The brain plays an essential role in how people navigate the world by generating both thought and behavior. Despite being one of the most important organs of life, it takes up only 2% of the volume of the human body. How can someone so small do such a complex task?
Fortunately, modern tools like brain mapping have allowed neuroscientists like me to answer this exact question. By mapping how all types of cells in the brain are organized and examining how they communicate with each other, neuroscientists can better understand how the brain normally works, and whether Occurs when certain cell parts are missing or damaged.
history of brain mapping
The task of understanding the inner workings of the brain has fascinated both philosophers and scientists for centuries. Aristotle proposed that the mind is where the soul resides. Leonardo da Vinci made creative depictions of the brain with wax embeddings. and Santiago Ramón y Cajal, with his 1906 Nobel Prize-winning work on the cellular structure of the nervous system, made one of the first breakthroughs that gave rise to modern neuroscience as we know it.
Using a new method to visualize individual cells called Golgi staining, a method pioneered by Nobel co-winner Camilo Golgi, and microscopic examination of brain tissue, Cajal established the seminal neuron theory. This theory states that neurons, one of the main types of brain cells, communicate with each other through gaps between them called synapses. These findings started the race to understand the cellular structure of the brain and how brain cells are connected to each other.
Since then neuroscience has experienced a rapid explosion of new experimental tools. Moving forward 100 years from today, modern tools called Neurotechnics, which include brain mapping, have given neuroscientists a way to closely observe every component of the brain. My lab is using these brain mapping tools to understand what types of cells make up the brain and how they contribute to the formation of cognition.
the science of brain mapping
So how does brain mapping work?
Scientists first need to label or visualize a specific cell type. The process is like finding a needle in a haystack – it will be much easier to find out if the needle, or cell type, shines. This can be done with either genetic or immunostaining methods. The genetic method takes advantage of animals, like mice, which can be genetically engineered so only the target cell type is visible under specific fluorescent lights. Immunostaining methods, on the other hand, make brain samples transparent with a specific chemical treatment and use antibodies to label the target cell type with a fluorescent tag.
The next step is to image the whole brain using microscopy techniques that allow scientists to see parts too small for the naked eye to see. Specialized microscopy equipment can take a snapshot or tile of the entire brain. Stitching these image tiles together allows an intact 3D volume to be reconstructed, like a photo mosaic. It’s like creating a Google Map of the brain: Combining millions of different street photos, you can zoom in to see each street corner and zoom out to see the entire city.
Unsurprisingly, this type of 3D imaging produces very large datasets. Even though mouse brains are smaller than human fingers, the size of these datasets can easily reach anywhere from a few hundred gigabytes to terabytes. Fortunately, remarkable advances in computer equipment and software have made large-scale data analysis possible. Artificial intelligence algorithms in particular have enabled scientists to detect many different cell characteristics in the brain, such as cell shape and size, as well as the processes they undergo.
Once scientists are able to locate their target cell type in an image dataset, the final step is to locate specific cell features in a reference brain. This reference brain serves as a standardized map showing where each brain region is located. Scientists can then use this map to compare different brains and note their variations.
These steps are repeated for each cell type, with each run-through producing a richer and more complete map of the brain.
working together to create a brain map
Scientists now have the tools to examine the whole brain very closely. Considerable effort has been made to coordinate and pool the data from the Brain Mapping Research Lab to produce a comprehensive brain map. For example, the US Brain Initiative created the Brain Initiative Cell Census Network (BICCN) in which my lab participates. Research groups collaborating in the network recently released the most comprehensive map of cell types in the motor cortex of the brain in humans, monkeys and rats.
But is this enough to understand how the mind works?
Technological advances in cell staining and microscopy helped Santiago Ramón y Cajal make his important discoveries about neurons. However, it was his ability to come up with a theory to explain his observations that advanced neuroscientists developed an understanding of the brain.
While researchers have been busy collecting incredibly detailed information about the brain, using this data to form new theories about how the brain works. A map of cells does not necessarily tell researchers how cells function and interact with each other as a whole. For example, how do these incredibly complex networks of brain cell types work together to produce cognition? Is there a basic unit in the brain that dictates how it is formed and functions? Answering such questions will help researchers better understand how specific brain changes are associated with various brain disorders such as dementia and come up with new strategies to treat them.
This is a very exciting time for neuroscience research. The incredibly rich, high-resolution brain mapping presents a great opportunity for neuroscientists to take an in-depth look at what this new data says about how the brain works. While there are still many unknowns about the brain, these new tools and techniques may help bring them to light.
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