Weekly Brain Update: Working Memory

In an effort to bring more neuroscience to the Knit with your Brain blog, I begin this week with a new feature: Weekly Brain Update.  Each week the Society for Neuroscience publishes an issue of the Journal of Neuroscience.  This is a premiere journal with a broad range of neuroscience articles, including ones that are focused on cellular and molecular mechanisms, as well as ones that describe the neurocircuitry of complex human behaviors.  My plan is to choose an article from each issue and describe to you how the research relates to knitting.  My real goal is to motivate myself to read the journal every week; a secondary benefit will be to increase the neuroscience content of this blog.

A 16-stitch repeat that requires a hard working memory

One article from the June 26 issue has especially caught my attention.  It is about working memory and the brain mechanisms that allow us to hold information in our minds long enough to make links between events.  As a knitter, you might think about the process by which you learned the knit stitch, the sequence of events that had to happen in a particular order to form one stitch after another.  By the time you get to the step of transferring the completed stitch from the left to right needle, you needed to remember what was the first step from several seconds before.  After some practice, the sequence gets unified, and you don’t even think of the knit stitch as a series of steps anymore.  Working memory is the process of keeping the relevant information at the conscious level for a short time (it is also called short-term memory by some) so that long-lasting memories can be established by linking events together. 

The brain area that many believe makes working memory possible is the medial portion of the prefrontal cortex.  It resides in the front of the brain:  if you hold your pointer fingers alongside your nose, right up against your face pointing straight up, you’ll be pointing to the medial prefrontal cortex.  Someone who has trouble staying focused on a project might be experiencing some disruption in this brain area, which has been proposed as a mechanism for attention deficit/hyperactivity disorder.  Stress can disrupt this area, leading to a range of consequences that occur when the stress is severe or chronic.  

So you can see why it is interesting to find an article about the mechanism by which the prefrontal cortex contributes to working memory.  What turns out to be even more interesting about this article is that the researchers have used the most amazing new neuroscience tool: optogenetics!  Before this technique was developed the only way to manipulate a circuit in the brain was to inhibit or excite neurons near the circuit, or to alter the function of a single neuron, which provided very limited information about the whole circuit.  These old methods were also very slow compared to the processing speed of our amazing neurons.  With optogenetics it is possible to alter a very specific population of neurons for a very short time without affecting their normal function.  The neurons are altered by injecting a virus with a DNA sequence for a light-sensitive protein into a brain area.  Only a specific population of neurons will take up the DNA, depending on how it is tagged with a molecule that only that population of neurons uses (this is where my understanding of optogenetics is weakest).  Later, when the researchers want to alter the function of those neurons, they shine a laser nearby, which causes a reaction in the light-sensitive protein and either excites or shuts down those neurons.  If you want to know more about this technique, I highly recommend the TED talk by Ed Boyden: A Light Switch for Neurons.  I don’t think Dr. Boyden is at all confused about optogenetics!

Now, back to this week’s article.  Researchers at the University of Wisconsin-Milwaukee examined the role of the medial prefrontal cortex in forming a memory of an unpleasant event in rats.  Rats show overt signs of fear that we can see easily, in the form of freezing.  The rat remains very still for a period of seconds, sometimes minutes, allowing it to avoid detection in dangerous situations.  The researchers can easily control how dangerous a situation is to the rat, by pairing a sound with a brief foot shock. The shock doesn’t hurt the rat, but it is noticeable and not pleasant, so the rat pays close attention to the context and anything unique in the context (like the sound) in which this annoying event has occurred.  The greater the number of pairings between a noticeable sound and a foot shock, the more dangerous the sound will seem to the rat.   In that context or when hearing that sound, to the extent that the rat remembers, it will freeze for a period of time, depending on the magnitude of the perceived danger.

For the rat to benefit from this ability to sense when dangerous events are likely, it would need to link specific aspects of the situation that occurred close in time to the unpleasant event.  This can be examined by researchers who let some time elapse between the presentation of the sound and the foot shock.  This is a challenge for the brain!  Link an event that happened before to one that is happening later, when the neural trace of the early event would be gone.  Enter the medial prefrontal cortex, which is thought to somehow keep the information going when its source is no longer providing it.  Gilmartin, Miyawaki, Helmstetter, and Diba (2013, J. Neurosci, 33(26): 10910-10914) have provided evidence that the medial prefrontal cortex actually does this job.  They injected the medial prefrontal cortex of rats (which were anesthetized and positioned in a special frame that allowed the researchers to target the brain area accurately) with a virus that would deliver ArchT to the neurons there.  Then they implanted a tiny laser fiber just above where this light-sensitive protein was delivered.  They waited about 2 weeks for the rats to recover from surgery and when the light fibers were turned on, the neurons nearby shut down.  Their experiment was to turn off the neurons during the time that elapsed between the sound and foot shock, essentially removing the ability of the medial prefrontal cortex to keeo the trace in working memory.  They had a bunch of control groups in which the light was on at different times.  Then on the next day the rats were tested for the strength of their memory.  The rats that had the full function of their prefrontal cortex remembered both the context and the sound as scary.  However, if the prefrontal cortex was taken offline during the interval between the sound and the shock, the rats did not remember that the sound was scary.  This effect was very specific to the link between the sound and foot shock; the rats still showed fear in the context by itself.  The optogenetic technique allowed the researchers to turn off the brain area for a very short time,  a mere 20 seconds, which provided the evidence that was lacking to give the prefrontal cortex full credit for its working memory function. 

This would not be fun to do if we had to constantly consult the pattern.  Luckily our working memory keeps track of where we are in the pattern as each repeat is completed.

What would happen to our ability to learn the knit stitch if the medial prefrontal cortex was offline between “insert right needle into front loop of stitch on left needle” and “transfer newly formed stitch to right needle”?  We’d have to keep looking up the intermediate steps of “wrap yarn around the back of the right needle” and “draw loop on right needle through the loop on left needle” and the sequence would not get unified into a single event, the knit stitch.  We could tax the medial prefrontal cortex even more by trying to learn a lace or fair isle pattern repeat.  Next time you accomplish those amazing feats, consider thanking your medial prefrontal cortex!