The Memory Exchange

Have you wondered if memories last forever and are forever faithful, or are they mercurial? Is it the same for all kinds of memories? Can pleasant memories be strengthened and disturbing ones erased, and by what means? Memories are a central part of life, contributing greatly to who we believe ourselves to be, yet we find memory and recall mysterious. Neuroscience has interesting things to say about how memories are formed, strengthened, destabilized, restored and erased.

Making Memories

A memory is a combination of the objective information surrounding an event and the emotion we attach to it; emotions like joy, satisfaction, fear, anxiety, etc. A memory is also a series of biochemical and physical changes in the brain that encode and link the pieces of the memory together and store the ensemble for later recall.

When a memory is first acquired the new information is processed in stages. Short term memory refers to activity in neural circuits, for example the circuits in the hippocampus that are responsible for the first steps in encoding. These early steps are labile, lasting only seconds to minutes, have quite limited capacity and are easily distracted by competing inputs so that they are ignored for the moment. Working memory (more a concept than a defined process) also has limited capacity but functions to combine and encode the various elements of an experience (the who, what, why, color, taste, shape) as the details and links undergo the process of stabilization and consolidation. Long term memory, termed consolidation, requires the formation of new synapses, the strengthening or weakening of existing synapses and the growth of brand new physical connections. As a result, neural pathways are reinforced and the memory trace solidified by enhancing the actual anatomical connections between neurons at distributed sites in the brain. These strengthened synaptic pathways are in a real and physical sense, the memory. All of this involves the activation of specific genes and changes in the expression of specific cellular proteins in sequence. Consolidation occurs over a time course of hours, but once completed the memory is stable and available for recall, possibly for the rest of our lives. It is not too farfetched to suggest that every memory we have ever had is stored. Taking this view, what it means to forget is only a matter of the ease of recall.

Memory and Emotion

The emotional content of a memory has a critical impact on both storage and recall. Emotion selectively creates enduring memories and prioritizes them. The stronger the emotional content, the easier it is to recall a memory and this is true regardless of the valence of the emotion. This is a big clue about the neurobiology of memory.

The two elements of a memory, the objective content and the subjective emotion, involve different brain regions; the hippocampus for storage and recall, and the amygdala for attending to emotion. The two systems are closely linked. Neurons in the amygdala project to the hippocampus using the neurotransmitter norepinephrine. Both regions supply inputs to parts of the forebrain and wider cortex, as well. The distributed nature of this architecture allows a large array of influences to act on the memory process; one example being the stress hormones epinephrine and corticosterone which act on neurons in the amygdala.

About Sleep and Memory

While you sleep, your brain sorts through the memories formed during the day, selecting some for consolidation, and also linking new memories with earlier ones. There is also an indication that entirely new memories can be created out of dreams; think “vivid dreaming” for example. This is an area of intense research and an industry for psychologists. The literature on sleep, dreams and memory is thick and I am a novice, so this is just a snippet. I hope it motivates you to look deeply into sleep research on your own, it is fascinating.

Matthew Walker at Berkeley concludes that sleep both prepares the brain for learning and is essential for cementing new information into the architecture of the brain (consolidation), making it available for later recall. He says, “Think twice before pulling an all-nighter to study for your next exam: If you don’t sleep, your ability to learn new information could drop by up to 40%.” Graduation does not dilute the power of that admonition.

During sleep, the brain cycles between phases of light sleep, deep sleep, and rapid eye movement (REM) sleep. The cycles repeat about every 90 minutes. It seems to work like this: We accumulate memories moment by moment while we are awake and they come at such a rate that most are forgotten during the day. Robert Stickgold at Harvard Med., explains that this is short term memory; memory in a raw and fragile form; “…sleep seems to be a privileged time when the brain goes back through recent memories and decides both what to keep and what not to keep.”

Memories appear to become stabilized during the deep stages of sleep. After that REM, the most active stage for dreaming, seems to play a role in linking related memories together, sometimes in unexpected ways. Maybe that’s why a full night’s sleep seems to help with problem-solving; allowing new linkages to form.

Modifying Memories

Memory is strengthened when we repeat a task during the initial learning. This is obvious when acquiring a new motor skill like juggling. Memories are also strengthened on recall at a later time even in a completely different context, but this type of strengthening involves a different process than the initial consolidation. This difference is at the root of how we might set out to modify our memories.

