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Full Version: Connectomics - Study of Neuronal Connections in Brain and Nervous System
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Brain is the central organ in the nervous system of all animals except few invertebrates. Everything we do is under brain's control and that’s the reason why scientists are so eager to "decode" it.

Brain is extremely complex organ, anatomically divided in multiple functional units (visual cortex, olfactory cortex…). Signals coming from the brain are transported via synapses. Although much information about brain is already known, there are still a lot of gaps that need to be filled. Number of neurons in the brain is enormous; just in cortex, there are between 15 and 33 billion neurons. Each one of them is connected with at least one other neuron, resulting in huge number of created synapses. Discipline focused on the research in the area of neuronal connections is called connectomics. Map of all synapses in the brain is called connectome (just like genome is set of all genes that one organism possesses). Tricky thing about connectome is that brain is dynamic system that is undergoing changes all the time. Network between neurons that were present while we were young will inevitably be altered as we are growing old. Learning is process that creates novel connections between neurons, and on the other hand, neurons have limited lifespan and once they die, link with the neighboring cells will be lost. However, the biggest problem in connectome project is asscoiated with tracking and counting the large number of existing neuronal cells and their connections. Fully explored and mapped brain belongs to C. elegans. It’s relatively simple connectome consisting of 302 neurons and 7000 connections. Mouse brain (>10^8 neurons) is under investigation, but there are still some technical issues that need to be solved before complete and accurate map of mouse brain become available.

Brain networks could be obtained in the couple of ways. Connections between cells could be determined on the cellular level by tracking each neuron and its connections. This approach is the hardest and complete mapping would demand substantial amount of time considering that over billion neurons are normally present in the brain of the highly evolved animals (just human cortex consists of 10^10 neurons creating ~10^14 synapses). Mapping connectome on this level is called microscale connectome.

Mesoscale connectome is focused on revealing anatomical and functional connection between larger populations of neurons (hundreds and thousands of cells sharing the same function).

Macroscale connectome is dealing with larger brain systems that are divided in functional nodes. Main goal is to determine their connectivity.

Several techniques are applied in brain mapping. Tracing agents and different staining techniques are used for single cell tracking; visualization of the neuronal networks is achieved by light or electron microscope. Disadvantage: these methods can’t provide long-range neural projection and light microscope derived images have low resolution. Improvements in the field of mapping individual neurons are made after applying fluorescent proteins in the process named brainbow. Method is relatively simple. Red, green and blue derivatives of green fluorescent protein are inserted and randomly expressed in the neuronal DNA, resulting in over 100 color variations that could be tracked using confocal microscopy. Brainbow is tested in mice, and so far, this method proved to be successful, especially for mapping complicated neuronal circuits. To obtain complete view of neural networks in the brain – thousands of pictures had to be collected and aligned to match perfectly. Method used in brainbow tracking inspired another group of scientist to develop new technique for neuron labeling. Using DNA sequences that are acting like a barcodes, each neuron could be marked. Connections between neurons could be established using viral vectors that will transfer another barcode to the following postsynaptic neuron. At the end, each neuron will be a “bag full of barcodes” (bearing his and virally transferred DNA sequences), grouped in pairs. High-troughput sequencing could further provide information on the neuronal connectivity. Sequencing is not as expensive as it was couple years ago, and this approach has a great chance to be successfully implemented in the future connectomics projects.

Although, all currently used methods have some weak points, they are constantly improving and mapping of the mammalian connectome will probably happen soon. Due to dynamic structure of the brain - every map will be unique, but fundamental connections will be revealed.