Build a whole brain map: I am not fish, also know the joy of fish and sorrow.

During the Spring and Autumn Warring States period, two thinkers, Zhuang zi and Huizi, had an interesting dialogue.
Hui two people go out to play, cross the river when they see the bridge under the riverfish.
then Zhuangzi sighed: " fish in the water leisurely, this is the joy of the fish ah ( fish travel calmly, is the fish music also).
" Huizi disagreed, asked: "You are not the fish himself, how do you know the joy of the fish (sub-fish, Anzhi fish joy)?" "More than 2000 years later, Huizi's problem is still a problem.
, until we have an objective understanding of the correspondence between fish behavior (specific swimming actions) and brain activity (inner pleasure or not), this question can only be answered on the basis of subjective assumptions.
is it possible for us to know if fish are happy? In 2013, a team of researchers at the Howard Hughes Medical Institute in the United States reported a major breakthrough: They fixed fluorescently modified young zebrafish all over the body and successfully tracked the real-time neuron dynamics of zebrafish through laser flacography microscopy.
, however, which neurons produced signals in the experiment were? Why do fish are so active in some brain areas when they are fixed, while others are almost static? Without an all-brain map, the authors of the paper were unable to further infer the function of the various parts of the fish's brain and their relationship to behavior.
want to truly understand the brain in a complete way, or need to build an entire brain map.
first seriously tried it was Santiago Ramon-Kahar, known as the "father of neuroscience."
beginning in 1887, Kahal used the state-of-the-art Gorky dye method to stain brain samples of various animals, including human corpses, and place them under a microscope for observation, and to remove neurons one by one.
Kahal's paintings had a huge impact on neuroscience (Kahar won the Nobel Prize in Physiology and Medicine in 1906).
earlier this year, the paintings even starred in the Art Exhibition "Beautiful Brains" in New York.
, however, one neuron is still a long way from building an "whole-brain map."
brain is made up of a large number of neurons.
these networks of neurons, which are linked together, form the biological basis of animal behavior.
to build an "whole brain map" that requires an experimental technique that locates the position of each neuron at the same time and distinguishes the details of the two neurons' connections (synapses).
the connection between many neurons and neurons is less than 10 nanometers, while the resolution of a common optical microscope cannot be reduced below 200 nanometers by the optical diffraction limit.
rapidly developing ultra-resolution fluorescence microscopy in recent years, while reducing this limit to 10 nanometers, cannot simultaneously sample all regions of the brain.
electron microscope technology is a microscope technique that displays the interior or surface of an object by electrons.
the resolution of the microscope is generally limited by the wavelength of the particles it uses (for example, the resolution of the optical microscope is limited by the wavelength of light), the electron wavelength of high-speed motion is much longer than the visible light wave, so the resolution of the electron microscope is much better than that of the optical microscope, and a more subtle structure can be seen.
, at present, only electron microscopy can meet the requirements for building a "full-brain map": it has a resolution of 0.2 nanometers and is able to sample all regions of the brain at the same time at that resolution.
recently, the Davi Bock team at the Howard Hughes Medical Institute in the United States announced that they had used transmission electron microscopy to analyze the entire brain map of a female fruit fly.
traditional electron microscopy techniques have strict limits on the size of a sample - the sample can not be more than 100 nanometers thick, while most biobrain tissues are more than 100 nanometers thick.
female fruit fly has a brain size of about 750 microns x 350 microns (750,000 nanometers x 350,000 nanometers).
they developed a new transmission electron microscope platform by improving traditional electron microscopes, successfully cutting the female fruit fly's brain into 7,050 pieces and taking pictures of each section of each slice, collecting a total of 21 million photos (106TB).
the team selected a brain region (mushroom body) in the fruit fly's brain associated with learning and memory behavior for tracking markers (because the front and back of the same neuron may appear in photos of different brain slices), and found a new group of neurons in that brain region.
other brain regions in the fruit fly's brain are now being tracked separately by teams of experiments around the world.
if you're interested, you can also participate in the work of neuronal markers in the fruit fly's brain by downloading raw data.
Bock's team reported that the fruit fly's whole brain map is the latest attempt by neuroscientists to map the fruit fly's whole brain.
as early as the end of 2016, a multinational team of researchers from Professor Jiang Anshi of Taiwan, Daniel Coca of the University of Sheffield in the United Kingdom and the Aurel Lazar research team at Columbia University in the United States published a full-brain map of fruit flies collected through optical microscopes (the resolution is lower than the whole brain map of the Bock research team).
all of its image data can be found at the Fruit Fly Brain Observatory.
as the most common pattern of organisms, fruit flies have made great contributions to our understanding of genetics and neuroscience.
more than 100 years ago, Morgan discovered the laws of chain and interchange between companion genetic laws and one of the three famous genetic laws by studying fruit flies, and won the 1933 Nobel Prize.
last year, three scientists studying biological rhythm behavior won the Nobel Prize for Physiology and Medicine, and fruit flies were the best assists.
The Bock team's research marks both our ability to build a full-brain map of fruit flies and a difficult and important step in our understanding of the brain and ourselves.
starting with the fruit fly's brain map, analyzing the entire brain map of more creatures, including fish, may gradually become a reality.
by then, on the question of Huizi, we may be able to bring up the fish's full brain map and related behavioral data, answer: I am not fish, also know the joy of fish.
(The author is a Ph.D. student at the University of California, San Diego)