This is a very good question and it’s no easy matter to find a straightforward answer. The best so far is by the anonymous Johns Hopkins neuroscience student—collapsed, ironically, because the contributor’s identity couldn’t be verified.
First of all, let me surmise that the question arises because of fanciful illustrations of brain tissue like these. They depict neurons as if they were surrounded by a sea of unoccupied space, which is highly misleading. One can and should, indeed, wonder what holds those synapses together. The eminent 19th-century pathologist Rudolf Virchow himself wondered about this, and thought the nervous system must have some sort of connective tissue to hold everything in place. He went searching for it and found the brain stuffed with non-neuronal cells; I think it was he who named them neuroglia, glia meaning “glue.” Neuroscientists often say (as do my own textbooks) that they outnumber neurons 10:1 and fill this space, but this ratio now appears to be overstated (and Quora has me thinking I may need to revise that now) [1].
Yet despite the “nerve glue” name, it is not the neuroglia that keeps the synapses from falling apart. We’ve kept the name neuroglia, but we don’t think of it as a glue or adhesive anymore.
Let’s examine the conjecture, offered by one user, that the neurons and glia are simply so densely packed, like a Japanese subway car, that there’s no room to move and the synapses simply can’t fall apart. There may be some truth to that. Here are some colorized electron micrographs of synapses. You can see that the neurons are, in fact, densely surrounded by other cells, really packed in there with little or no room to move. This is the reality disregarded by the artists. The brain simply doesn’t have the empty space that they depict. Artists have a conceptual job to do and they just leave out all the “clutter” so it doesn’t detract from their key point. But that clutter is important.
Even so, I don’t find the packing hypothesis a satisfactory answer either. Dense packing alone isn’t enough to ensure the precise alignment of presynaptic and postsynaptic cells necessary for synaptic function—such as holding synaptic vesicle release sites directly across from neurotransmitter receptor sites on the other cell. The packing hypothesis is like thinking you could build a cell phone just by lining up the electronic components so they were touching as needed, then spraying foam on the circuit to solidify and hold them in position, hoping that the whole thing would hold together over years of use. That’s not going to happen, any more than just packing a bunch of other cells tightly against the synapses will hold them together for a lifetime.
This brings us to the astute answer by our anonymous Hopkins student, the one that sent me down the Google Trail where I found the most satisfactory information. Throughout the body, cells and tissues are held together by cell-surface proteins and glycoproteins (protein-carbohydrate complexes) called cell-adhesion molecules (CAMs). CAMs keep the muscle cells of your heart from pulling apart with every heartbeat, prevent the lining of your esophagus from being scraped away by every bite of food you swallow, toughen your epidermis against all the insults it must endure through your life, bind sperm to egg, and so forth.
Illustrations of synapses—especially ones like the artistic renditions above and even the illustrations in my own textbooks—tremendously exaggerate the width of the gap between the two neurons, the synaptic cleft. We have to, in order to draw in the events that occur there. You get a better impression of that gap from the electron micrographs above. Even then, keep in mind that cells and tissues shrink when prepared for microscopy with the various fixatives and dehydrating agents histologists use, so the gap in those micrographs is even wider than it is in life. (This is called a fixation artifact—an unnatural appearance created by the scientist’s manipulations.) Synaptic clefts are typically about 20 nanometers wide. That’s a more meaningful number when we put it in perspective; the cell (plasma) membrane of each neuron is about 7.5 to 10 nm wide, so the cleft is barely twice as wide as a single cell membrane.
Furthermore, the cleft isn’t empty, either. It’s filled with proteins and glycoproteins of various functions—the fuzzy stuff that I’ve marked with red arrows in these two photos. (The photo on the left shows some shrinkage artifact; the intercellular material fills the cleft more fully than that image suggests.) The reality of the synaptic cleft is far, far different from the lower right image in my first set of figures, the one with the crimson neurotransmitter molecules being released. Most of the proteins in the cleft are of still-unknown functions, owing to daunting technical difficulties in figuring them out [2].
Two of the best understood, however, are the neurexins (Nrxns) and neuroligins (Nlgns) mentioned by the Hopkins student—the point where I’ve learned something new by answering this question, and may even revise a textbook or two because of it. During synapse formation (synaptogenesis), the presynaptic neuron (left, in the figure below [2]) synthesizes neurexins and installs them in its synaptic membrane, while the postsynaptic neuron does the same with neuroligins.
Neurexins and neuroligins form linkages across the gap that align the two cells and hold them in alignment for the rest of the life of the synapse (see box in the above figure). The next image (also from [2]) shows how these proteins link up on a more molecular scale. The very top and bottom of the figure, above and below the gray membranes, are the interiors of the two neurons. The space in the middle where the Nrxns and Nlgns tangle together is the synaptic cleft.
Other mechanisms bring neurons together to form synapses during embryonic and later development, but the new synapses are stabilized by the neurexins and neuroligins. “Without [them], synapses assemble, but do not work properly” [2]. These linkages form not only in embryonic development but throughout life, since we tear down synapses and build new ones as long as we live, creating and removing, strengthening or weakening circuits for memory, motor skills, sensory processing, and so on—overall called synaptic plasticity.
Neurexins and neuroligins provide far more than mechanical linkage, though. They play active physiological roles in synaptic communication. Quoting from Südhof’s abstract [2]:
Neurexins and neuroligins are synaptic cell-adhesion molecules that connect pre- and postsynaptic neurons at synapses, mediate trans-synaptic signaling, and shape neural network properties by specifying synaptic functions. In humans, alterations in neurexin or neuroligin genes are implicated in autism and other cognitive diseases, connecting synaptic cell adhesion to cognition and its disorders. Thus, neurexins and neuroligins are core components of the molecular machinery that controls synaptic transmission and enables neural networks to process complex signals.
Südhof remarks on the importance of precise synaptic alignment by these two proteins, and mutations that render these connections defective, to understanding disorders such as autism, schizophrenia, and Tourette syndrome.
As a bit of related trivia, neurexins were discovered by looking for the mechanism by which black widow spider venom, latrotoxin, triggers a massive release of neurotransmitters at synapses. Neurexins are the latrotoxin receptors. This is a nice example of how important, far-reaching discoveries come from inquisitive investigation of seemingly unrelated questions; how “pure science” can lead to discoveries with surprising ramifications and applications to human self-understanding. Who would have imagined that searching for the binding site of a spider venom would lead to molecular understanding of important aspects of autism or schizophrenia?
Another trivia bit: the neuroligin genes are on the X sex chromosome, underscoring the point that most X-linked genes have nothing to do with sex.
Thanks for the thought-provoking question, and thanks to the Hopkins person for the lead to neurexins and neuroligins. I gave my synapses a workout, doubtlessly employing my own neurexins and neuroligins, and I learned something important this morning from you. I hope that’s mutual.
References
- C. S. von Bartheld, J. Bahney, and S. Herculano-Houzel. 2016. "The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting". The Journal of Comparative Neurology. 524 (18): 3865–3895. doi:10.1002/cne.24040. ISSN 1096-9861. PMC 5063692. PMID 27187682.
- T. C. Südhof. 2008. Neuroligins and Neurexins Link Synaptic Function to Cognitive Disease. Nature 455:903–911.
- All images not otherwise credited are from Google Images.