Mapping the Brain

Introduction

Despite the extensive research conducted by thousands of neurobiologists, our understanding of how brains work remains limited. The brain is one of the most intricate and fascinating objects known in the universe, and unraveling its mysteries holds immense excitement for scientists. At its core, our goal is to comprehend how this small organ generates everything we experience.

The term "connectomics," which we coined by chance, draws inspiration from "genomics," the mapping of all genes. We proposed the idea of creating a comprehensive map of the connections between nerve cells. While understanding the brain is fundamentally a biological challenge, acquiring a large-scale map involves the intersection of imaging, computer science, and software development. The human brain, when examined at microscopic levels, is surprisingly complex, potentially generating an overwhelming amount of data—up to an exabyte, equivalent to a million terabytes. This magnitude of information poses challenges; mapping the entire human brain could require billions of dollars and decades of work. Thus, researchers recognize the necessity of beginning with simpler organisms that can be studied and understood more feasibly within a shorter time frame.

The first successful connectome mapping was conducted on the transparent roundworm known as C. elegans, which has just 302 neurons. The painstaking process included taking high-resolution images of the worm's slices using electron microscopes and manually tracing the neuronal connections on large micrographs. This intricate task took a decade and discouraged further exploration of other connectomes for nearly 20 years. It wasn’t until the 2000s, with significant technological advancements, that researchers sought to undertake more complex mappings.

Recent efforts focused on the fruit fly brain, which has around 100,000 neurons and demonstrated interesting behaviors related to learning and memory. The mapping of the fly brain generated massive datasets, encompassing numerous computational processes necessary to extract practical knowledge from the raw images. Google Research's collaboration was crucial in processing these vast amounts of data, which would have otherwise required millions of hours of human effort to analyze.

One of the major challenges in this endeavor was the segmentation or tracing problem, wherein researchers needed to identify and map each neuron within a three-dimensional dataset. They developed a 3D convolutional network approach tailored to improve automated neuron tracing. Additionally, visualization software named Neuroglancer was created, enabling researchers to view and analyze the datasets and their 3D reconstructions conveniently through web browsers.

Findings from mapping the fruit fly's brain revealed a strong relationship between neuronal structure and function. The morphology of neurons and their connections provided essential insights into the brain’s activities, offering clues to the purpose of different neurons—insights that were not evident before starting this research.

As researchers look ahead, the logical next target for connectomics is the whole mouse brain, which is approximately a thousand times larger than a fruit fly brain yet remains a thousand times smaller than a human brain. Electron microscope images show that the mouse brain resembles a miniature version of the human brain. While mapping an entire mouse brain presents its challenges, the knowledge gained could be significant enough to eliminate the need for mapping the human brain entirely. Ultimately, it may lead to a deeper understanding of memory formation, recognition of mental disorders, and other critical areas in neuroscience—a vision that would have been unimaginable to earlier generations.

Keywords

• Connectomics
• Neurons
• C. elegans
• Fruit fly brain
• 3D convolutional network
• Neuroglancer
• Mouse brain
• Memory formation
• Mental disorders

FAQ

Q: What is connectomics?
A: Connectomics is the study of mapping the connections between nerve cells in the brain, akin to how genomics maps all genes.

Q: Why is understanding the brain a significant challenge?
A: The brain is incredibly complex, and acquiring a comprehensive map requires vast amounts of data, advanced imaging technology, and extensive computational resources.

Q: What are some organisms that have been mapped in connectomics research?
A: The first connectome was mapped in the worm C. elegans, followed by efforts to map the fruit fly brain, which has around 100,000 neurons.

Q: How did technology aid in mapping the fruit fly brain?
A: Collaboration with Google Research provided the necessary computational power and expertise to process large datasets efficiently.

Q: What is the next target for connectomics research?
A: The next target is mapping the entire mouse brain, which is expected to yield significant insights into brain function and information storage.