Connectomics is the area of neuroscience that aims to collect and curate the entirety of the connections made by all neurons in a brain (the product being called a “connectome”). For the human brain, that would be a data set of 100 billion neurons, each of which is estimated to make 1000-10000 synapses with other neurons (on the order of 1017 connections). The roll-up-your-sleeves-this-will-get-really-messy way of collecting that kind of data is to slice the brain into nanometers-thick sections and to image each slice with an electron-microscope, which has resolution below the nanometer range, and can reveal the structure of cells on a fine scale. In the image from Kristen Harris's lab below you can see a part of a neuron’s dendrite making a synapse with an axon filled with neurotransmitter vesicles; EM images however cannot show individual proteins or molecules).
Whale Song Analysis Crowd-sourcing
Scientific American is collaborating with marine scientists on a project to crowd-source analysis of whale songs and calls. Having gathered thousands of sound files from many species of whales, scientists now need to classify each call and song to get an understanding of each specie's repertoire. Once the calls and songs are sorted and classified, scientists can pursue interesting questions like, is a whale's song repertoire related to its intelligence? To classify the vocalizations, scientists are asking the public for help. On whale.fm, anyone (no expertise required) can sift through some spectrograms and embedded sound files, and match them to a template. It's easy, fun and cool. Something that would take one person months or years to do, can now by accomplished much faster by the public in a fun format.
Some previous efforts in scientific crowd-sourcing like FoldIt, a game in which people fold proteins based on simple rules (computers can't do this), or the search for new galaxies by amateur astronomers from images taken by the Hubble telescope. Perhaps this type of effort could help the Connectome efforts to map out the brain down to each synapse using electron microscopy, where every neurite in a cross-sectional image must be strung to itself in adjacent images. Tracing axons across thousands of EM images could actually make a fun and productive game.
Here is a nice interview with Jeff Lichtman of Harvard, who is working on a cellular-level map of synaptic connections in the brain (a connectome). The interview raises several questions, like how can we collect thousands of petabytes (millions of gigabytes) of data of the structure of the brain at the level of individual cells? Do we even need so much data? Even though connectomics won't reveal much about neural dynamics (i.e. how neurons actually transmit or integrate information), it should be a useful tool for further work in theoretical neuroscience. Someone has to do it. One caller in this interview asks a great question on the hard problem of consciousness: when scientists look at neuronal activity when one is thinking of a childhood pet, where in the universe is that image of the dog? All the scientists see, after all, is electrical activity...
Connectomics is the name. Connections are the game.
You are unique, just like everyone else. Connectomics is the study of the structural and functional connections among brain cells; its product is the "connectome," a detailed map of those connections. The idea is that such information will be monumental in our understanding of the healthy and diseased brain. Sebastian Seung thinks that a complete connectome of the human brain will be one of the great prizes in 21st-century neuroscience.
Efforts to construct brain connectomes are split into two categories: ones that use imaging techniques like MRI, PET, and DT, thus focusing on macroscopic connections or tracts; and those that use electron microscopy to map the tinniest of axons (0.2-20 microns in diameter) and individual synapses.
While this may sound daunting, it also seems the obvious thing to do in order to really understand how the brain works. After all, don’t all our memories, personalities, and behaviors dependent on the structure of the brain, down to the microscopic level? So why is connectomics so new? Because the three-pound enigma that can contemplate all things big and small – from protons and electrons, to planets and stars, to galaxies and the whole universe – contains more parts than anything we’ve ever studied before. The human brain, we’ve been told, holds 100 billion neurons, with close to one quadrillion synaptic connections total; storing all of that information in one brain would take one Exabyte of data (that’s one trillion Gigabytes).
Jeff Lichtman and colleages at Harvard remain hopeful. They are developing novel tools to automate the tedious task of scanning brain slices. They expect the connectome to reveal differences in the way healthy and diseased brains are wired.
The effort is laudable, considering its scope and ambition, but it begs the question: does all behavior, experience, perception, etc depend on the structure of synapses and connectivity of neurons? More pointedly, does structure determine all function – chemical and electrical? Sure, larger synapses or more dendritic spines make stronger connections and more efficient transmission of information, but a snap-shot connectome won’t take into account temporal dynamics and enzymatic processes, which play a big role in the active brain.
In his TED talk, Sebastian Seung says that to test the hypothesis that “I am my connectome,” we could try to read out memories from someone’s connectome. But memories are not just synaptic connections – they are also assemblies of neurons in time or firing sequence. The connectome does not take those into account. And Seung fails to explain how we could actually verify any of those personal memories, since current methods of constructing a connectome involve cutting the brain into thousands of 30-micron slices.
If we could devise some non-invasive methods to construct a human connectome at the synapse level, what ethical issues would we face? Could a personal connectome be the ultimate breach of privacy? Could it redefine or “undefine” what we consider to be normal brains/mental states?
Constructing a comprehensive human connectome is a great challenge. A bigger challenge would be to model the electrical dynamics of the 100 billion human neurons. But perhaps the most important quest for neuroscience isn’t building a connectome, but learning how neuronal activity creates experience.
Neurocartography - Narayanan Kasthuri and Jeff Lichtman via NIH Public Access
Sebastian Seung: I am my connectome - TED.com
Seeking the Connectome, a Mental Map, Slice by Slice - NYTimes.com