Source: 3D reconstruction of the olfactory bulb of a zebrafish larva. Credit: R. Friedrich, Friedrich Miescher Institute for Biomedical Research/ Used by premission

How does the brain process information? How does information processing take us from the low-level information we extract from to our complex and rich experience of the world around us?

Imaging technologies like fMRI give us a good idea of where in the brain different types of information are processed but they don’t tell us how that information is being processed. Although our understanding of what is happening at the synapse has increased greatly, organized collections of neurons, not single neurons, are the key functional units of information processing.

In general terms, we know that organized collections of neurons receive input, do something with it, and output the result to other collections of neurons. Information processing in the brain takes place through extended sequences of these input-processing-output interactions among collections of neurons. The problem is trying to figure out exactly which collections of neurons are providing the input, what information is contained in the input, what a particular collection of neurons does with the input, and which collections of neurons are getting the subsequent output.

It’s a very difficult problem for many reasons. Individual neurons are densely packed in small areas and each neuron can have up to tens of thousands of synaptic connections with other neurons. The organized collections of neurons that we are trying to understand may be composed of tens, hundreds or even thousands of individual neurons.

Part of what is needed is something like a wiring diagram of the brain that lays out which collections of neurons are communicating with other collections of neurons. In other words, we need a neural map that captures functionally organized collections of neurons at the level of the synaptic connections between individual neurons.

One of the many factors that makes creation of this map difficult is that there is an enormous difference in scale between the cubic millimeter volumes of neural tissue that are needed to capture an organized collection of neurons and the nanometer-level resolution that is needed to capture the individual synaptic connections between neurons. Millimeters are six orders of magnitude larger than nanometers. Six orders of magnitude is a size differential that is almost impossible to grasp in the abstract. In terms that are easier to understand, finding an individual synapse in a cubic millimeter of nerve tissue is like looking for a sewing needle in a haystack – when the haystack is roughly the size of Los Angeles and is about 23 miles high.

Fortunately, 3D electron microscopy is capable of capturing images with nanometer-level resolution in cubic millimeter sized tissue samples. A team of researchers at the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland developed new methods for use with 3D electron microscopy and demonstrated the effectiveness of their methods with a reconstruction of the bulb of a zebrafish larva. They published their findings in the April 2016 Volume of Nature Neuroscience.

Their 3D reconstruction captured approximately 98% of the 1047 neurons in the olfactory bulb. Connection patterns for individual neurons were dense and widespread throughout the olfactory bulb but they were not random. The researchers were able to identify collections of interconnected neurons that received input from olfactory sensory neurons that respond to specific odors. In addition, they found that the output from these organized collections of neurons was routed to different substructures in the olfactory bulb.

The researchers succeeded at identifying the kind of organized collections of neurons that are believed to be the key functional units of information processing in the . They were also also able to map the input and output connections of these organized units at the level of individual neurons. In other words, they provided just what we need - a basic wiring diagram of a complex neural structure.

The olfactory bulb of a zebrafish larva is a long way – a very long way – from the human brain. In addition, the 3D electron microscopy and data analysis techniques developed by the researchers and used in the study are not easy to carry out although they are improvements over other methods. This research isn’t going to result in a complete wiring diagram of the human brain anytime soon. However, it appears to be a step in the right direction that has the potential to lead to further discoveries in our ongoing attempts to understand how the brain processes information.