Connection-Junction: The Synapse.

Connection-Junction: The Synapse. It’s all about networking. Synapses connect nerve cells to each other, or to muscles and glands.

• The word synapse is derived from the Greek syn (together) and haptein (to clasp).

• There are an estimated 100-500 trillion (that’s 10^14) synapses in the human brain.

• The space (synaptic cleft) at the junction is narrow, only 20 nanometers wide.

• Messages travel down the nerve fiber in the form of an electric pulse known as the action potential. When they get to the synaptic terminal, these messages must be converted to a chemical signal that crosses the narrow cleft (within microseconds) to trigger a new electrical signal at the connecting nerve or muscle cell. The chemical signal is the neurotransmitter (glycine, acetylcholine, etc.).

• These chemicals are packaged into small vesicles that lie just under the nerve membrane, docked and ready to fuse. When the action potential arrives, the vesicles execute a quick “kiss and run” to release the neurotransmitter into the cleft.

• Here is a beautiful scanning electron microscope image of a nerve ending in which the membrane has been sheared away, revealing hundreds of spherical vesicles ready to release their neurotransmitter cargo into the synaptic cleft.

• Synapses are targets for hundreds of toxins, psychoactive drugs and poisons including curare, cocaine, LSD and morphine. Botox is a formulation of botulinus toxin, and works by cleaving the proteins that allow the vesicles to fuse. By blocking neurotransmitter release, the nerve cannot signal the muscle to contract. Voila, no wrinkles!

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63 Responses to Connection-Junction: The Synapse.

  1. Oh WOW, another spectacular presentation!

    Thank you Rajini

  2. Rajini Rao says:

    I came across this image and it was just so pretty that I had to write a few sentences to go with it as an excuse to share 🙂

  3. Raijini, I don’t even know how u landed here, what is your field of study/practice?

  4. Tom Lee says:

    Incredibly nice picture Rajini Rao Where is the power source for generating the electrical signals. Chemical reactions may trigger the electrical signals? …Please share your understanding on this as the brain does not need a battery, so to speak.

  5. Rajini Rao says:

    Hi Oskaradrien Tempes , I’m a biochemist by training and my current research is on ion channels and membrane transport. In fact, I have a lecture to teach on action potentials tomorrow, so I’d better go prepare 😉 BTW, I can give you guys a lot more detail/info on this, just ask if you have questions (didn’t want to overload the post).

  6. Omar Saleem says:

    Its spectacular Rajini Rao! Especially when you think about how the synaptic junctions work endlessly being activated and deactivated as nerve impulses travel through.

    Also a shout out to Calcium as one of the key triggers in the synaptic process. #20 is critical!

  7. Rajini Rao says:

    Tom Lee , the immediate power source is the electrochemical gradient of charged particles (ions such as K+, Na+) across the membrane. That gradient, in turn, is set up by ion pumps that use ATP as a power source. When ion channels open transiently, ions run downhill from one side of the membrane to another and change the charge distribution (voltage). A spike in the voltage is (simplistically) an action potential.

  8. It’s al basically a huge wave that fluctuates between an electrical medium and a chemical one.

  9. You should record your lectures and upload them to yoube, I’d totally dig it.

  10. Tom Lee says:

    Rajini Rao Human brain is beautiful and a scientific wonder. Are J.H. and UCSF work together sometimes on brain researches?

  11. Rajini Rao says:

    Sure, Tom Lee , plenty of collaborations between the two institutions..have a neuroscientist colleague at UCSF that I’m planning to work with soon.

  12. How did you land in neuro research?

  13. Rajini Rao says:

    Agree, Jens Darup -pacemaker cells in the heart are pretty cool in that they can generate action potentials by a self sustaining loop. Omar Saleem , thanks for the shout out to calcium….my favorite ion (we work on calcium channels and pumps). Calcium triggers the fusion of the vesicles, as you know 🙂 Oskaradrien Tempes , the genes we were working on turned out to be defective in patients with epilepsy, autism and Angelmans syndrome (a very severe X linked mental retardation). We think they alter the reuptake of neurotransmitter and their packaging into vesicles.

