Yes, that's more or less what I thought. A point of curiosity, though; if an unwanted population of cells is affected in addition to the population you aim at, how "contaminated" can a sample be, in order for a memory experiment to still be viable? Also, the engineer in me sort-of sees potential for "cleaning up" the contamination in the course of experiment. Rather, if you know which cell populations are affected, can you filter the signal from the "wrong" cells out of your sample?
You got me there, I have no idea.
I'm guessing that it's not the case that there's absolutely no contamination.
However, when compared to the pharmacological approach, in which you basically inject a drug into the desired area of the brain, it will act on many, many cells in that region, even ones that wouldn't have been recruited anyway. Even so, you can still see behavioural effects that indicate more or less what is likely happening. Problem is there are compensatory netowrks that also come into play, but I won't ramble on about that...
So, in comparison, optogenetics and even chemogenetics (DREADDs - you might like that name
) are far "cleaner" than the pharmacological approach.
Pharmacology is what I have to work with, but I dream of an opportunity to possibly spend some time in a lab with money to spare and has the whole optogenetic toolkit at their disposal.
Ah! Am I understanding correctly, that this means that there actual physiological differences in cells which were recently "written to," as compared to those cells around them, which were not? It makes sense, but I must admit I've never thought about it that way. It's absolutely fascinating that we, lowly humans, over such a historically miniscule period of time, actually managed to not only discover those differences, but also use them for experimental purposes. I mean, there is a whole mess of sciences at play here, all interconnected and co-dependent.
Yes, there are loads of physiological differences between neurons that are activated, and at different time points too. For instance, the Early Immediate Genes I mentioned earlier result in proteins that are expressed by only the neurons that were recruited. We can see those too, using immunohistology techniques. One such gene is FOS, which encodes for the c-fos protein.
This is a section of a rat hippocampus (proportionally larger than ours).
The red/orangy cells are ones which were last recruited during a behavioural task, which express the early immediate gene protein, c-fos. The green dots are neurons and blue dots are the nuclei of neurons and glial cells.
I could stare at that image all day.
This is another thing I never thought about. You see on illustrations of stuff like dopamine or serotonin uptake, that they always draw a space between the cells, in which the chemicals "fly" between receptors. I always assumed that it was purely for illustrative convenience, and that the neural "wires" were continuous, if made of a myriad individual strands.
Funnily enough, that was the debate/argument that Golgi and Ramón y Cajal ("father of neuroscience") had at the turn of the 20th century. Golgi believed that everything was continuous while Cajal said that cells were discrete units, not continuously joined. Cajal was right, but both were awarded the Nobel prize.
https://en.wikipedia.org/wiki/Reticular_theory 
Ah, I had to list the distinction between two types of synapse in the entry exam for my master's...let's see if I can still remember:
There are two types of synapses,
electrical, which are in physical contact with eachother and there are no neurotransmitters, and
chemical, in which there is a cleft between them and neurotransmitters are necessary to get the signal across. In invertebrates, synapses are mostly electrical whereas in vertebrates they're mostly chemical. Electrical synapses are bidirectional whereas chemical synapses go only in one direction, from the presynaptic neuron to the postsynaptic neuron, though there are the so-called 'atypical neurotransmitters', such as endocannabinoids that go in the inverse direction (yes, our systems produce cannabinoids
).
What else...
Electrical synapses are faster than chemical ones. But if they're faster, then why have chemical synapses in the first place, and why do 'more evolved' animals such as vertebrates have more chemical synapses? One answer is that chemical synapses are regulated. They're more complex, but there are more 'steps' along the way that can be inhibited, facilitated or modulated, resulting in a larger behavioural repertoire.
Makes an person wonder, is this at least partly the reason for our "sensory lag?" As in, from light hits the retina and until the brain has an image to process, for example? I mean, light, it moves at the speed of light. Chemical reactions - not so much, and transmission of chemicals may be slower still.
See above.
The difference in speed between the two types of synapses isn't so great, though. Since most neurotransmitters are small molecules that can diffuse rapidly and the cleft is tiny, there is only a small delay.
Oh, I can see how it takes a lot of people a lot of hours (not to mention all those thousands of heroic ratties, who show up and do their part every day, in the name of their God, in order to further human understanding of the natural world) to figure this stuff out. I mean, I'm pretty sure that most of the questions I ask are barely above high school level, because that's where my understanding of this topic is, but it's damned interesting. You have a really cool job!
Yes, it's a cool job, but can be damned frustrating, though! That's science for ya.
As for the ratties, yes, they are heroic. One of my labmates even added them in the acknowledgement part of his thesis. I thought that was awesome.
While animal experimentation is a controversial topic (my family, for instance, does not approve), all experiments have to be approved by an ethics committee made up of people from many backgrounds before they can be done. You have to be rigorous in your justification for using animals before you can use them. That's why scientists have to be 'salespeople' as well, you have to 'sell' your idea to others all the time.
I like your picture analogy. The one I thought up, was more along the lines of oral tradition of storytelling - with each passing generation, the story changes a little, without quite losing what it used to be. It's a bit like... Evolution, actually. Every child is of the same species as its parents, and yet given enough generations, the species are similar, but completely different. It even works, in a manner, in distinguishing stuff like generalised memories (a human is a hominid is a mammal is a vertebrate). I likes my analogy and hereby claims copyright! 
(Yes, yes, I know, but don't tell me that somebody already made it a hundred years ago. Is MY epiphany now)
So... It's kind of like different parts of the brain are responsible for discrete levels of intricacy of a given memory? Yes, this right here, is where a lot of very cool answers lie. It would be really interesting to figure out if a memory, once "written," is static to that general cluster of neurons, or if it can indeed be "transferred" from one to the other. What quality, or "resolution," if you will, would such a memory hold, I wonder... Actually, given what I've read about the experiments being done in this field in this very conversation, I wonder if transplanting a memory, however imperfectly, is not a doable experiment? Has it been done, or at the very least proposed, perchance?
Memories tend to become more generalised when they become more dependent on cortical structures. They lose detail, and become more 'semantic'. This means that they do lose some precision, and some researchers have proposed it is a form of forgetting, but I think not. Generalisation is not the same as forgetting.
Implanting memories?
I don't think it's theoretically possible to 100% transfer a memory because everyone's brain in different in their connections, memories are coloured by perception as well, and attention...I don't know. I'll have to look into that. It would be cool if it were possible, though!
Oh, this, I'm definitely reading up on. I expect I'll have to bounce some questions off you and clear up some misunderstandings, what with my bias towards seeing the world through a pair of engineer-glasses.
