Sleep Needed for Memory

Got kids or grandkids in school? Odds are they are not getting enough sleep, and it is hurting their learning and grades. This is a special problem for older adolescents. At this age, the biological clock shifts and makes them stay up too late if they need to get up at 6-7 A.M. to get ready for school. Kids this age need about 9 hours of sleep a night. So what is the relationship to learning? Two things:

1. When students are drowsy during class, they can't focus attention and will not encode new information effectively. Sometimes they even fall asleep in class, which means they are not encoding anything.

2. Sleep provides an uninterrupted mental environment in which the brain rehearses the events of that day. As documented in dozens of peer-reviewed research reports, this rehearsal promotes consolidation of fragile temporary memory into more permanent form.

Now, two new studies reveal what happens during sleep to accomplish this consolidation task. Just as a computer writes to a hard drive or CD for permanent storage, the brain has to have a storage mechanism. Information in the brain resides, in real time, in the form of nerve impulses flowing around in certain networks. As long as the impulses are present, the memory is present. But if the impulse patterns change, then the information they represented is lost—unless the impulse pattern was played long enough to cause structural change in the corresponding circuitry. Scientists have known for several decades that information is stored in the junctions (synapses) between neurons. We used to think that the synapses involved in learning can grow from repeated use. Impulse patterns representing the day's experiences are replayed during sleep, providing the repetition needed to stimulate growth in the corresponding synapses. But new evidence suggests that learning does not cause the involved synapses to grow, but rather prunes them during sleep to remove irrelevant information.

One of the new studies showed that synapses in mice change structure and chemistry during sleep. In sleep, the synaptic gaps become narrower and the number of neurotransmitter receptors decreases. This may constitute a pruning process. Synapses receive multiple inputs, and a pruning process could help remove irrelevant and interfering information, thus causing a relative magnification of the memory of information being rehearsed during sleep. Another way to think about it is that sleep may provide a mechanism for "smart forgetting."

The second study by another group, also in mice, confirmed this evidence of pruning and further implicated a particular receptor, the one for the excitatory neurotransmitter, glutamate. The investigators even identified the gene that is activated to remove excess glutamate receptors.

The practical application of these findings for school children is that the more they are allowed to sleep, the more time there is for sleep to cause the synaptic changes needed to store the day's learning in the "brain's hard drive." The other, more general, implication of these studies is that the brain's anatomy and physiology are readily changed by experience, a well-established fact that scientists call "neural plasticity."

Readers may be interested in "Memory Medic's" book, Memory Power 101 (Skyhorse) and his more recent book, Mental Biology (Prometheus).

Sources:

de Vivo, Luisa, et al. (2017). Ultrastructural evidence for synaptic scaling across the wake/sleep cycle. Science.  355, 507-510.

Diering, Graham H. et al. (2017). Homerla drives homeostatic scaling-down of excitatory synapses during sleep. Science. 355, 511-515.

Brave New World of Gene Change in Brain

In recent years scientists have discovered mobile pieces of genetic material that move around inside cells. These pieces are called retrotransposons. They can copy themselves and insert near and into DNA and thus induce mutations. Australian research recently reported in the journal Nature reveals that retrotransposons can alter the genome of human brain cells. In fact, retrotransposons more effectively penetrate neuron genes than those in blood cells that were used for comparison. Thousands of retrotransposon mutations were seen in two of the five areas examined from brains of human post-mortem donors.

Though these pieces of DNA are not genes, they interact with genes that hop around to different sites within a chromosome (perhaps you heard about Barbara McClintok’s 1983 Nobel Prize winning discovery of “jumping genes”). All cells have enzymes that cut transposons out of a string of DNA, which then insert back in at other locations in the DNA. Sometimes the cut includes an adjacent gene along with the transposon, and thus when reinsertion occurs the gene hitchhikes along to the new location. The jumping around is not random; it occurs preferentially into active protein-coding regions, even sometimes in a different chromosome. The potential for changing function is enormous, yet we don’t know just what functional consequences occur. We do know that the process is most common in humans and higher primates.

We have known for some time that all cells are influenced by epigenetic effects; that is, events in the environment can alter the genome. The mechanism may well involve retrotransposons. Gene manipulation may be especially robust for altering learning and memory. It may be no accident that retrotransposon mutations were seen in human hippocampus, the brain region most directly involved in forming memories and the one part of the brain where new cells are continuously born in adults. Memory of learned events results from more or less lasting changes in the junctions (synapses) among cells in the circuits that processed the learning. These lasting changes are enabled by new protein production in those synapses. That protein is under genetic control (thus a memory can be sustained because the genes can replace any protein that degrades over time). 

Aldous Huxley, 1894-1963

The implications of this discovery for learning and memory―and brain function in general―are inestimable. More importantly, and here is where the “Brave New World” comes in, there should be the potential for manipulating gene functions in predictable and lasting ways by using synthetic transposons (which should be easy to manufacture).  Transport of synthetic retrotransposons into neurons might be accomplished by packaging them with a harmless virus; the basics of “transfection” technology are already well established. The hard part will be in discovering what transposons produce desired changes in brain function. But it seems reasonable to test various retrotransposons in the hope that some can be found that will help to cement or magnify memories and perhaps others that erase unwanted memories, as occur in post-traumatic stress syndrome. There is a potential down-side, however. Some retrotransposons may be a cause of cancer.

Source:

Baillie, J. K., et al. (2011) Somatic retrotransposition alters the genetic  landscape of the human brain. Nature. 479: 534-537.

NOTE: My new book on practical ways to improve memory will be released on August 1. You can order now at http://www.skyhorsepublishing.com/book/?GCOI=60239100060310