  14. Yup, as the action potential passes near them, the electrostatic activity causes a comformational change in the protein structure, thus opening the gate.

  15. Rajini Rao says:

    Jens Darup , absolutely. Charges lining the pore of the ion channel and the size of the pore itself determine which ions can pass. If you’re interested, take a look at this earlier post where you can see a simulation of a potassium channel opening/closing.

  16. Rajini Rao says:

    Jens Darup , voltage changes are detected by the “gate” in the ion channel, resulting in channel opening. Charges moving through the channel then change the membrane potential. The AP consists of initial depolarization, followed by return to inside negative state of the membrane.

  17. Rajini Rao says:

    Jens Darup Good question! In pacer tissues, there is a non selective leak channel that allows some Na+ to enter, gradually depolarizing the cell. When the potential gets to threshold, voltage gated Na+ channels open and an action potential is triggered. K+ channels bring the potential back to rest and the leak channels once again allow the drift. This drift or leak conductance can be made faster or slower by the autonomic nervous system.

  18. Rajini Rao thanks! I found this very interesting.

  19. Happy New Year Rajini Rao we are learning a lot from your posts. Cheers. 🙂

  20. E Gormley says:

    Spectacular image thanks for sharing!!!!

  21. Rajini Rao says:

    Jim Flanagan , no…but it may well be the Sputnik 🙂

  22. That’s a beautiful photomicrograph, but I also find it a bit creepy.

    Also, it’s sad that brains have to operate on this very inefficient system of action potential -> chemical -> action potential. Imagine how well we’d think if the change in EMF on a cell membrane directly triggered a response in the neighboring neuron! It’s one of my (admittedly unscientific) counterarguments against creationists.

  23. Rajini Rao says:

    Charley Kline , actually, I’ve thought about this too..what if action potentials jumped across the synapse, as indeed they do between Nodes of Ranviers in a myelinated nerve fiber? Here’s what I think. The synapse is actually tripartite…there is also the astrocyte or glial cell that clears away the neurotransmitter before recycling it back to the presynaptic neuron. This equals additional mechanisms of regulation. In nature, it is not only efficiency that matters, but complexity. I’ve said on these posts before, that ion channels can be stunningly simple as with antibiotic ionophores like gramicidin or valinomycin. So why are the channels in our brain so large and complex. It’s for regulation and modulation in so many ways, that we have only seen the tip of the iceberg. Thank you for your thoughts!

  24. E Gormley says:

    From complexity to plasticity to adaptability constrained by environment…

  25. Rajini Rao says:

    I could not have said it better, Beth Gormley !

  26. I’d like to bring some of this scientific discovery and knowledge into my basement workshop to hack on. An organic computer grown in an aquarium sounds like a neat project. Where would an ignorant man start to read to learn enough to judge if doing something like that is a reasonable proposition?

  27. Rajini Rao says:

    Grace Schiavone , it means you “like” it as in FB, only better 😉

  28. ”the genes we were working on turned out to be defective in patients with epilepsy, autism…” Defective in what way?

  29. Rajini Rao says:

    Richard Healy , It takes $$, dozens of new born mice (pups) brains, incubators/equipment/weeks of incubation to grow a dish of neurons. And then they die 🙂 Alternatively, you could keep an electric eel in your basement aquarium to power your lights ..they use the same ion channels in packed arrays to deliver hefty 500 volts of electricity. Electric Eel Powers Christmas Tree

  30. Rajini Rao says:

    Stephen Stillwell , they carried (inherited) mutations that made them nonfunctional.

  31. Think that could alter the efficacy of ssri’s?

  32. Rajini Rao says:

    Possibly. SSRI’s work on serotonin transporters (which can also carry mutations)- the transporters we are studying in the neurons/astrocyte cells (known as sodium/hydrogen exchangers) alter levels of other receptors and channels at the synapse.

