Friday, January 11, 2013

The Signal And The Noise In Learning And Memory

When my younger brother began taking piano lessons, my mother attempted to learn alongside him. Several months later, she could only ever play all twelve bars of ‘Little White Pony’ fluently, while my brother had moved on to more advanced pieces.

“It’s easier to learn when you’re young,” she explained dismissively. She eventually gave up trying to learn because, she said, at her age it would take much longer.

Was her logic flawed? Very- my mother has never been played any instrument before, is not particularly musical (sorry, Mom), and only practiced for about 15 minutes a week. Many believe, however, that there may be a kernel of truth in the claim that children learn quicker than adults- or at the very least, that they learn differently. Now, a new study suggests that there may be a physiological basis for this discrepancy.

As explained in a recent blog entry, repeated activation of a neuron is like weight training- with every ‘rep’, or activation of a neural circuit, the connection between the two neurons grows stronger. The next time the same circuit is activated, the neurons are more responsive to one another. This process and the changes which accompany it at the level of the synapse, the space between two neurons, are known as long term potentiation (LTP). LTP is important for memory and learning, which are both regulated in a part of the brain called the hippocampus. Long term depression (LTD) counters the effects of LTP by making a synapse weaker, eventually culminating in the removal of that synapse once it has been sufficiently crippled.

Artistic rendering of a neuron. Image credit:

Once again, let’s revisit the importance of NMDA receptors and their role in LTP and LTD. NMDA receptors appear to be essential for establishing LTP- without them, LTP fails to occur. They aren’t as essential for maintaining the effects of LTP, but that’s a different story.

NMDA receptors are composed of four subunits: two NR1 subunits and two NR2 subunits, NR2A or NR2B. The ratio of NR2A and NR2B subunits among neurons in the brain is dynamic, with NR2B being the more prevalent subunit until puberty hits, when the ratio begins favoring NR2A. NR2B subunits allow the neurons to ‘talk’ a moment longer by keeping the calcium (Ca2+) channel in the receptor open longer, creating stronger synapses. This characteristic of NR2B and its prevalence in younger brains, it has been hypothesized, may contribute to children’s superior ability to learn and create new memories.  

Dr. Joe Tsien and his colleagues at the Medical College of Georgia at Georgia Regents University decided to test whether the ratio of NR2 subunits correlates with the changes in learning and memory which occur with age. Previously, Tsien found that increasing levels of NR2B in the brains of mice made them ‘smarter’ and faster learners due to an enhanced ability for LTP. In a paper recently published in the journal Scientific Reports, Tsien and his team describe a study in which the opposite conditions were tested. Tsien and his team studied mice with adult ratios of NR2 subunits. They created transgenic mice with an increased ratio of NR2A in their forebrain, which included the hippocampus, to analyze the effect the altered ratio had on cognition in mice. The transgenic mice had normal short-term memory but their long-term memory was impaired.

The researchers had predicted that decreased LTP may be the cause of the long-term memory impairment in the mice, but they found that this process was unaffected. Surprisingly, they found that long-term depression (LTD) which leads to weakening of the synapse was disrupted. Our ability to learn and form long-term memories, it seems, is not only dependent on having strong synapses, but also being able to silence ‘noise’ from weaker synapses.

Most neurons are associated with thousands of synapses, and so there needs to be some way to refine the barrage of incoming information. When our synapses are overloaded with information, it is difficult to pick out the signal from the noise and so our learning and memory function is impaired. Imagine standing in an auditorium full of people and trying to hear a friend who has an important message for you at the opposite end of the room. If everyone is yelling all at once, it would be impossible to hear what they are saying; if the crowd is silent, or speaking barely above a whisper, you will be able to hear your friend much clearer. If a high ratio of NR2B in the brain is equivalent to giving your friend a megaphone, having a high ratio of NR2A subunits turns up the volume of the crowd.

Our brains are formed from billions of neurons which are in constant communication with one another; at this moment they are reading these words, storing away the knowledge (hopefully) obtained in this post, and- assuming you are still breathing- directing the many ‘housekeeping’ activities our bodies are carrying out every second of every day. The human brain is truly a masterpiece of organized complexity. It is fitting, then, that Tsien and his team coined the term ‘sculpting’ to describe the way in which the brain takes in and assimilates new information. Active synapses are strengthened, existing synapses are weakened, old synapses are cleared away- our minds are our masterpieces.

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