A team of researchers in Germany has created a very highly detailed 3D computer model of an individual rat synapse depicting the distribution of approximately 30,000 proteins involved in the process of sending a message from one neuron to another. The below video has cover detail view of the process that take place during information transfer at Synapse
Our brains are full of trillions of synapses, each with the capability of converting an electrical signal into a chemical one and back again.
In their paper published in the journal "Science" the team describes how they combined several imaging techniques to create the model, and what it is able to display.
In simple terms, Neuron transmit messages between one another via synapses—parts of neurons dedicated to converting electrical signals to chemical signals and vice versa.
Synapses are miniscule – nerve terminals are about one thousandth of a millimetre in diameter, and the space between them (cleft) and the membrane they contact a mere 20-40 millionths of a millimetre wide – and are densely packed in the grey matter of the brain tissue, making them notoriously difficult to study.
Inside the nerve terminal, neurotransmitter molecules are stored in tiny spheres called synaptic vesicles, which are "docked" in an "active zone" (depicted as red color in the video) just beneath the cell membrane. When a nervous impulse arrives at the terminal, it causes a few of the vesicles to fuse with the membrane and release their contents. Later on, the spent vesicles are recycled – they are pulled back out of the membrane, re-filled with neurotransmitter molecules, and eventually re-used.
At any given terminal, vesicle fusion can occur hundreds of times per second, as trains of impulses arrive one after the other. The whole process of vesicle docking, fusion and recycling is therefore tightly regulated, to ensure that there is a ready supply of vesicles that can fuse in quick succession and maintain the rapid bursts of neuronal activity.
“Our model shows that the proteins involved in neurotransmitter release can be enormously abundant, with up to 27,000 copies per synapse,” says Silvio Rizzoli, senior author of the study, “whereas proteins involved in recycling are present in only 1,000-4,000 copies.” The high number of vesicle-release proteins isn’t entirely surprising, because nerve terminals are thought to contain hundreds of vesicles docked at release sites."
For instance, that green guy, parvalbumin, in certain neurons that protein seems to trigger high-frequency brain waves that have been linked to cognition. And that red SNAP-25 has been linked to ADHD, and the yellow VDAC has been proposed as a good target for chemotherapy drugs.
To create the model, the Researchers isolated rat brain neurons and used mass spectrometry, electron microscopy, super-resolution fluorescence microscopy and antibody staining to get different looks at the sending synapse.
In so doing they were able to determine the number of 62 different proteins involved in the recycling process and where they belong in the synapse. That allowed them to build a model able to depict how the synapse actually looks during each stage of the process—a feat that will undoubtedly help many other Neuro-scientists as they seek to better understand how the brain is able to do all the things it does & various Brain Disorder
(Video credit: Wilhelm et al. 2014, Science)
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Synaptic vesicle recycling has long served as a model for the general mechanisms of cellular trafficking. We used an integrative approach, combining quantitative immunoblotting and mass spectrometry to determine protein numbers; electron microscopy to measure organelle numbers, sizes, and positions; and super-resolution fluorescence microscopy to localize the proteins. Using these data, we generated a three-dimensional model of an "average" synapse, displaying 300,000 proteins in atomic detail. The copy numbers of proteins involved in the same step of synaptic vesicle recycling correlated closely. In contrast, copy numbers varied over more than three orders of magnitude between steps, from about 150 copies for the endosomal fusion proteins to more than 20,000 for the exocytotic ones.