We are deep into guessing territory here, but I would think that coarser option (magnesium, phosphorylation states, other modifications, and presence and binding status of other cofactors, especially GTPases) would be sufficient. Certainly for a simulated upload.

No, I don't work with Ed. I don't use optogenetics in my work, although I plan to in not too distant future.

All of it! Coma is not a state where temporal resolution is lost!

You can silence or deactivate neurons in thousands of ways, by altering one or more signaling pathways within the cells, or by blocking a certain channel. The signaling slows down, but it doesn't stop. Stop it, and you kill the cell within a few minutes; and even if you restart things, signaling no longer works the way it did before.

A neuron for Halle Berry, for example, might respond "to the concept, the abstract entity, of Halle Berry", and would fire not only for images of Halle Berry, but also to the actual name "Halle Berry".[15] However, there is no suggestion in that study that only the cell being monitored responded to that concept, nor was it suggested that no other actress would cause that cell to respond (although several other presented images of actresses did not cause it to respond).

Is there any evidece of such large redundancy at the level of biochemical information storage? I'm not aware of it, and I can't see a good reason for such thing to have been evolved.

I'm not a neuroscientist, but AFAIK, I'm not sure that talking about chemical densities is the most appropriate way to frame the discourse here: synapses are small enough that the discrete nature of protein complexes and structures becomes relevant. While disrupting a single molecule wouldn't significantly affect the neuron state, a process that causes generalized misallignment between the active zones on one side and corresponding receptors on the other side, or between the two halves of electric gap junctions, or other widespread distortions, could easily do. Unless this process is reversible in the information-theoretic sense, these bits of information are lost forever.

IIUC, the type of distortions that occur during cryopreservation: membrane deformations due to changes of osmotic pressure and denaturation of cytoskeleton proteins, unfolding of information-bearing proteins, clumping and precipitation out of solution, tend to be irreversible, many-to-one, transitions.

While I agree that this is a relevant consideration for the big picture, I just wanted to note in a non-confrontational way that it has the appearance of unfairly shifting cognitive workload to the skeptic -- which could perhaps result in the nasty side effect of preventing future skeptics from weighing in. Evaporative cooling and all that. A person specializing in synapse biochemistry probably shouldn't have to (at least at first) consider all the aspects of future superintelligence in quite the same way that an AI researcher would.

Just to unpack a little on James_Miller's idea: One example of how this could potentially come into play is that externally gathered data (for example -- chat logs, videos, even the recorded reactions of other humans) could be extrapolated to generate a personality sim, and connectome data could be used to verify it.

Mining data from a lot of different sources, the superintelligence could perhaps get much closer to the original than the mostly-blank, yet connectome matching and genetically identical clone we would otherwise have. Having that matching connectome as a starting point could conceivably be an important part of making sure that the personality matches for the right reasons, i.e. comes out with similar structural-functional mappings.

Again, I'm not sure how much of this maps to the domain specific knowledge that kalla724 has, but I'd be fascinated to hear more.

I don't think any intelligence can read information that is no longer there. So, no, I don't think it will help.

I think you may be missing a silent majority of people who passively judge cryonics as unlikely to work, and do not develop strong feelings or opinions about it besides that, because they have no reason to. I think this category, together with "too expensive to think about right now", forms the bulk of intelligent friends with whom I've discussed cryonics.

kalia724's comment is an apparently-strong argument that I'd never heard, and you know I've actively looked for arguments for and against. I do think you're putting a bit much hope in absence of evidence of criticism as being non-negligible evidence of absence of possible criticism - the space of concepts working scientists don't bother thinking about is ridiculously huge, and cryonics hits quite a few green-ink heuristics (unfairly, IMO, but it does) which gets it filed with the mental spam in short order. edit: and see my Facebook post for a mutual friend of ours noting he has qualms about even writing something serious about cryonics as he risks a significant professional status hit by doing so - cryonics is that low-status.

kalia724 evidently doesn't have time to write this up properly in the foreseeable future, so I think we'd need to ask around to see if there is, at the least, a nameable neuroscientist who thinks kalia's assertions against cryonics have something to them. (I've just hit my socialmediasphere with the question. You, and everyone else interested, probably should too.)

1. Yes, if you can avoid replacing the solvent. But how do you avoid that, and still avoid creation of ice crystals? Actually, now that I think of it, there is a possible solution: expressing icefish proteins within neuronal cells. Of course, who knows shat they would do to neuronal physiology, and you can't really express them after death...

2. I'm not sure that less toxic cryoprotectants are really feasible. But yes, that would be a good step forward.

3. I actually think it's better to keep them together. Trying theoretical approaches as quickly as possible and having an appliable goal ahead at all times are both good for the speed of progress. There is a reason science moves so much faster during times of conflict, for example.

I tried that. Now I'm a whole different combination proteins and chemicals. And this new me doesn't understand how the point you are trying to illustrate relates to the grandparent any better than the old me.

:-D

Take for example:

You can't simply replace unfolded proteins, since their relative position and concentration (and modification, and current status in several different signalling pathways) determines what happens to the signals that go through that synapse

I'm saying such a scrambling happens all the time anyways, and that preserving the exact relative position, concentration, folding status etcetera may not be all that important to the cognitive system at large, at least we don't fret about it when shaking our heads. Does that help?

Edit to respond to your edit:

Is it just tangential expression of your own position on broadly the same subject in loose agreement with Eliezer or is there an additional point you are trying to make?

I'd say it's an important point (naturally). If there were only one-to-one mappings, that would certainly be sufficient to establish that information-theoretically the original state information isn't lost. But that's a red herring, since we don't even need that strong a claim to argue for the theoretical viability of cryonics:

When voluntarily shaking your head (you madman!) you were content with a much, much more forgiving standard. That's the one that should be used for such discussions.

False analogy; there is a change in medium going from the oiled up dermis to air.

Take a glass of water with a large number of tagged proteins. That is the model of e.g. presynaptic vesicles filled with neurotransmitters, swimming in the cytoplasmic matrix (which is mostly water). A significant amount of them is not attached to anything. I didn't say the folding structure would be scrambled, I said that the concentration gradients would be influenced, and that the orientation of non-attached proteins would change.

Shake the glass of water. What happens?

Shake the cytoplasmic matrix. What happens? What does such a rearrangement probably entail? That's right, some change in concentration gradients, and a host of non-attached proteins tumbling around in a merry free-for-all.

Your whole argument is just invalid.

We can arrange to bet on our beliefs about this, say a 4 figure sum going to a charity of the other's choice, with mutually agreed upon authorities in the field being the arbiters? If so send me a PM, and we can make the result public once we're done.

Things don't scale the way you'd like them to.

I'm not sure Kawoomba would really like brains to be scrambled by head shaking. I expect that all else being equal he would prefer as little disruption as possible.

I'm not interested in damage so much as in changes in e.g. "the exact orientation of presynaptic vesicles" not being integral to our personal identity.

If e.g. someone said "we have no scanning techniques that can tell us how exactly each molecule was oriented, it could have been one of many ways (since you're e.g. trying to reverse a non-injective function", I'd say "well, we constantly change that orientation by random body movements, yet don't mind. So we can assume that change is not identity-constituting."

Edit: Even a uniform force will affect soluble elements differently from other elements. The stiffness is different for various body elements, which will lead to all sorts of tiny changes: Erythrocytes being pressed against the cell wall etcetera. That's not a significant change so that we'd say "we leave the elevator a different person", but that's precisely the point in the comparison with certain information that can't be read from a cell: It may not make all that much of a difference.