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Jan
14th
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What are memories made of?


“There appears to be no single memory store, but instead a diverse taxonomy of memory systems, each with its own special circuitry evolved to package and retrieve that type of memory. Memories are not static entities; over time they shift and migrate between different territories of the brain.

At the top of the taxonomical tree, a split occurs between declarative and non-declarative memories. Declarative memories are those you can state as true or false, such as remembering whether you rode a bicycle to work. Non-declarative memories are those that cannot be described as true or false, such as knowing how to ride a bicycle. A central hub in the declarative memory system is a brain region called the hippocampus. This undulating, twisted structure gets its name from its resemblance to a sea horse. Destruction of the hippocampus, through injury, neurosurgery or the ravages of Alzheimer’s disease, can result in an amnesia so severe that no events experienced after the damage can be remembered. (…)

A popular view is that during sleep your hippocampus “broadcasts” its recently captured memories to the neocortex, which updates your long-term store of past experience and knowledge. Eventually the neocortex is sufficient to support recall without relying on the hippocampus. However, there is evidence that if you need to vividly picture a scene in your mind, this appears to require the hippocampus, no matter how old the memory. We have recently discovered that the hippocampus is not only needed to reimagine the past, but also to imagine the future.

Pattern completion

Studying patients has taught us where memories might be stored, but not what physically constitutes a memory. The answer lies in the multitude of tiny modifiable connections between neuronal cells, the information-processing units of the brain. These cells, with their wispy tree-like protrusions, hang like stars in miniature galaxies and pulse with electrical charge. Thus, your memories are patterns inscribed in the connections between the millions of neurons in your brain. Each memory has its unique pattern of activity, logged in the vast cellular network every time a memory is formed.

It is thought that during recall of past events the original activity pattern in the hippocampus is re-established via a process that is known as “pattern completion”. During this process, the initial activity of the cells is incoherent, but via repeated reactivation the activity pattern is pieced together until the original pattern is complete. Memory retention is helped by the presence of two important molecules in our brain: dopamine and acetylcholine. Both help the neurons improve their ability to lay down memories in their connections. Sometimes, however, the system fails, leaving us unable to bring elements of the past to mind.

Of all the things we need to remember, one of the most essential is where we are. Becoming lost is debilitating and potentially terrifying. Within the hippocampus, and neighbouring brain structures, neurons exist that allow us to map space and find our way through it.Place cells" provide an internal map of space; "head-direction cell" signal the direction we are facing, similar to an internal compass; and "grid cells" chart out space in a manner akin to latitude and longitude.

For licensed London taxi drivers, it appears that navigating the labyrinth of London’s streets on a daily basis causes the density of grey matter in their posterior hippocampus to increase. Thus, the physical structure of your brain is malleable, depending on what you learn.

With impressive technical advances such as optogenetics, in which light beams excite or silence targeted groups of neurons, scientists are beginning to control memories at an unprecedented level.”

Hugo Spiers is a neuroscientist and lecturer at the institute of behavioural neuroscience at University College London, What are memories made of?, The Guardian, Jan 14, 2012 (Illustration: Polly Becker)

How and why memories change

"Since the time of the ancient Greeks, people have imagined memories to be a stable form of information that persists reliably. The metaphors for this persistence have changed over time—Plato compared our recollections to impressions in a wax tablet, and the idea of a biological hard drive is popular today—but the basic model has not. Once a memory is formed, we assume that it will stay the same. This, in fact, is why we trust our recollections. They feel like indelible portraits of the past.

