The Monday Afternoon Lecture
The Chemistry of the Brain David S a m u e l Director, Center for Neurosciences and Behavioral Research Weizman Institute of Science, Rehovot, Israel
1) The existence of excitable
Abstract Durina the ~ a s 20 t vears, there have been great advances in neurochemistry and psychopharmacology,-which provide a basis for understanding some aspects of mental activity in s (a) t h e identification of molecular terms. ~ e c e n i t r e n d &e: a n increasing number of small molecules-biogenic amines, peptides, amino acids, etc.-which are involved in the transmission or modulation of nerve impulses, (b) the synthesis of thuusunds of pqrhoartive drugsused (;,r research or [he t r w t m e n l oldisorder, (lithe brain, irl t h r iwlation and ~ I I rification of many hrain specific proteins and glycoproteins, which form the memhrane-bound receptors, enzymes and ion d Proeress has been greatest in channels in t h e l i ~ i function. the search for the biological basis of ieurological disorders and of mental diseases. In addition, following some decades of research in p h y s i o l o ~and psychology, something is also now known about the chemistrv of vision. of vain and of sleev. of addiction to alcohol and to drugs, andbf the aging of the biain. Very little is yet known about the mechanism of learning and memory, b u t techniques are now being developed t o tackle this last frontier.
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cell-neurons-which make up same 20% of the total number in the central nervous system. These, unlike other cells in the hody, donot divide or multiply-they just increase in size and complexity. The nan-proliferatian of neurons is the major cause for the irreversibilitvof hrain injuries, for some of the prohlems of senility and" of , many neurological diseases. I 2) The existence of a complex network of interneural connections-axons and den- I drites which link the brain in avast network, externallyto the sensors (eyes, ears, tongue, nose and skin, etc.) and to all the muscles and internal organs of the hody. Inside the brain, each neuron is connected to thousands of others in a complex pattern determined, to a large extent, genetically. This network is, however, modified during the course of the growth and development of eachorganism (man or mouse) by its accumulated exoerieuces.
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Selected Paragraphs to operate the ion pumps used to transport sodium, potassium, Plato once suggested that "there exists in the mind of man and chloride ions through the membranes of excitable cells in a block of wax and t h a t we remember what is important a s order to maintain a concentration gradient. Energy in living long as the image on it lasts, hut when the image is erased we systems means a supply of glucose and oxygen. Over 20% of the lorget." oxygen inhaled by a human being is carried by the blood to the Our knwvledge of the rhwiistry, physiology and analurny brain by cerebral blood flow (CBF)-although the hrain, in most 01 rhe hrain uf both ;inim.~lsand men, has i n d ~ e didvmired mammals, weighs only 1or 2% the total hody weight. This fact e\.en rurthtr 3inw then hur rhe link has alill ntlt I ~ c mmnde accounts for the sensitivity of all living organisms to the supply hetwwn these discipline, and hl~mimp i ) ~ h h g yor anininl of oxygen-serious mental defects become apparent after a few minutes of interu~tionin oxygen and death occurs after I~ehwior. nvmlc lime tried 10 iurrc thi, link. 11ut the - ~ - - ~ Man\. ~ . . su~ply, ten minutes. coq,plexity of the brain, as well as t h e roie of compo4) The most exciting feature of the chemistry of the hrain is the sition and hormonal action, are still not understood. I n addiscovery and identification of some 20 small molecules, the dition, the chemical effects of prenatal and early experiences, neurotransmitters, found only in the nervous system. These exposure to various neurotoxins, and even viruses are still a provide a very efficient all-or-none mechanism for the transmystery. However, remarkable advances have been made in mission, modulation, and control of the flow of bioelectricity, psychopharmacology-particularly in the development of i.e., ion gradients, throughout the neuronal network. At the drugs for the treatment of many mental and neurological appropriate time apulse, or quantum, of afew thousand molediseases. W e d o also know a great deal more about the basic cules of each transmitter is released from each nerve cell terminal across a small gap-the synaptic cleft-separating each chemistry of the brain. First of all, since World War I1 there neuron from the next. On reaching the other side the neurohave been great advances in molecular hiology-in nndertransmitter molecules activate appropriate receptors, probably standing r h e c u m ~ ) ~ , i i t i o n a n d d y n a m i ca11 s ~ ,living ~ t t llc, illembedded in the membrane of the second nerve rluding rhe 101'cell;in the human brt~in.T h i i ~ ~ ~ ~ ~ I ~ r ~ t , i l i < l i l ~glycoproteins, g cell, or muscle. So far only the acetylcholine receptors have been inclndis the structure and function of the cellnucleus and of isolated and purified, but chemical activity at the synapse is t h e nucleic acids (DNA & the various types of RNA), the known to occur constantly, day and night, throughout the lifemechanisms of transcription, translation, and protem synspan of an organism, in millions of different synapses every thesis, the action of a great many enzymes and the role of cell second. This is reallv the basis of the action of. control hv, .. the membranes. However, there are four unique features which brain-blood pressure and heart beat, breathing, eating and drinking, sleep, movement, sexual activity, and much else. distinguish brain cells from nearly all others. ~~
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Volume 59
Number 2
February 1982
93