  33. Thanks, and for all the interesting stuff.

  34. Gorgeous images! and great information, once again 😉

  35. Rajini Rao, that complexity hypothesis in the context of Darwinian evolution makes total sense. I tend to think of it as “bad design” but I think what you’re saying is that of all the possibilities, the neurotransmitter model with its many complexities (inhibitors, glial cells, ion channels with different atomic ions, recycling times, and on and on) makes up a system with many more “knobs” that can be tweaked by random variation and genetic selection. If I imagine organisms over a billion years random-walking their way to various hilltops in the fitness landscape, it’s easy to see how a very complex model with a ton of variables would get randomly selected for a lot faster than a much more deterministic one where neuronal interconnections worked more like transistors.


  36. Thank you for sharing this, I love being able to see our tiny bits. We’re amazing.

  37. Jaganathan K says:

    Thanks for sharing this! Great!

  38. Great post, Rajini Rao and nice to meet you!

  39. Thanks for the informative post .

  40. Joan Hogol says:

    Very interesting, thank you. And the electric eel video is really amazing too !

  41. Matt Kuenzel says:

    That is a beautiful image. I’m wondering what differentiates the blue from the orange vesicles. I looked for info on how it was stained/colored but couldn’t find anything. And the green (membrane?) appears also to be composed of spherical units.

    Charley Kline raises a really interesting question about the seemingly inefficient neuron to neuron connection.

  42. I take your word, else it does look like a yummy scoop of ice cream!

  43. Rajini Rao says:

    Matt Kuenzel , there’s no functional difference between the orange and blue vesicles..the pseudocoloring is based on the depth of staining. Because the image zooms in on the nerve terminal, the surface membrane (green) shows bumps from the vesicles docked just below. I don’t think it would look like that further away from the terminal.

    Another point about the chemical nature of the synapse that I forgot to mention in my reply to Charley Kline was that the neurotransmitters can modulate the threshold of firing and the strength of transmission to the other neuron. This way you can have inhibitory synapses, that make it harder to fire an action potential (GABA-ergic synapses dampen the response by opening chloride channels and making the interior more negative)..and adjust plasticity/memory/learning.

  44. Matt Kuenzel says:

    Rajini Rao Thanks, even more amazing!

  45. Evolution sure produced some intricate and beautiful, yet inefficient and Rube-Goldberg-esque mechanisms, didn’t it?!

    So what I think of as an electric current passing through the neuron isn’t really that at all, is it? That would be defined as electron transport, and what you’re describing is more like a wave of depolarization traveling down the fiber. It isn’t ever really electrical at all, it’s action potential triggering gate responses all the way. It is very hard for an electrical engineer like me to unlearn so many things!

  46. Rajini Rao says:

    Charley Kline , Real electron transport does indeed occur in the process of cellular respiration in mitochondria…a series of proteins move electrons down their redox potential from a donor (NADH) to molecular oxygen. The energy from this movement is captured in the form of a proton electrochemical gradient which is then harnessed to make ATP. As for the action potential, you are right in that it is a wave of depolarization that travels down the nerve fiber. The cause of the depolarization is the movement of charges through ion channels, which can be detected as currents. In that sense, the signaling is indeed electrical. You may be amused that I try to present an electrical engineers perspective of current voltage graphs to my students just for fun…an ion pump is analogous to a “battery”, voltage-gated ion channels are called rectifiers, and the system follows a modified Ohms Law. 🙂

  47. Tom Lee says:

    +Rajini Rao, as an engineer I can appreciate your explanation regarding this whole process of how the electrical signals are generated and processed , as well as where the voltages and currents are coming from. Thanks for a thorough coverage of this fascinating function of the brain, down to the synapse. Not sure if my next question is within the scope of this discussion, I’m just wondering if this signal is a unidirectional? How does it work in a bidirectional fashion? In other words the feedback to the brain.

  48. Sure, but the mitochondrial electron transport chain (cool as it is, with ATP Synthase running like a little electric motor!) is an energy storage mechanism, more like how a battery is charged than how signals are communicated in a (silicon) processor.

