Saturday, June 11, 2016

MIT Discovers the Location of Memories: Individual Neurons

A transgenic mouse hippocampus

I have long understood that the principal task of a neuron had to be setting up and encoding access to a memory. We still do not show how it is actually coded.  It is there where we have to speculate.  My own preference is to simply link directly to the time sheet of the memory and that may well actually happen.  However memory loss and malleability tends to suggest otherwise or at least the existence of two levels of memory retentionWe obviously rely on the weaker version. 


We at least have a networking system and some sort of search facility to figure out..

MIT discovers the location of memories: Individual neurons

By Sebastian Anthony on March 23, 2012 at 8:35 am

Update 12/2/15: We’ve now followed up on this story: The more we learn about memory, the weirder it gets. The original continues below.

MIT researchers have shown, for the first time ever, that memories are stored in specific brain cells. By triggering a small cluster of neurons, the researchers were able to force the subject to recall a specific memory. By removing these neurons, the subject would lose that memory.

As you can imagine, the trick here is activating individual neurons, which are incredibly small and not really the kind of thing you can attach electrodes to. To do this, the researchers used optogenetics, a bleeding edge sphere of science that involves the genetic manipulation of cells so that they’re sensitive to light. These modified cells are then triggered using lasers; you drill a hole through the subject’s skull and point the laser at a small cluster of neurons.

Now, just to temper your excitement, we should note that MIT’s subjects in this case are mice — but it’s very, very likely that the human brain functions in the same way. To perform this experiment, though, MIT had to breed genetically engineered mice with optogenetic neurons — and we’re a long, long way off breeding humans with optogenetic brains.

In the experiment, MIT gave mice an electric shock to create a fear memory in the hippocampus region of the brain (pictured above) — and then later, using laser light, activated the neurons where the memory was stored. The mice “quickly entered a defensive, immobile crouch,” strongly suggesting the fear memory was being recalled.

The main significance here is that we finally have proof that memories (engrams, in neuropsychology speak) are physical rather than conceptual. We now know that, as in Eternal Sunshine of the Spotless Mind, specific memories could be erased. It also gives us further insight into degenerative diseases and psychiatric disorders, which are mostly caused by the (faulty) interaction of neurons. “The more we know about the moving pieces that make up our brains,” says Steve Ramirez, co-author of the paper. “The better equipped we are to figure out what happens when brain pieces break down.”

Bear in mind, too, that this research follows on from MIT’s discovery last year of Npas4, the gene that controls the formation of memories; without Npas4, you cannot remember anything. MIT has successfully bred mice without the Npas4 gene.

The question now, though, is how memories are actually encoded — can we programmatically create new memories and thus learn entire subjects by inserting a laser into our brain? We know that a cluster of neurons firing can trigger the memory of your first kiss — but why? How can 100 (or 100,000) neurons, firing in a specific order, conjure up a beautifully detailed image of an elephant? We’ve already worked out how images are encoded by the optic nerve, so hopefully MIT isn’t too far away from finding out.

The more we learn about memory, the weirder it gets 

By Graham Templeton on December 2, 2015 at 2:11 pm 


For much of the history of brain science, the word “engram” has been a bit of a catch-all term, referring to the hypothetical physical incarnation of memory. If this turned out to be a storm of electrical activity, then that’s what the engram would be; if it turned out that networks of physical neurons were the home of specific memories, then an engram was that, instead.

Lately, though, the word has gotten a lot more specific. We now have the term “memory neurons” to refer to the nerve cells of the hippocampus, which seem to play a crucial role in storing and retrieving memories. Since the original proof that at least some memory is localized to specific physical neurons just a few short years ago, understanding of the physical basis of memory has advanced at a lightning pace.

Even in the past year, scientists have made incredible strides. One amazing study may have found the molecular basis for memory formation — the seemingly harmful breakage of DNA. It turns out an enzyme from the topoisomerase family responds to new stimuli by breaking DNA, which seems to activate the transcription of as many as a dozen quick-acting genes associated with neural development. These genes are inhibited by a system of enzymes, but as the now-broken DNA folds up in response to its new situation, these inhibitory genes are blocked, and the now-uninhibited memory genes are free to go out and direct the development of the brain.

Here is a rat set up so that certain neurons will fire in response to a UV light. Though double-stranded breaks in DNA are generally thought of as being bad for the cell, topoisomerases serve an important role in the cell, breaking, unwinding, and reconnecting the double helix if it’s about to become over-wound and tie itself up into knots. Here, the large-scale conformational change associated with breaking a molecule of DNA acts as a wide-reaching promoter of transcription. By breaking a strand of DNA, a seemingly dangerous thing to do, it can quickly and efficiently activate a wide and physically scattered collection of genes. As we age, our ability to repair such damage to DNA gets less and less powerful — which could help account for the worsened ability to create new short- and long-term memories.


Speaking of long-term memories, a separate study found that the retrieval of long-term memories could one-day be assisted with technology. They showed that by blocking protein synthesis in brain cells, we can stop a mouse from remembering things that it learns — teach it the location of some food while its brain is incapable of strengthening the synaptic pathways between neurons. The mouse will reliably not remember the fact it “learned” just a few hours before but, intriguingly, the researchers could retrieve the memory by artificially causing the specific learning cells associated with the memory to fire.

The researchers say this experimental setup can help to distinguish between the methods of memory formation and memory retrieval. By stopping the mouse brain from strengthening the synaptic connections in response to new info, they seem to have made memory retrieval more difficult. However, when they cause that retrieval to happen on their own, the pattern of synaptic connections associated with that memory will still function properly. This has been interpreted as some of the first evidence showing that augmentation of synapses in these cells of the hippocampus is strongly related to memory.

Brain implants are still a bit unwieldy… Study author Tomas Ryan said, “The strengthening of engram synapses is crucial for the brain’s ability to access or retrieve those specific memories, while the connectivity pathways between engram cells allows the encoding and storage of the memory information itself.” These are much more definitive, strident statements than any scientists could have made just five years ago, or even less.

However, it’s almost certainly not that simple. This Stanford team has put forth the idea of mobile memories, in which the hippocampus does indeed store the specifics of new memories in its synaptic connections, but after a while those memories move to elsewhere in the brain. The team found that if they disrupted the hippocampus within a month or so of a new memory, the memory disappeared forever. If they disrupted it after a longer period of time, the memory seemed undisturbed — as though it no longer physically resides in those same cells.

This seems to provide a fairly stark physiological difference that could form the basis for some of the distinctions between short and long term memory — but if the study of memory has taught us anything, it’s that we can’t assume it works in a simple or reasonable way. Occam’s Razor may still apply to the physiology of memory, but when creating such a nuanced aspect of cognition as memory, perhaps it just isn’t possible to slice all that much complexity away.

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