Behind the Science: an Introduction to Connectomics

foleor. “The changing course of a river” Imgur. Web. 30 July. 2014. (Created using earthengine.google.org which uses Google satellite data from 1984 to 2012)

Scientists are always finding that things we thought would never change are actually in constant motion. Up until just a century ago, it was thought that the earth itself was unchanging. The connectome is no different. Neuroscientists have found that the connections between your neurons will change over time.

In the same way that someone can tell where the riverbed is just by looking at the river, neuroscientists can tell where there are connections based on how neurons fire together. One of the unseen processes of the river is how it changes the riverbed; over time, the flow of water will change the shape of the riverbed, which will eventually change the path of the river. Just as the river shapes the riverbed which guides it, neural activity shapes the connectivity in the brain, redefining your connectome.

c_elegans_connectome
The Connectome of C. elegans. Each dot represents a neuron, and each line a connection. Image: Mitya Chklovskii

A connectome is a wiring diagram of all the neurons in an animal. Your connectome consists of all the neurons in your body and the connections between them. Typically this is simplified to focus just on the brain.

The Four Rs of your changing connectome

Reweighting

A synapse’s size is an indicator of its strength. Synapses grow and shrink based on use; the more often a synapse is used, the larger it will become. Alternatively, if a synapse is unused for a long enough period of time, it may shrink and eventually disappear. The process of synapse growth and shrinkage is known as reweighting.

Neuroscientists attempt to model synapse reweighting using Hebb’s Rule. This rule describes how the firing of one cell will affect another one over time. Neuroscientists attempt to model synapse reweighting using Hebb’s Rule. By improving on this rule, the models of synapses will be a better representation of real synapses.

Reconnection

Rather than creating synapses at the specific locations that they are needed, neurons create synapses seemingly at random. As synapses get reweighted, synapses that shrink will be eliminated, while the others will be kept. This process, called neural darwinism, is thought to be responsible for transferring memories from short term to long term.

Rewiring

One of the leading theories in neuroscience is that the brain’s functionality is made possible by coordinated functional, genetic and connectomic relations between regions in the brain. To find the connections, neuroscientists map axons in the brain. Because the wiring of the brain plays an important role in defining its function, it is thought that in order to retain function in a damaged brain, the neurons will rewire.

Regeneration

The olfactory bulb and the hippocampus are the only two regions in the brain to create new neurons. It is unclear as to why neurons are only created in these two regions, but there are some theories that the stability of the brain is required for the continuing storage of old information. Scientists hope to replicate the process of neuron regeneration for other parts of the brain to help treat brain damage.

I am my connectome

The picture at the top of the page is called “The C. elegans Connectome.” By calling it the connectome, it is implied that all C. elegans roundworms have identical connectomes, or that they are connectome twins. While no two C. elegans connectomes have been fully mapped, researchers have found by comparing the connections in the tail ends of the roundworm that there are differences between individuals. Therefore, “A C. elegans Connectome” may be a more appropriate name.

Even though the connectome of a C. elegans roundworm is known, there are no fully accurate simulations of its behavior. C. elegans possesses a diverse group of neurons, and many of their functions are unknown. Because each type of neuron requires a model of its function, and the number of neuron types is similar to the number of neurons in C. elegans, the information in the models of neurons may exceed the information in its connectome. The specific balance of information in C. elegans has lead scientists to conclude that its connectome needs to be combined with much more information about the neurons for a simulation of its behavior.

By Kbradnam at en.wikipedia(Original text : Zeynep F. Altun, Editor of www.wormatlas.org) [CC-BY-SA-2.5 (http://creativecommons.org/licenses/by-sa/2.5)], from Wikimedia Commons
Although the roundworm’s connectome is insufficient for a description of its behavior, scientists believe a human’s connectome could be useful to understand human behavior. Humans have many more neurons than neuron types, so the connectivity in the brain is probably responsible for behavior, rather than the neuron types themselves. Sebastian Seung took a rather logical step forward from this theory, claiming that our self identity and consciousness arise from our connectomes, in his statement “I am my connectome.”

Using the connectome to understand the brain

By studying the differences in people’s connectomes, neuroscientists hope to be able to show how mental disorders are caused by specific connectopathies, disorders of neural connectivity. These connectopathies could help diagnose and treat mental disorders such as PTSD, schizophrenia or autism.

It could also one day be possible to better understand human cognitive strengths, such as learning and problem solving.

Connectomics and EyeWire

EyeWire is both helping to develop the tools to find connectomes and mapping parts of a mouse’s retinal connectome to advance our current understanding of vision.

Because EyeWire is the first game of its kind, the tools used, such as the Artificial Intelligence (AI), are paving the way for future connectomics projects to be created and become successful. Neuroscientists hope that the AI, which allows semi-automated analysis of neuroimage data, will one day surpass the abilities of humans for mapping the connectome and significantly speed up the process of finding connectomes.

The cells mapped in EyeWire are also used to  improve our understanding of basic visual processing in the retina.

This May, an article from EyeWirers and Seung Lab, has been published in the journal Nature, titled “Space-time wiring specificity supports directional selectivity in the retina.” EyeWire players helped discover a solution to a longstanding mystery of how a mammal is able to tell in which direction something it sees moves.

starburst, bipolar cell, eyewire, neurons, Nature, citizen science, neuroscience, brain, commectome, mIT
Starburst neuron (red) and bipolar cells (green,blue). Image: Alex Norton

You can watch Sebastian Seung’s TED talk about Connectomics here! Keep an eye on the blog for the next installment of Behind the Science.

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