One of the most complicated and fascinating challenges for the neuroscientists is how to link the architecture, the wiring and the electric messages of the neuronal circuits to our behavior and emotions. To date, the desire of understanding this correspondence is simply unrealistic: the reason lies in numbers.
302: is the number of neurons that form the nervous system of the worm Caenorhabditis elegans. This circuit has been completely mapped.
15,000: are the neurons in the brain of a fruit fly maggot (the well-known Drosophila).
135,000: are the neurons in the brain of an adult fruit fly.
71,000,000: are the neurons of a house mouse.
86,000,000,000: are the neurons of a human brain.
30: is the number of neurons of a simple circuit system in the crab gastric system. And, after decades of investigation, no one has completely understood how it works yet.
To make the challenge even more complicated, each neuron interacts with many other neurons through a web of synapses that increases exponentially the number of possible connections.
Moreover, any brain circuit involved in a specific reaction, for example, the reaction to an olfactory stimulus, not only involves a large number of neurons but, as if it wasn’t enough, the reaction to the same stimulus may proceed from the activation of different circuits.
So, the complexity of a simple circuit may be projected to the overwhelming complexity of a human brain while writing an article, watching the rain out of the window, listening to the radio, smelling a bag of peanuts and picking one of them – all at the same time. The temptation of explaining which circuits are activated, how they interact, and maybe of predicting the resulting behavior of a person is hard to explain with numbers. Quoting the words of a scientist trying to explain the amount of data needed to map the whole brain of a mouse, “It’s going to be astronomical numbers. I don’t even know if there is a word to describe this. It’s beyond petabytes. Petabytes of petabytes”. One petabyte is 1015, i.e. a 1 followed by 15 zeroes. Petabytes of petabytes… well, it’s hard to even figure out how many zeroes of computational capacity are needed.
But this stunning complexity can easily get worse. Scientists are used to comparing a statistical significative number of samples in order to accept or reject a hypothesis. This means that an n number of brains has to be multiplied to the petabytes of data, then a correlation among them has to be found…
Now, if you are not scared and willing to keep reading, let’s get back to manageable numbers, specifically to the 15,000 neurons of the fruit fly maggot. Pioneers of brain circuits studies like Marta Zlatic try to get the work simple by focusing their attention on small parts of the brain responsible for a specific function, for example a region of 160 neurons involved in the detection of the smells, or another small region responsible for turning or retracting the head in response to an annoying external stimulus.
The figure schematizes the process followed by the scientists: a specific section of the brain is cut in thousands of thin slides, that are analyzed by electronic microscopy. Then, a 3D map containing all the identified connections of each neuron is created. The aim is to discover, after giving an electric impulse, which circuits are activated and which behavior is showed depending on which circuit is in an ON state.
Joining different maps allows to add pieces to the puzzle, and comparing similar pieces of different puzzles can give the possibility to figure out which circuit patterns are conserved and which are variable, as Zlatic’s team is starting to see in some portions of the brain of the fruit fly maggots.
The importance of mapping the brain circuits could help to give some answer to medical issues. For example, it could be explained why some drugs are effective in some people and not in others, as it occurs in Parkinson’s disease patients.
So far, scientists have just a small and partial information, but when the effort of the laboratories around the world will start to connect a piece of the puzzle to another, the hope of a better understanding of the extraordinary complexity of the circuits of the brain will move some more steps towards the final goal: the real understanding of the brain processes underlying the human behavior.
Smith K. How to map the circuits that define us. Nature. 2017 Aug 9;548(7666):150-152. Available online at 10.1038/548150a
The elaboration of this post has been financed by the project PI15/01082, as a part of the National Plan of I+D+I and co-financed by the ISCIII – General Deputy Direction for Evaluation and Development of Health Research – and the European Regional Development Fund (ERDF).