May 13, 2008

Three-Dimensional Thinking

A lot of the work I’ve been doing in lab lately is related to brain development. Your brain is an absolutely amazing mess of pathways, fibers and tracts. The interconnected nature of the brain is far more sophisticated than simple dendrite trees in a big cluster. Furthermore, your brain and my brain are nearly identical, as far as gross anatomy is concerned. You have a hypothalamus, an amygdala, a corpus callosum and a suprachiasmatic nucleus, etc etc ad nauseum. The connections between the various brain regions is likewise similar. This simple fact is actually quite astonishing: every human brain is hardwired to organize into the same gross pattern.

Indeed, hordes of researchers are actively pursuing the mysteries of brain development. Many diseases are caused by improper maturation of the brain. It is becoming increasingly clear that the development of the brain, while complicated, is by no means magic. Various signaling chemicals and peptides direct axons to their destination, either attracting or repelling. Chemical gradients create complex migration behavior depending on your location in the gradient. Importantly, this intricate chemical dance is entirely reproducible - it is the reason your brain looks like mine.

The previous iteration of Distributed Neuron consisted of essentially random placement and a semi-random connection system (through the use of simple “chemical” attractants). This system left a lot to be desired. Results were unpredictable each iteration due to the inherent random nature. Gross anatomy was difficult to develop because neuron placement was random and fixed. Once a neuron was placed, it was permanent. The connection system allowed minor segregation by influencing the direction and distance neurites could travel. It was, in my opinion, too little of an affect to be worthwhile.

Enter the newest revision. Again, neurons are placed into a three-dimensional environment. Each neuron is a 1×1x1 cube. Initial placement is fixed and predictable. This iteration, instead of immediately growing neurites for connections, enters a “migration” phase. Each neuron has a base migration value that defines how far and in what direction it travels. Chemo-emitters are strewn about the three-dimensional space. As neurons migrate, they may change their differentiation pattern according to what chemo-emitters are nearby. This differentiation change affects the base migration properties, altering migration direction. Importantly, no randomness is involved so the results are identical each time.

In this way, neurons not only migrate to different positions but also change their cell fate depending on their location. The non-random nature makes testing/analysis easy because the results are identical from one run to the next. Small variations in the placement and quantity of chemo-emitters can drastically alter the gross anatomy of the network, providing an infinite supply of variations.

There are still pieces I would like to iron out, but for now, the system works very well and can produce some interesting results. Here is one such sample network, from two different views. It consists of 10,000 neurons and has already performed its “migration” phase.

Colors indicate different cell “types”. This particular network has 4 cell types (red, magenta, blue, and one lonely green). As you can see, the network formed a thick magenta sheet. Pressed against this are two separate sheets, one blue and one red. It should be noted that the initial placement of neurons was actually in the bottom-right corner of the screen, meaning the neurons migrated top-left. It should also be known that initial placement was in a small cube, which proceeded to flatten and elongate into a sheet.

Click for big.

10,000 Neurons, alternate view 10,000 Neurons

Leave a Reply