Two high-speed electronic microscopes 7,062 brain slices. 21 million images. For the first time, we can now drag the brain of the fly to the nanoscale thanks to scientists from the Janelia research campus at the Howard Hughes Medical Institute.
The work required the collaboration of dozens of neuroscientists, mechanical engineers and software developers from Janelia, as well as engineering consultants and scientists from Johns Hopkins University and the MRC Molecular Biology Laboratory.
With this immense operation with visual data, researchers have now traced the paths of neurons (colored threads) that extend to the ‘body of the fungus’, a region involved in memory and learning.
Despite its size, about the size of a poppy seed, the brain of the fruit fly contains about 100,000 neurons (humans have 100 billion). And it has never generated an image of the entire brain of the fly with this resolution that allows you to see the connections between the neurons. This level of detail is key to tracing the circuits of the brain: the precise neural networks that support specific behaviors of flies.
Each neuron branches into a burst of thin wires that touch the wires of other neurons. Neurons communicate with each other through these points of contact, or synapses, forming a dense network of communication circuits. Scientists can see these wires and synapses with an imaging technique called serial section transmission electron microscopy.
To achieve this, heavy metals were first added to the brain of the fly. These metals accumulate in cell membranes and synapses, and ultimately mark the contours of each neuron and its connections. Then, the researchers hit the slices of the brain with an electron beam, which goes through everything except the metal-laden parts.
But taking 21 million images would be very slow, it would take decades. However, the team developed new tools to accelerate the process using high-speed cameras and two custom systems to quickly move tissue samples in eight-micrometer increments, allowing them to quickly capture images of neighboring areas.
They were able to obtain an image of a whole brain slice in less than seven minutes, five times faster than the previous high-performance transmission electron microscope camera matrix, TEMCA1. They also benefited from a custom robotic loader built in Janelia that automatically collects and places samples.
Now, more than 20 lab groups are exploring the new data set, tracking neurons and delineating brain circuits.