    I think we are just circling around the definition of what “electronic signaling” is, though. I come at it from the standpoint of electrons themselves moving through a conductor from point A to point B and thus generating positive or negative electric fields that in turn do some useful thing. The same end effect (charge imbalances doing something useful) is happening in the neuron, just in a way more complicated way, so I take your point.

    Your analogizing ion pumps and channels to electronic components and laws sounds super-cool, though. I would love to sit in on one of those lectures!!

  49. Gorgeous imagery Rajini. Thank you.

    Sidebar: Sherrington, whose work table I have had the pleasure of working atop in Karl Pribram’s lab, and founder of the synapse, was not so much interested in the synapse itself… but the processing occurring pre- and post-synaptically (the slow-potential processing within the 4-D felt-work of dendrites) as it turns out 🙂 This led ultimately to Pribram, in a moment of free-association at a psycho-perception conference in Europe, to utter out loud the connection to Gabor, Fourier Transforms; the frequency domain and resonances, and finally his first thoughts concerning what became his holographic hypothesis of memory and perception; which then led to his conversations with David Bohm… and then to holonomy and the evolving framework and theory of. A great “path-of-ah-ha.”

  50. Tom Lee says:

    Hmm…Fourier transforms, frequency domain and resonances… sounds familiar. Wondering if they were successful in reconstructing into processed domain…Just a thought! Were they tried to make an MRI picture out of the whole deal?

  51. That would be nice, huh.

    Bu no MRI’s at that time. I left in ’86 and am now working in a field that might be called “micro-evolution” – human, innate, gift-centric (organic dispositional) resonances and their relationship to understanding “Self” consciousness in practical ways and as they can unfold within one’s lifetime (hence “micro” evolution); and related educational ontology and curriculum, and psycho-social apps such a 3-app suite: “The Ah-Ha Tracker”, “The Flo-Tracker” and “The Path-of-Ah-Ha” and of course the correlated future of the Internet and next gen-OS’s.


    I also am cogitating 🙂 quite a bit about what I affectionately enjoy referring to as the coming “Human Singularity” – or the evolution of greater and greater degrees of psycho-social coherence and social wholeness through greater and greater degrees of working human synergy – seen as a natural balancing Hu-based counterpoint to the Tech-Sing that has been getting so much undivided airtime of late.

    I mean, what else is there, really. We are all striving (even here in G+ and to varying degrees of success) for Hu-synergy in parallel with (consciously or not) our striving for insight and knowledge, motivated by our (discovered/developed) innate and natural dispositions (manifest/time,and if we are fortunate, as a YOUnique matrix of talents & abilities), which is further motivated by the yearning to share and constructively-connect and affect our world with synergistically resonant YOUnique others…. it’s all about connecting to others gloriously and only as human beings (our mind/brains) can do. And this I see as a micro-evolutionary process both within each of us as individual “Self’s” and between all of us as a (waiting) potentially synergy rich system as an inherently singular whole (to visualize: think connected, via the vortices, nth-dimensionally nested-toroids).

  52. Tom Lee says:

    J. Brian Hennessy Some techniques you mentioned earlier were actually the computerized fundamentals used in Magnetic Resonance Imaging technology where it is used to take the time domain, which is raw data collecting from Radio Frequency echoes emitted by the Hydrogen protons in human or animal tissues, using FFT (Fast Fourier transforms) to reconstruct into what they call processed domain data for an MRI image. The MRi technology actually was very much alive in 1986. I thought, as reading your comments, that neurophysiology was using the technique for exploring and researching the physiological functions of the brain. Your field of study seems very interesting. Thanks for your feedback!

  53. Thanks Tom. Yep, I see human micro-evolution and the potential for self-evolution as a great coming and manifesting tech/app/OS wave. Indications of our interest in such are seen with emergent movements such as Quantified-Self, Life-Logging, etc, and companies such as and – and of course, “social” as a wavelette and platform for this future.

  54. Rajini Rao says:

    Rens dG they are both presynaptic terminals loaded with synaptic vesicles (little balls seen in the ruptured parts), ready to release neurotransmitter into the cleft. It could be an axon or a dendrite. 

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