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Researchers have recently identified "engrams" in the mouse hippocampus, "sparse populations of neurons" or "small clusters of cells", stimulation of which elicits a specifically trained fear memory association. For example...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874022/

http://www.nature.com/nature/journal/v484/n7394/full/nature11028.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331914/

http://www.smithsonianmag.com/innovation/meet-two-scientists-who-implanted-false-memory-mouse-180953045/

My question: Roughly how big -- how many neurons -- are the regions stimulated in these experiments? I looked through a number of papers and was unable to find this information.

10/18 -- Changing the title and wording to clarify that I am asking just about experimental procedures with electrode implants, not fMRI studies, and not about how engrams might actually work.

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  • $\begingroup$ It's possible no one has measured accurately yet, but a more likely explanation is that it varies. I would assume that different memories take up a different amount of space - I have many detailed memories of my wedding day, for example, but not so many of the soccer game my child played in a month ago - it was very wet, that's all I remember :). So, it would make sense that, since the wedding memories are much more detailed, and there are many more of them, more neurons would be assigned to hold them. $\endgroup$
    – MattDMo
    Oct 18, 2016 at 15:37
  • $\begingroup$ I understand that there probably isn't a standard fixed size, though there probably are specific figures for the studies in question, but for some reason that is not published. I'm just looking for an order of magnitude to go with "sparse populations" and "small clusters". Is it 10, 100, 1000, whole fMRI voxels (100K-1M, which I doubt), etc.? IOW, how finely can implanted electrodes read and stimulate neurons? $\endgroup$ Oct 18, 2016 at 16:59

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edit: More directly answering the initial question, thank you, I misread what you wondered and was mislead a bit by a previous comment and your response to that comment.

In these experiments, they are using optical, not electrical techniques. Therefore it is a bit difficult to estimate exactly the number of cells activated directly, because light will scatter in the tissue but also fall off with distance. Based on the density of labeled and affected cells (to be stimulated, the cell has to be both a) labeled by a virus injection, and b) active in the engram) pictured in the second link you included, it seems like no more than a few to a couple dozen cells would have been activated directly.

In your comment, you said "IOW, how finely can implanted electrodes read and stimulate neurons?" - this is a different question. Implanted electrodes can read from and stimulate single neurons, or populations, depending on the electrode and experiment. It is difficult to target particular neurons with electrodes without an additional optical technique.

In the experiments you reference, optogenetic tools are used to selectively label cells that were active earlier in an experiment, and then reactivate those same cells with light. These sorts of experiments have only become possible recently with the development of those tools.

(original answer below)

Standard answer of biology applies here: "it varies", probably by species, type of memory, brain structure, etc.

But, to give you some ideas, one area that has been studied a lot in this field is the dentate gyrus of the hippocampus (the second and third links you sent, for example). One paper showed that a given memory activated something like 2-4% of the cells in that structure in a mouse http://www.sciencedirect.com/science/article/pii/S0166432811006462 with something like 1,000,000 dentate gyrus cells total in a mouse. So, that's a lot of cells, but those cells might be doing something special (pattern separation), so maybe it isn't right to think of them as the "engram" itself, or maybe we should be counting them PLUS all the cells activated in CA1, PLUS all the cells activated in cortex, etc. Whatever the case, one thing that is clear is that cells are involved in many many different engrams - if you are familiar with pop neuroscience you might recall the excitement about "grandmother cells" and "Jennifer Aniston" cells from a few years back. That's almost certainly not how engrams work, but that out of the subset of neurons and stimuli they examined, there was only limited overlap in those cases.

For fMRI studies, it's pretty hard to get a handle on the number of cells involved, but it isn't really possible to measure from "small clusters of cells" in fMRI on the same scale as in other measurement techniques. What is going to be more important for the fMRI decoding studies is "variation within a brain region" where the total number of neurons is many many millions, but the exact number involved in any one engram can't be measured with current technology.

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  • $\begingroup$ Thanks @Bryan, but this does not address my question. I am not asking about fMRI images -- voxel cell counts vary but are well-known (for example -- link). I am asking about the reverse problem, stimulating cells directly and observing behavioral results. How many cells are stimulated in such experiments -- just roughly? So it's just about the experimental procedures, not about how big engrams are or how they are structured (which I agree is a tough question). $\endgroup$ Oct 19, 2016 at 14:27
  • $\begingroup$ BTW, I am also interested in how many neurons are typically observed in experiments with implanted receptors. Again, this is just a question about experimental procedures, and not abut fMRI, but electrode implants in animals (and occasionally in humans as adjunct to medical procedures). $\endgroup$ Oct 19, 2016 at 14:46
  • $\begingroup$ Hi David, hope the edits help a bit. To add more to your comment here, with a single electrode, one can either record action potentials/spikes from a single neuron, or a population of dozens (but not easily discriminate them from each other), or record "field potentials" which correspond to membrane currents in hundreds to thousands of cells (this would be like a "very local EEG").Electrodes with multiple recording sites (often "tetrodes") can record from a few cells at once. Many implants especially in larger animals may have dozens of electrodes. $\endgroup$
    – Bryan Krause
    Oct 20, 2016 at 18:28
  • $\begingroup$ yes that helps a lot -- thanks, and sorry for my sloppy wording and my neglect/ignorance of the role of optogenetics. And that's my clue -- searching it turns up this SciAm article by Diessseroth -- link which gives me the impression that it can stimulate a single neuron under some circumstances. But the figure you give -- up to a couple dozen -- is what I need. So you get the bonus. $\endgroup$ Oct 21, 2016 at 0:56
  • $\begingroup$ Yep; if you either a) Shine light on only a single cell (most likely using 2-photon techniques or some other new tricks people are starting to use), or b) Express the gene in only a single cell in the light path, only that one cell would be affected. In the experiments you referenced, they shine light out of a 200um fiber optic cable placed into the brain area of interest. link has some information on how you can expect the light to travel out of the fiber and into brain tissue. $\endgroup$
    – Bryan Krause
    Oct 21, 2016 at 14:56

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