The current thought about strengthening on recall, called reconsolidation, goes like this; retrieving a memory trace physically decouples the synapses that support the trace.  This as an obligatory step in recall. It means that on recall the memory is physically disassembled by enzymes that degrade the structural proteins that give synapses their shape and are essential for function. But the memory is not lost because recall also initiates a new round of protein synthesis to provide the molecular materials needed to reestablish the uncoupled synapses, and even strengthen the connections. There is more, as the memory is reestablished, it is integrated with the current, ongoing perceptual and emotional background so that it literally becomes a new memory with the old core but with added parts. So, the memory is refabricated between recall and reconsolidation, perhaps a little embellished and especially so if new emotional content is available to be added. Another way to say this is that during recall the memory becomes labile again and is available for strengthening, modification or erasure.  You have experienced this, I know. It is the kind of thing that makes for drama in the courtroom and lawyers know all about it.  I am sure you see the broader implications.

This all sounds a little improbable, but there is plenty of evidence to support reconsolidation through a labile period. For example, if protein synthesis is prevented by introducing an inhibitor during recall, the memory is lost. The idea is also supported, not yet proven, by detailed study of the cellular signaling pathways and gene transcription factors involved. The beauty of the thing is that it allows memories to be updated and adapted to our constantly changing experience.  Lability on recall is a conserved feature of memory systems seen in animals as diverse as sea slugs, insects, birds and mammals. The strength of the effect depends on the age of the memory, the amount of training, and the frequency and duration of recall episodes. New and strong memories, and repeated short recall sessions, are more available for modification on recall. One take away from this is that ruminating about some past bummer is a good way to insure that it will hound you forever. That is worth thinking about.

A Shout-out for Daydreaming

Daydreaming gets a bad rap that I think is totally undeserved because it is one of the great pleasures of the mind. You know and I know we spend hours daydreaming, commonly ruminating on the negative. Suppose we take the flipside and spend our daydream time reflective on the positive. The theory of memory we are exploring says that memories undergo a labile period during reconsolidation after recall. Suppose we use our will power to guide daydreaming time toward thinking about the big positives, using memory as a guide. This will strengthen those positive memories. Give it a try, but be sure to daydream about things that give you pleasure. An example; being connected to someone involves lots of daydreaming about your partner. It is part of bonding. Daydreaming about the bond will strengthen it more effectively than text messages or flowers.

Extinction of Bummer Memories

Extinction training is sometimes used in an attempt to reduce the recall of a destructive memory. The therapist asks a person to revisit an emotionally charged experience multiple times but in a setting that is completely different than the original one. The goal is to gradually weaken the emotional content. Because memories are not recalled and returned in exactly the same form, new information, provided for example by a neutral or positive environment, eventually lowers the emotional content and the effect is to suppress recall. This is a direct result of the plasticity inherent in reconsolidation. You can do this yourself, it only takes will power and a desire to quit ruminating and move on.

We know from long experience that memories with a strong emotional content are easiest to recall. Most of the time that is absolutely great and gives life its rich luster. But it is also at the heart of the problem in PTSD and childhood trauma. These are tough memories to overcome, few people have the will or the finances necessary to do the work so the success rate is not high. Suppose there was a magic pill we could take to suppress a negative memory during reconsolidation and in that way make recall difficult. As our understanding of the memory process grows, it seems certain that such a pill will come along; it might already be here. To be useful, however, it has to be specific and not cause some kind of global amnesia. That leaves stuff like ketamine and general anesthetics out of the running.

Toward a Magic Memory Pill

Propranolol is a beta- blocker with a long history in the treatment of high blood pressure and the anxiety of stage fright. It has these effects because it blocks receptors for the neurotransmitter norepinephrine and it can be taken orally with few side effects. Propranolol is finding new and surprising application in the modification of memories during reconsolidation.

Here is the cool finding, propranolol given during memory reconsolidation reduces subsequent recall of emotionally charged memories.  It appears to work like this; we know that emotions play a strong role in memory acquisition and consolidation. Under highly emotional conditions (either positive or negative), neurons in the amygdale (emotion center) are activated. These neurons send projections to the hippocampus (memory center) and regions of the forebrain (executive center) where they release norepinephrine at synapses onto cells in memory pathways. The result is that the synapses are strengthened and this is why emotionally charged memories are so vividly recalled.

Propranolol prevents this strengthening by blocking the activation of synapses in memory pathways by norepinephrine. This is a very straight forward and direct action and it effectively prevents the incorporation of emotional content into memories on reconsolidation.  For example, blocking norepinephrine synapses immediately after learning can, in some circumstances, produce retrograde amnesia. There is also evidence that synaptic plasticity at hippocampal synapses depends on modulation by norepinephrine and is blocked by propranolol. Now, imagine an extinction therapy session, but this time the client is given propranolol before being guided through a destructive memory. After a few repetitions, the memory loses its importance. That’s interesting.

There are lots of questions to ask about how propranolol works, the circumstances in which it is effective and whether the effects are long lasting. Some of the cellular and molecular mechanism of action are already known, but I think this is only the first step and that the researchers who peruse this kind of thing will come up with much improved pharmaceuticals, and it won’t take them long!