None of this is true. In the past decade, scientists have come to realize that our memories are not inert packets of data and they don’t remain constant. Even though every memory feels like an honest representation, that sense of authenticity is the biggest lie of all. (…)

New research is showing that every time we recall an event, the structure of that memory in the brain is altered in light of the present moment, warped by our current feelings and knowledge. (…)

This new model of memory isn’t just a theory—neuroscientists actually have a molecular explanation of how and why memories change. In fact, their definition of memory has broadened to encompass not only the cliché cinematic scenes from childhood but also the persisting mental loops of illnesses like PTSD and addiction—and even pain disorders like neuropathy. Unlike most brain research, the field of memory has actually developed simpler explanations. Whenever the brain wants to retain something, it relies on just a handful of chemicals. Even more startling, an equally small family of compounds could turn out to be a universal eraser of history, a pill that we could take whenever we wanted to forget anything. (…)

How memory is formed

Every memory begins as a changed set of connections among cells in the brain. If you happen to remember this moment—the content of this sentence—it’s because a network of neurons has been altered, woven more tightly together within a vast electrical fabric. This linkage is literal: For a memory to exist, these scattered cells must become more sensitive to the activity of the others, so that if one cell fires, the rest of the circuit lights up as well.

Scientists refer to this process as long-term potentiation, and it involves an intricate cascade of gene activations and protein synthesis that makes it easier for these neurons to pass along their electrical excitement. Sometimes this requires the addition of new receptors at the dendritic end of a neuron, or an increase in the release of the chemical neurotransmitters that nerve cells use to communicate. Neurons will actually sprout new ion channels along their length, allowing them to generate more voltage. Collectively this creation of long-term potentiation is called the consolidation phase, when the circuit of cells representing a memory is first linked together. Regardless of the molecular details, it’s clear that even minor memories require major work. The past has to be wired into your hardware. (…)

What happens after a memory is formed, when we attempt to access it?

The secret was the timing: If new proteins couldn’t be created during the act of remembering, then the original memory ceased to exist. The erasure was also exceedingly specific. (…) They forgot only what they’d been forced to remember while under the influence of the protein inhibitor.

The disappearance of the fear memory suggested that every time we think about the past we are delicately transforming its cellular representation in the brain, changing its underlying neural circuitry. It was a stunning discovery: Memories are not formed and then pristinely maintained, as neuroscientists thought; they are formed and then rebuilt every time they’re accessed. “The brain isn’t interested in having a perfect set of memories about the past,” LeDoux says. “Instead, memory comes with a natural updating mechanism, which is how we make sure that the information taking up valuable space inside our head is still useful. That might make our memories less accurate, but it probably also makes them more relevant to the future.” (…)

[Donald] Lewis had discovered what came to be called memory reconsolidation, the brain’s practice of re-creating memories over and over again. (…)

The science of reconsolidation suggests that the memory is less stable and trustworthy than it appears. Whenever I remember the party, I re-create the memory and alter its map of neural connections. Some details are reinforcedmy current hunger makes me focus on the ice cream—while others get erased, like the face of a friend whose name I can no longer conjure. The memory is less like a movie, a permanent emulsion of chemicals on celluloid, and more like a play—subtly different each time it’s performed. In my brain, a network of cells is constantly being reconsolidated, rewritten, remade. That two-letter prefix changes everything. (…)

Once you start questioning the reality of memory, things fall apart pretty quickly. So many of our assumptions about the human mind—what it is, why it breaks, and how it can be healed—are rooted in a mistaken belief about how experience is stored in the brain. (According to a recent survey, 63 percent of Americans believe that human memory “works like a video camera, accurately recording the events we see and hear so that we can review and inspect them later.”) We want the past to persist, because the past gives us permanence. It tells us who we are and where we belong. But what if your most cherished recollections are also the most ephemeral thing in your head? (…)

Reconsolidation provides a mechanistic explanation for these errors. It’s why eyewitness testimony shouldn’t be trusted (even though it’s central to our justice system), why every memoir should be classified as fiction, and why it’s so disturbingly easy to implant false recollections. (The psychologist Elizabeth Loftus has repeatedly demonstrated that nearly a third of subjects can be tricked into claiming a made-up memory as their own. It takes only a single exposure to a new fiction for it to be reconsolidated as fact.) (…)

When we experience a traumatic event, it gets remembered in two separate ways. The first memory is the event itself, that cinematic scene we can replay at will. The second memory, however, consists entirely of the emotion, the negative feelings triggered by what happened. Every memory is actually kept in many different parts of the brain. Memories of negative emotions, for instance, are stored in the amygdala, an almond-shaped area in the center of the brain. (Patients who have suffered damage to the amygdala are incapable of remembering fear.) By contrast, all the relevant details that comprise the scene are kept in various sensory areas—visual elements in the visual cortex, auditory elements in the auditory cortex, and so on. That filing system means that different aspects can be influenced independently by reconsolidation.

