Comment by dale_glass

I don't think there's anything we can simulate "completely", in the sense that a fire-and-forget model would subsequently go onto have a typical life.

The stomatogastric ganglion might be the closest. It is a network of three dozen neurons in the crustacean stomach. Like the worm, the wiring diagram is completely known and the physiology is easier to measure. Despite being very simple, it can generate intricate patterns of activity in the stomach muscles that let the crab/lobster/etc eat. Scholarpedia has the diagram and some references (http://www.scholarpedia.org/article/Stomatogastric_ganglion) Eve Marder, who has done a lot of pioneering work on this circuit, wrote a book (Lessons From the Lobster) that I'm looking forward to reading.

Don't be disappointed! A lot of media coverage tends to present new results as "we're almost there." In most cases, I think that's nonsense, but it's also exciting to think how many things there are left to discover and how fascinatingly complex the world is.

c. elegans is pretty much the only one we fully mapped. (Possibly some fish larvae, too? Recall fuzzy)

But given that we can't even fully simulate animals with exactly zero neurons (Trichoplax), I'd say the current limit is "we can't". It's literally the world's simplest animal, and we're far from understanding how it works.

So, probably no brain uploads by 2031 ;)

I’m not sure how to put a reasonable number on it, especially the simulation part, but C. elegans is a very common model organism. It’s maybe not as well-known as mice or rats, but probably in the top ten most-studied organisms. Here’s a nice review (https://www.nature.com/articles/nrg2105); a quick glance at the WormBook might also give you a sense for the breadth and depth of what’s been done[0]. http://www.wormbook.org/

Neurotransmission in C. elegans is unusual. They use a different set of neurotransmitters; this isn’t that odd—-insects also use a slightly different set than humans, and their role even flips in many animals (including mammals) during development. The weirder part is what those neurotransmitters do. In other animals, neurons produce stereotyped all-or-none “spikes” of electrical activity. Until quite recently, it was unclear whether C elegans neurons did too. This News and Views (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951993/#R29) does a nice job describing plateau potentials and the reasons that C. elegans neurons might differ (namely, they’re very small). A few years later Cori Bargmann’s group discovered that the AWA neuron fires something more akin to a “classical” spike—-sometimes. It also uses calcium instead of sodium. https://www.cell.com/cell/fulltext/S0092-8674(18)31034-1

This might complicate simulations a little bit, but these differences are also understood pretty well, and the much smaller nervous system more than offsets them.

[0] I work at the polar opposite end of neuroscience—-large animal neurophys—-but I’ve always been a little jealous of how friendly and tight-knit the C elegans community seems. They have a lot of great open resources.

Of course!

The observation that one neuron can alter the activity of a nearby one is old as dirt. Emil du Bois-Reymond observed it in the late 19th century, but I don't know of anyone trying to quantify it until Katz and Schmitt (1940) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1393925/ and Angelique Arvanitaki (1941) https://journals.physiology.org/doi/abs/10.1152/jn.1942.5.2...., who named it. There are some other reports in squid (Ramon & Moore, 1978) https://pubmed.ncbi.nlm.nih.gov/206154/, rat cerebellum (Korn and Axelrad, 1980) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC350252/, and others. This review by Anastassiou et al. (2011) might be a good place to start https://www.nature.com/articles/nn.2727.pdf?origin=ppub or this Scientific American article about a paper by my grad school neighbors (https://www.scientificamerican.com/article/brain-electric-fi...)

In parallel, people have asked whether external electric fields can be used to alter neurons' activity, which is even older: a Roman physician in 46 reportedly cured headaches by applying a live electric fish to patients' heads. The idea of using electricity to improve mental function has waxed and waned ever since, with the most recent peak around ~2015 or so. Terzuolo and Bullock collected some of the first data on this using crayfish axons in 1956 (https://www.pnas.org/content/42/9/687) and subsequent experiments by Deans et al. (2007), Radman et al. (2007-9), Ozen et al. (2010), and Frolich and McCormick (2010) found similar results using in vitro and small animal experiments. In parallel, people went absolutely wild with human studies of transcranial electrical stimulation (TES), a family of techniques including tDCS (w/ direct current) and tACS (alternating current). While some of the results have been exciting, they have not always been reproducible (Horvath et al, 2015ab) and some work suggested that the previous work relied on fields much stronger than those achievable in humans (Voroslakos et al, 2018).

Together with some awesome collaborators, I set up a non-human primate model that let us test tES under conditions that closely match those found in humans: like macaques (and unlike rodents), we have big, convoluted brains in thick bony skulls and comparatively sparse neural networks. We found that tDCS could affect neural circuits (i.e., LFP oscillations) and behavior (Krause et al., 2017) https://www.cell.com/current-biology/pdfExtended/S0960-9822(... and single neurons, even in deep brain areas (Krause, Vieira, et al. 2019) https://www.pnas.org/content/116/12/5747.abstract [0] The fields we used were much weaker than those produced by some parts of the brain itself (~0.3 - 1 V/m vs ~4-8+ V/m), so it suggests that ephaptic mechanisms are probably pretty common.

I'm pretty confident in those results, but--to bring things back to the original topic--our recent experiments suggest that getting tES to do exactly what you want, when and where you want it, will take some cleverness and a lot of simplifying assumptions tend not to hold up.

[0] The missing full references above are in these two articles' bibliographies.