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First, although I was always taught that the axon and a dendrite were separated by a synaptic gap of about 20 to 40 nm, I recently saw a reference I've since lost that seemed to suggest we've found that not all axon-dendrite pairs have literal gaps between them; some touch. Unfortunately, I didn't have time to read it, I have not recovered the source, and a search hasn't yet helped. Is there research that suggests that some axons and dendrites actually touch?

Second, what exactly is in the gap? Liquid, gas, nothing/vacuum? Of course, neurotransmitters can cross the gap, but I'm asking about whether something's always in the gap and if so what.

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See a previous Q&A:

How synapses are hold in place if they're not phisically attached?

Synapses are quite structured, and there are physical connections between pre- and post-synapse through adhesion molecules, but the membranes themselves do not quite touch. Cell membranes are a phospholipid bilayer; the outside is hydrophilic and has a bit of a charge, so typically membranes won't sit right against each other, they'll always have at least a 'shell' of water in between. If they were held more closely, they would fuse, like happens with vesicles.

The gap is filled with extracellular fluid: mostly water, with dissolved salts and molecules. Released neurotransmitters cross the synaptic cleft by diffusion.

There are some synapses referred to as "electrical" synapses rather than chemical synapses; these are pretty much the same physically, except there are protein pores between the membranes that allow diffusion between their respective intracellular spaces. Everywhere else there'll be a gap. I'm not sure what you were reading about synapses without a gap, but maybe this is what they meant - I wouldn't quite describe it that way, though.

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  • $\begingroup$ Yes, this is just what I needed. And I do think it was a (science writers?) reference to electrical synapses that I was vaguely remembering. I just found ncbi.nlm.nih.gov/pmc/articles/PMC5705454 which mentions that many in neuroscience think of electrical synapses in mammals and humans as recently discovered. Thank you, Bryan! $\endgroup$
    – Anasker
    Oct 20, 2022 at 20:20
  • $\begingroup$ @Anasker Knowledge of their existence is not particularly new, at least compared overall to the field of neuroscience that with a handful of exceptions is itself quite new (the word 'neuroscience' itself I believe was first used in the 1970s). But yes, I would say their functional roles tend to be underappreciated and often left out of broader discussions. $\endgroup$
    – Bryan Krause
    Oct 20, 2022 at 20:26
  • $\begingroup$ Yes, the article says we knew of them mid-century, but: "To many established scientists in the neuroscience community who are uninitiated with respect to the many decades of literature on electrical synaptic transmission, the field of electrical synapses in mammalian systems may appear to have emerged suddenly at the beginning of this century, with the subsequent pace of progress in the area being nothing short of astonishing." Leaves open how many are "uninitiated". Thanks again. $\endgroup$
    – Anasker
    Oct 20, 2022 at 20:35

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