The human brain is truly awesome.
A typical, healthy one houses some 200 billion nerve cells, which are connected to one another via hundreds of trillions of synapses. Each synapse functions like a microprocessor, and tens of thousands of them can connect a single neuron to other nerve cells. In the cerebral cortex alone, there are roughly 125 trillion synapses, which is about how many stars fill 1,500 Milky Way galaxies.
This is a visual reconstruction from array-tomography data of synapses in the mouse somatosensory cortex, which is responsive to whisker stimulation.
(Credit: Stephen Smith/Stanford)
These synapses are, of course, so tiny (less than a thousandth of a millimeter in diameter) that humans haven't been able to see with great clarity what exactly they do and how, beyond knowing that their numbers vary over time. That is until now.
Researchers at the Stanford University School of Medicine have spent the past few years engineering a new imaging model, which they call array tomography, in conjunction with novel computational software, to stitch together image slices into a three-dimensional image that can be rotated, penetrated and navigated. Their work appears in the journal Neuron this week.
To test their model, the team took tissue samples from a mouse whose brain had been bioengineered to make larger neurons in the cerebral cortex express a fluorescent protein (found in jellyfish), making them glow yellow-green. Because of this glow, the researchers were able to see synapses against the background of neurons.
They found that the brain's complexity is beyond anything they'd imagined, almost to the point of being beyond belief, says Stephen Smith, a professor of molecular and cellular physiology and senior author of the paper describing the study:
One synapse, by itself, is more like a microprocessor--with both memory-storage and information-processing elements--than a mere on/off switch. In fact, one synapse may contain on the order of 1,000 molecular-scale switches. A single human brain has more switches than all the computers and routers and Internet connections on Earth.
Smith adds that this gives us a glimpse into brain tissue at a level of detail never before attained: "The entire anatomical context of the synapses is preserved. You know right where each one is, and what kind it is."
While the study was set up to demonstrate array tomography's potential in neuroscience (which is starting to resemble astronomy), the team was surprised to find that a class of synapses that have been considered identical to one another actually contain certain distinctions. They hope to use their imaging model to learn more about those distinctions, identifying which are gained or lost during learning, after experiences such as trauma, or in neurodegenerative disorders like Alzheimer's.
In the meantime, Smith and Micheva are starting a company that is gathering funding for future work, and Stanford's Office of Technology Licensing has obtained a U.S. patent on array tomography and filed for a second.
This four-minute video explores the pial (outer) surface of a mouse's cortex through all six layers and subcortical white matter to the adjoining striatum: