Sunday, March 26, 2017
The brain up close: Radical microscope reveals nerve synapses firing in breakthrough that could shed light on Alzheimer's and depression
The closest view yet of multiple working synapses. Using a custom-built microscope, the scientists achieved the closest view yet of working nerve synapses - the junctions between neurons that dictate how they communicate. The image is color coded, where brighter yellow spots represent multiple vesicle releases at different synapses. This image was obtained following extensive simulation of vesicle release while using a fluorescent marker
Until now, close-up views of neuron synapses have been provided by electron microscopes, which require the cells to be dead.
But the researchers built a custom-built microscope with a sensitive camera to analyze living, working neurons up close.
The brain hosts a complex network of interconnected nerve cells that are constantly changing electrical and chemical signals at high speeds.
Researchers at the Washington University School of Medicine in St Louis studied synapses - the junction between neurons that allow them to communication with each other.
Studying synapses is important for understanding brain networks and how diseases such as depression and Alzheimer's affects the brain, the researchers said.
'Synapses are little nanoscale machines that transmit information,' said senior author Dr Vitaly Klyachko, an associate professor of cell biology and physiology at the School of Medicine.
'They’re very difficult to study because their scale is below what conventional light microscopes can resolve.
'So what is happening in the active zone of a synapse looks like a blur.
'To remedy this, our custom-built microscope has a very sensitive camera and is extremely stable at body temperatures, but most of the novelty comes from the analysis of the images.
'Our approach gives us the ability to resolve events in the synapse with high precision,' he said.
A synapse consists of a tiny gap between two nerves, with one nerve serving as the transmitter and the other as the receiver.
When sending signals, the transmitting side of the synapse releases little packages of neurotransmitters, which traverse the gap and bind to receptors on the receiving side, completing the information relay.
On the transmitting side of the synapse the neurotransmitters at the active zone are packaged into synaptic vesicles.
The active zone is the area where the neurotransmitter is released from.
Until now, close up views of the active zone have been provided by electron microscopes.
They work by bombarding objects with electron beams instead of light.
While they offer resolutions of tens of thousand of nanometers - around 1,000 times thinner than a human hair and smaller - they can't view living cells.
To withstand being bombarded by electrons, the samples must be fixed in an epoxy resin or flash frozen, cut into thin slices and coated in a layer of metal atoms.
'Most of what we know about the active zone is from indirect studies, including beautiful electron microscopy images,' said Dr Klyachko.
'But these are static pictures.
'We wanted to develop a way to see the synapse function.'
The researchers wanted to find out if there are many places on the neuron's active zone where vesicles can release its neurotransmitter into the gap to send a message to another neuron.
The researchers said indirect measurements suggest there might be only one, or maybe two or three of these sites, at most.
This idea can be compared to a shower head: Does the neuron function as a single jet or as a rain shower?
Dr Klyachko and first author Dr Dario Maschi, a postdoctoral researcher in Dr Klyachko's lab, found that the active zone is actually more like a rain shower.
But it isn't random - there are about 10 places across the active zone that are reused often for releasing neurotransmitter.
But there's a limit to how quickly the sites can be reused - about 100 milliseconds must pass before an individual site can be used again.
When the neurons are sending messages at a rapid rate and many vesicles are released, site usage tends to move from the center to the edges of the active zone.
'Neurons often fire at 50 to 100 times per second, so it makes sense to have multiple sites,' Dr Klyachko said.
'If one site has just been used, the active zone can still be transmitting signals through its other sites.
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