The larger lesson is that because our memories are formed by the act of remembering them, controlling the conditions under which they are recalled can actually change their content. (…)

The chemistry of the brain is in constant flux, with the typical neural protein lasting anywhere from two weeks to a few months before it breaks down or gets reabsorbed. How then do some of our memories seem to last forever? It’s as if they are sturdier than the mind itself. Scientists have narrowed down the list of molecules that seem essential to the creation of long-term memory—sea slugs and mice without these compounds are total amnesiacs—but until recently nobody knew how they worked. (…)

A form of protein kinase C called PKMzeta hangs around synapses, the junctions where neurons connect, for an unusually long time. (…) What does PKMzeta do? The molecule’s crucial trick is that it increases the density of a particular type of sensor called an AMPA receptor on the outside of a neuron. It’s an ion channel, a gateway to the interior of a cell that, when opened, makes it easier for adjacent cells to excite one another. (While neurons are normally shy strangers, struggling to interact, PKMzeta turns them into intimate friends, happy to exchange all sorts of incidental information.) This process requires constant upkeep—every long-term memory is always on the verge of vanishing. As a result, even a brief interruption of PKMzeta activity can dismantle the function of a steadfast circuit. (…)

Because of the compartmentalization of memory in the brain—the storage of different aspects of a memory in different areas—the careful application of PKMzeta synthesis inhibitors and other chemicals that interfere with reconsolidation should allow scientists to selectively delete aspects of a memory. (…)

The astonishing power of PKMzeta forces us to redefine human memory. While we typically think of memories as those facts and events from the past that stick in the brain, Sacktor’s research suggests that memory is actually much bigger and stranger than that. (…)

Being able to control memory doesn’t simply give us admin access to our brains. It gives us the power to shape nearly every aspect of our lives. There’s something terrifying about this. Long ago, humans accepted the uncontrollable nature of memory; we can’t choose what to remember or forget. But now it appears that we’ll soon gain the ability to alter our sense of the past. (…)

The fact is we already tweak our memories—we just do it badly. Reconsolidation constantly alters our recollections, as we rehearse nostalgias and suppress pain. We repeat stories until they’re stale, rewrite history in favor of the winners, and tamp down our sorrows with whiskey. “Once people realize how memory actually works, a lot of these beliefs that memory shouldn’t be changed will seem a little ridiculous,” Nader says. “Anything can change memory. This technology isn’t new. It’s just a better version of an existing biological process.” (…)

Jonah Lehrer, American author and journalist, The Forgetting Pill Erases Painful Memories Forever, Wired Magazine, Feb 17, 2012. (Third illustration: Dwight Eschliman)

"You could double the number of synaptic connections in a very simple neurocircuit as a result of experience and learning. The reason for that was that long-term memory alters the expression of genes in nerve cells, which is the cause of the growth of new synaptic connections. When you see that at the cellular level, you realize that the brain can change because of experience. It gives you a different feeling about how nature and nurture interact. They are not separate processes.”

Eric R. Kandel, American neuropsychiatrist, Nobel Prize laureate, A Quest to Understand How Memory Works, NYT, March 5, 2012

Prof. Eric Kandel: We Are What We Remember - Memory and Biology

Eric R. Kandel, American neuropsychiatrist, Nobel Prize laureate, We Are What We Remember: Memory and Biology, FORA.tv, Prohansky Auditorium New York, NY, Mar 28.2011

See also:

☞ Eric R. Kandel, The Biology of Memory: A Forty-Year Perspective (pdf), Department of Neuroscience, Columbia University, New York, 2009
☞ Eric R. Kandel, A Biological Basis for the Unconscious?, Eric Kandel: “I want to know where the id, the ego, and the super-ego are located in the brain” | Big Think video Apr 1, 2012.
Memory tag on Lapidarium notes