Deciphering How Memory Works

Posted on November 18, 2007
Filed Under Science |

The human brain is remarkable in its ability to remember things for short periods of time in what is referred to as working memory. A waiter who takes your order and several others at your table without pen and paper, picking out tools at a store that you are going to use for repairs, picking up groceries that have been relayed to you on your phone without pen and paper. These short periods of time in which we are called upon to remember things reflects the use of our working memory also known as scratch pad memory. Such memory may be erased once the task is completed, this is a very complex cognitive function that must be able to be maintained or be focused by us in light of distractions. For example, while using your working memory you are distracted by bumping your knee, getting into a conversation on the way to performing your task in fulfillment of your working memory.

So how does this working memory work? It has recently been shown that certain molecules interact within neural circuits in the brain which are responsible for working memory that occur in regions separate from long-term memory. Interestingly, this area of the brain used for working memory is significantly expanded in humans and non-human primates. A classic experiment involved the use of monkeys who in an experimental model had there brains monitored for neural firing (signifying brain activity) and the monkeys had to remember a visual cue presented to them for a brief period of time, this time period is known as the delay period-although the position of the cue changed from experimental trial to trial, it was shown that specific neuronal cell populations were involved in remembering the cue. During the delay period neuronal cells would fire at a high rate only when the visual cue was remembered or was extremely close to the position where the cue occurred.

It was further shown that specific neuronal cell populations were responsible for specific visual cue locations. Put another way, specific neuronal cell populations maintained a visual cue location. The firing of neurons is an excitatory process that is relegated to neuronal populations-in other words neurons work in a group that are close together in the brain and not in various locations of the brain, with respect to memory. Some of the responses of neurons (that is the firing of neurons which represent brain activity) are influenced by norepinephrine also known as noradrenaline which is responsible for sleep states and attention among other things-which bind to certain receptors such as a receptor known as a2A-AR (a2A adrenoreceptors). Inhibition of these receptors in has been shown to strongly impair stimulation of working memory. By using agonists- a pharmacological agent that mimics the natural activity of a molecule that binds to the a2A-AR causing activation scientists were able to show that an enhancing effect could be determined on memory.

In contrast, an antagonist, a pharmacological agent that inhibits a2A-AR activity decreased memory responses. It had already been shown that a molecule known as cAMP when active could inhibit working memory, by what was this molecules relationship to a2A-AR-did a2A-AR control cAMP or did cAMP control a2A-AR? Again using an agonist for a2A-AR it was shown that cAMP activity was inhibited, whereas the antagonist to a2A-AR resulted in increased cAMP activity suggesting that a2A-AR controlled cAMP.

Lastly, the final molecule involved in this process was a protein channel (this allows certain molecules to move into and out of cells)-HCN channels apparently opened with increased cAMP. This would suggest that with decreased or inhibited a2A-AR activity there is increased cAMP, and the opening of HCN channels which result in decreased working memory. In contrast, Increased a2A-AR activity leads to decreased cAMP and closure of HCN channels resulting in enhanced working memory. The implications of this find are important for a rational development of clinical therapies to treat disorders involved with memory.

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