Brain complexity: mapping circuits (Introduction)

by David Turell @, Wednesday, August 09, 2017, 19:30 (12 days ago) @ David Turell

Turns out to be a very difficult task so tiny brains are used, such as fruit fly larva:

"her fly larvae can be made to perform 30 different actions, including retracting or turning their heads, or rolling. The actions are generated by a brain comprising just 15,000 neurons. That is nothing compared with the 86 billion in a human brain, which is one of the reasons Zlatic and her teammates like the maggots so much.

“'At the moment, really, the Drosophila larva is the sweet spot,” says Albert Cardona, Zlatic's collaborator and husband, who is also at Janelia. “If you can get the wiring diagram, you have an excellent starting point for seeing how the central nervous system works.”


"And the resulting neural-network diagrams are yielding surprises — showing, for example, that a brain can use one network in multiple ways to create the same behaviours.

"But understanding even the simplest of circuits — orders of magnitude smaller than those in Zlatic's maggots — presents a host of challenges. Circuits vary in layout and function from animal to animal. The systems have redundancy that makes it difficult to pin one function to one circuit. Plus, wiring alone doesn't fully explain how circuits generate behaviours; other factors, such as neurochemicals, have to be considered. “I try to avoid using the word 'understand',” says Florian Engert, who is putting together an atlas of the zebrafish brain at Harvard University in Cambridge, Massachusetts. “What do you even mean when you say you understand how something works? If you map it out, you haven't really understood anything.” (my bold)

"Still, scientists are beginning to detect patterns in simple circuits that may operate in more complex brains. “This is what we hope,” says Willie Tobin, a neuroscientist at Harvard Medical School in Boston, Massachusetts: “that we can come across general principles that can help us understand larger systems.”


"For 30 years, neuroscientist Eve Marder of Brandeis University in Waltham, Massachusetts, has been working on a simple circuit of 30 neurons in the crab gastric system. Its role is simple and the wiring diagram has been in hand for decades. Still, the circuit has mysteries to offer. Marder has shown, for instance, that although the circuits of individual animals may look the same and produce the same output, they vary widely in the strength of their signals and the conductance at their synapses.


"Then, in Cardona's lab, scientists worked through mapping the larval brains, compiling thousands of images of brain slices taken with electron microscopes and painstakingly tracing the connections between neurons. This map forms the starting point for the rest of their efforts — map the circuit, manipulate the circuit, watch the behaviour (see 'Connecting the dots'). On page 175, the team uses this protocol to reveal how a circuit in the Drosophila brain called the mushroom body controls learning and memory, by linking feelings of reward or punishment with sensory information7. But the mapping process is a big hold-up in the field right now, Cardona says. Reconstructing a 160-neuron portion of the fly smell-detection circuit for another paper8 took Cardona's team more than 1,100 hours. One estimate9, extrapolating from previous fruit-fly work, suggests that a map of the full adult fly brain would take hundreds of person-years to complete. Automating the process would help, but algorithms can add bogus connections or miss some entirely. (my bold)


"Those working on larger circuits often break the problem down — assembling a list of cell types first. The Mouse Brain Connectivity Atlas at the Allen Institute for Brain Science in Seattle, Washington, is taking this approach. In work published in 2014, the team identified10 49 types of cell in the mouse visual cortex alone; the cells vary in size and shape, how fast they fire and what genes they express. The team expects orders of magnitude more cell types across the whole brain. “Up to 10,000 neuronal types would be my guess,” says Hongkui Zeng, who works on the atlas at the Allen Institute.


"For now, at least, many researchers are content to embrace the dizzying complexity of the task at hand. Zlatic takes some comfort in the fact that she is starting to see repeating patterns in how neurons in her fly larvae arrange themselves and how they create feedback loops. This modular arrangement, she says, could make the going easier once the team has a finished map. “When you have partial information it looks like a big mess,” she says. “Maybe the most surprising thing is that once you start seeing a relatively complete system, how much sense it makes.'”

Comment: Mapping small circuits is a fine beginning but it still misses the nuances of the individual neuron and its specific input, the way it controls its synapse output, the size and speed of the ion charge. The fMRI studies give general ideas, but the nitty-gritty is at a layer below the circuits being outlined. Note my bolds above. Neural circuits of brains show design in a way no other biological organ can.

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