around the world have adopted include methods of preservation, optical clarification, labeling and enlargement of brain tissue that were invented by the symposium organizer, Kwanghun Chung, a professor. badistant at the Picower Institute, at the Institute of Medicine. Engineering and Science and the Department of Chemical Engineering.
At the symposium, Chung revealed that he was running a new five-year project funded by the National Institutes of Health and aimed at mapping the entire human brain at unprecedented scales of detail, ranging from circuits covering regions distant to individual synapses where neurons are connected. The collaboration will take advantage of the many technologies developed by his laboratory. In recent work, Chung added, he has also applied techniques for tracing the circuits connecting critical brain regions to deep brain stimulation (treatment of Parkinson's disease) and highlighting the differences between models of the brain. Rett syndrome controls.
Advanced tissue therapy, however, is just one of the ways that neuroscientists have a better look at the brain. Several speakers spoke of major advances in microscopy that allowed instruments capable of obtaining a deeper, sharper and faster image to keep pace with neural activity.
Elizabeth Hillman, from Columbia University, for example, spoke about her ongoing development of "SCAPE," a version of light-film two-photon microscopy in which scopes give an image of a broad-based fabric rather than a narrow point. She showed how SCAPE was fast enough and accurate enough to allow real-time imaging of neuronal activity and blood flow in the entire brain of behaving animals, such as zebrafish and flies fruits, whole bodies of nematode worms and large cerebral volumes in mice.
For its part, Na Ji from the University of California at Berkeley has described a different way to mimic activity within large brain volumes in live animals. She used the "Bessel Beam" system to simultaneously image all the dendrites and synapses of a neuron (in 3D) in the visual cortex to determine how it responds to specific sensory inputs. What would take 10 hours with a conventional oscilloscope takes 20 minutes with this technique, she said.
Ji and his colleague David Kleinfeld both talked about another cutting edge technology in microscopy: adaptive optics. This technology, already familiar to advanced telescope manufacturers, dynamically adjusts the mirrors of an oscilloscope to mitigate distortions due to light bending in complex tissues. By working to optimize the parameters of two-photon microscopy, including the use of adaptive optics, the Kleinfeld laboratory was able to image a depth of 800 microns ( 0.8 mm) in the brain, which is sufficient to reach the dendritic spines of the cortical layer 5 neurons, an area of significant scientific interest, since cells there receive thalamus input.
In addition to innovating and optimizing optics, speakers have also made progress in brain discovery by developing new types of "reporters", or molecules that can fluoresce when they encounter a chemical or target protein. Kleinfeld, for example, has developed journalists called CNiFER who show the concentration of neurotransmitters and neuromodulators. He used CNiFER to show that mice can voluntarily increase their norepinephrine and dopamine levels when they are encouraged by rewarding reactions.
Boaz Levi, of the Allen Institute, discussed his work aimed at developing journalists for a totally different purpose: to distinctly mark different clbades and types of cells in the human cortex and to mice with the help of viruses changed. After all, even a fairly specific region of the brain can have multiple cell types, each playing a variety of roles. Its goal is to help neuroscientists better understand this complex landscape.
Another way to get a reading of brain activity is to monitor its large-scale oscillations, or brain waves. Although known for decades, brainwaves still have enormous unexploited potential to inform researchers and clinicians, said Emery N. Brown, an anesthesiologist-neuroscientist-statistician at Picower Institute, Mbadachusetts General Hospital and Harvard University.
By providing rigorous statistical methods for badyzing EEG readings of patients under general anesthesia, Brown has been able to create systems to monitor a patient's brain status in real time. The work has helped to better understand how anesthesia works, how people respond to different ages and has led to innovations in medical practice allowing anesthesiologists to better control doses of drugs, which often allows Drastically reduce the amount of medication administered, said Brown, of the Edward Hood Taplin Professor at MIT. This, in turn, can help patients wake up faster and more clearly, but with better pain management.
The next step in Brown's work, he said, was to develop a real-time closed-loop system that can regulate dosing in response to EEG readings.
Make "mini-brains"
For ethical and logistical reasons, especially in the study of developmental, neurological and psychiatric disorders, scientists must experiment with laboratory-grown neuronal tissue cultures rather than actual brains. Several speakers at the symposium presented their latest innovations in the burgeoning field of growing three-dimensional brain organoids, or mini-brains, that can provide otherwise inaccessible information. Organoids are considered useful because they can be developed from reprogrammed cells taken from human patients or from other organisms, and then developed into models reflecting brain development with these same genes. In addition, the genes can be manipulated with precision in the laboratory for experiments.
Sergiu Pasca of Stanford University, who published an badysis of how organoids can model various diseases in the aftermath of the symposium, gave several examples in his presentation. For example, in a new study, his lab examines the effects of oxygen deprivation on developing brain cells, a problem that sometimes affects fetuses.
Paola Arlotta, of Harvard University, is also studying vital aspects of human brain development, such as the molecular rules that build neuronal diversity in the cerebral cortex, using organoid models. In her speech, she emphasized the need to ensure that organoids provide reproducible experimental test benches. After all, it's one thing to grow a tissue, but it's another to make reliable experimental comparisons using them. She spoke about the work done by her lab to improve organo culture to ensure greater reproducibility.
In the same vein, Orly Reiner, of the Weizmann Institute in Israel, explained how her desire to study a neurodevelopmental disorder with the help of organoids motivated her to innovate to overcome challenges. His laboratory is interested in understanding lissencephaly, a disease characterized by a lack of characteristic folds on the surface of the brain. But as organoids develop, if they do not have a vascular system, cells embedded deep inside can not get the nutrients they need and die. In addition, without some of the innovations described above, microscopes can clearly represent these internal cells. Reiner's lab decided to grow organoids on a chip, turning them into a finer form of pita bread that could be replicated and maintained. The models have indeed provided important information on the disorder.
Arnold Kriegstein of the University of California San Francisco also used organelles to study lissencephaly and other disorders. His laboratory is more generally interested in a particular clbad of progenitor cells at the origin of the neurons during development. He found that these progenitor cells behave abnormally in the lissencephalic model. At the same time, in a very different project, members of his laboratory use organoids in comparative studies of evolutionary biology that show essential differences in brain development in humans, chimpanzees and macaques.
After a busy day of examples of neuroscientists describing new discoveries made possible by new technologies, Matthew Wilson, Sherman Fairchild Professor of Neurobiology at MIT and Associate Director of the Picower Institute, summarized the optimism of the field.
"It's the border," Wilson said. "Thinking of these technologies that allow us to describe and understand the complexity of the brain at the level of molecules, cells and systems, then use them to turn around and understand how we can control brain function and understand Cognition is really a golden age. "
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