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Capstone project proposal template cheap write for me qld electrical capstone test need someone to write dissertation on government asap well basically in the definition that Lynn mentioned in which a memory is stored as a record of an experience in the brain so the to me the the fundamental question is what is the nature of that record I mean what is the biological basis of memory storage and the thing to realize is that no one's had any idea at all I mean it goes back to Plato writing about wax writing on wax tablets as the metaphor for memory and so a hundred years ago when scientists discovered by looking microscopes that there in neurons and that there are connections between the neurons called synapses people speculated that the changes in the strength of those connections would be the involved in the mechanism of the memory but no one had any idea what the persistence mechanism was so so just the give example a year from now the people in the audience may have a connection between Maurice Chevalier and Danny Kaye the comedian because this is his theater and five people sitting on these cool red chairs and so that the memory so they may know maurice chevalier and that was probably if they're thinking that that's probably maybe a thousand to ten thousand neurons firing at once in a network and that network had never been connected with Danny Kaye and that network had never been connected with five people talking about memory for an hour and a half but a year from now the people in the audience might remember that and that's because some change happened in that synaptic connections and so basically that was the big discovery that my lab and my collaborators me almost precisely five years ago which was we discovered the first molecular mechanism for that memory storage and what was shocking to the pretty much the entire neuroscience community was that it was a very specific molecule and the nature of this molecule was an enzyme so hardly anyone expected that and what an enzyme is basically it's a it's a type of protein that catalyzes that helps that promotes a chemical reaction so what we found was that in the brain when a connection between maurice chevalier and Danny Kaye has been made those synapses that were already there now started making this molecule which is called protein kinase mz8 or PKM Zaidan that was persistently doing a chemical reaction so that was our hypothesis so we tested that hypothesis by giving to the an animal experimental animal rat into their hippocampus the part of the brain that's storing for for animals non-human animals storing spatial information and we can talk about that later on so we basically taught an animal to avoid an area of space and then waited a day and then injected into the hippocampus of the animal this drug which is called zip for zeta inhibitory peptide we injected this drug zip and for the first time anyone has ever shown we're able to erase that memory so is this we have video of this right we have video yep so this is a naive animal and we put the rat into the apparatus that's a little LED light that just so we can see it now the shock is not on see that's the gray zone that little Pizza wedge that's where the shop will be in a few minutes so right now we put a naive animal in it's spending most of its time on the outside of the apparatus maybe looking through the walls which are clear plastic now we turn the shock on for 10 minutes and we turn it it off for 10 minutes put it in its home cage and after eight of these 10 minute episodes the animal has learned to avoid the shock zone so notice that the information that's on the floor of the apparatus is useless if the act the rat has to look out into the room and that really engages the hippocampus so now a day later we put the rat back in and we inject saltwater saline as the control and we're testing with the shock off these injections are into the hippocampus right yes hippocampus on both sides so you see if the rat avoids shock is off but it just avoided that area now we take another set of rats trained it exactly the same way waited a day and injected zip no evidence of the memory having been there in fact if you take a picture of the exactly the same rat when it was in its naive state before it was trained and after its memory had been erased there's absolutely no difference in this behavior so we can turn that off so is this scalable to humans in any way or this does have clinical applications that we would care about I yeah but I erased okay so wife's memory of various nevermind carry on well right now it would have erased all information all and remain your wife's prank that we didn't call it Stepford drugs so the goal eventually is to understand how this molecule is storing memory and understanding it in real detail so that we can harness the power of this ability to erase the memory so let me just say people have gone out since these five years many of the different types in fact all of the different types except for Prime all of the different types of memories from Pavlovian conditioning to spatial memories to fear conditioning they've all been erased by this drug and now three other different versions of different ways of inhibiting PKM zeta so the evidence is pretty strong that this is a fundamental mechanism for the storage of memory in the brain so you can answer your question about clinical this is a discussion here about memory but the brain doesn't know that the brain is using information storage for all sorts of things that were not even calling memory so for example there's a disease called chronic neuropathic pain which is essentially the memory of a painful incident that's happened that setup in the spinal cord and in some unconscious areas of the of the brain and other researchers not not from my lab have used it to erase those memories in rats in rat models of chronic neuropathic pain so I think that's the first clinical application and late in the last few months we've shown we can actually enhance old memories by putting more PKM zeta in but again using a virus so we can't really probably can't do that in people but the goal of getting specific memory erasing would be to harness the potency of PKM zeta and it's inhibition and that process of reconsolidation that you mentioned so Oh before we do there's one more thing that I want to show if I could basically by identifying the molecule that's essential for storage we can now actually see a memory being stored in the brain so if I can just show that what we call the rainbow slide so basically this was that Saline controlled animal we're looking at PKM zeta the more yellow and the more red it is the more peaky MZ is in there in the brain so this is that hippocampus little structure that we talked about so that's an animal that was naive and not trained and here's an animal a day after its training and all that yellow dots in there are the PKM zeta molecules that have been formed and maintained for a day scientists have actually gone out to at least a month and we see that increase and in that lat my last slide we can now look at real detail this is a neuron that we've injected with a dye and we could see that's the cell body and that's the dendrites and these are the the synaptic connections are on these little mushroom like things coming off of the dendritic shaft and these are called spines so we can actually for the first time say how many synapses are actually involved in the encoding of a memory here we see one right here it's yellow here they're these other spines don't have P gamma Zeta so we're actually counting the synapses in order to say how many synapses are actually storing a long term memory no no one had any idea or any way of doing something like that do my best research topics of 2017 Law Center, Central Islip.