In search of memory

My main criticism of A.J. Jacobs’ The Know-It-All is his lack of understanding of science and that makes him only half qualified to cover Encyclopaedia Britannica.  I feel I was not alone after reading Joe Queenan’s “The Know-It-All: A Little Learning is a Dangerous Thing” in the New York Times book review (10/3/04)  Jacobs’ rebuttal (also published in the same book review) proves he is indeed a good writer, but is one who cannot take criticism; if I were him, I would write a different rebuttal, borrowing or even ‘plagiarizing’ Samuel Johnson’s sharp tongue and wit of insults.

Jacobs wrote if he doesn’t have ‘waxy pallor’ he doesn’t have aplastic anemia. Not only did he not tell the essence of aplastic anemia, he laid bare his ignorance in understanding medicine.

Knowledge is yours only when understood (and remembered, since the topic is 'memory'.)

My 1987 EB defines memory as “the retention and retrieval in the human mind of past experiences.”  This is not quite correct, as animals obviously have memory, too; and the model organism that Eric Kandel used in studying memory is a marine organism Aplysia.  Kandel was awarded a Nobel Prize in Medicine in 2000 for elucidation of the molecular mechanism of memory.  Here is the story:

In his 2002 Nobel Lecture (“Nature’s Gift to Science”), Sidney Brenner talked about the importance of choosing a model organsim for a given project.  He used the ‘elegant’ C. elegans (a nematode with about 1000 cells in all, among them 302 cells in nervous system, its genome is only 20 times that of E. coli).  Alan Hodgkin (1963 Nobel Prize in Medicine for ionic channels in nerve cells) used squid for its “giant nerve fibers, which may be as much as a millimeter in diameter.”  and Kandel used Aplysia, which has only 2 x 10⁴ neurons (nerve cells) in its brain, comparing to 10¹² that human brain has, and its capability of simple learning.  Aplysia also has very large nerve cells in brain so the microelectrodes can be inserted.

The most striking finding is that short term memory doesn’t require the protein synthesis whereas the longterm memory does, although both use the same synapses. Thus whenever we remember something for the long-term, our chromatin (complex of DNA and protein) structure in brain changes and synaptic strength enhances, and the neural networks of the brain are not fixed but dynamic.

Kandel said ‘repetition’ and ‘practice makes perfect’ is the only sure way to convert short-term to long-term memory.  This was well documented in his 48-page Nobel lecture or one-hour video.  This may be the best ‘take home’ message of this writing.

A synapse is how the nerve cells communicate each other:  it usually works by neurotransmitters which are secreted by a presynaptic cell, sending the message to the postsynaptic cells.  We have hundreds of billions of nerve cells, one can imagine how many synapses that we have.

Signal transduction of synapse involving memory storage, complex though it can be, is where the beauty of science lies; there is CREB-1 which is a stimulatory protein, and inhibitory CREB-2.  That is, for a memory to be stored, CREB-1 has to be activated and inhibitory constraint has to be removed. (i.e. CREB-2 to be inhibited)

This may explain why some people can remember well without effort and others have trouble remembering.  Kandel said (in the lecture video, I cannot find this in the text format.  I have noticed that, the text formats of many Nobel lectures are somewhat different from the videos) “I have a friend, Sigbund ?, seems to remember every thing, I always thought he was a bright kid at Columbia [Kandel is at Columbia University], now I am afraid he is a mutant with a specific defect in CREB-2 protein.” (laughter erupted)

A few days ago, either CNN of Fox news interviewed a man who can remember everything happened any given day in his life. (He didn’t get 100% correct.)  He most likely has a defect CREB-2 protein (due to a mutant CREB-2 gene) and if one is without an inhibitory constraint, one remembers every thing.

Kandel became philosophical when he explained why there is a need of inhibitory CREB-2 gene when it comes to memory storage, “It is clearly evolutionary advantage for an animal to learn and store in long-term memory only facts important for survival, rather than retaining everything.”

By now one should get an idea why memory capability is not considered a component of intelligence (analytic, creative, or whatever) by the experts in this field.  And this is why we have those absent-minded professor anecdotes.

Shortly after Einstein arrived at Princeton’s Institute of Advanced Study in 1939, he was a hot pursuit of paparazzi [did we have paparazzi in his days?] so school officials were asked not to give away Einstein’s where about.  One day the university president received a call asking where Einstein lived, the president responded by saying he was not supposed to tell, an embarrassing whisper came from the other end of the line, “but, this is Einstein” who forgot where he lived and happened to carry with him the president’s phone number [I doubt he could remember the phone number.]
 

Alzheimer’s disease is a clinical disease characterized by gradual decline of cognitive function from a previously higher level and the impairment of recent memory.  There are no laboratory tests can confirm it, although an MRI finding of hippocampal atrophy is suggestive, but not specific or sensitive.  It is of interest that synapses involving memory and learning are highly concentrated in hippocampus.

In his memoir, In Search of Memory, Kandel spent many pages praising the pioneer in neuroscience, Santiago Ramỏn Cajal who shared the 1906 Nobel Prize in Medicine with Camillo Golgi to whom Kandel had many negative comments, though.

Cajal proposed in 1894 “a theory of memory storage: memory is stored in the growth of new connections [synapse in modern term]” A great mind tends to have prescient idea, it never fails.