Biochemical Interpretations of Neurophysiological Vectors

BIOCHEMICAL INTERPRETATIONS OF NEUROPHYSIOLOGICAL VECTORS HEINRICH WAELSCH* In the last twenty years biochemists working on neural tissue have shown an increasing interest in the correlates of brain function as presented and interpreted by neurophysiologists and physiological psychologists . After learning to appreciate the structural complexity of the nervous system, many of us have been willing and eager to understand the concepts offunctional brain science. This appreciation is an essential prerequisite to approaching the problem of functional biochemistry of the nervous system. We can take this occasion to remind ourselves that we are biochemists, dealing with the biochemistry of the nervous system, and that neurochemistry is only an abbreviation to be used when "biochemistry ofthe nervous system" is too long for the title ofajournal, or for the fifty-three spaces permitted for the title ofan NIH application. I hope that the time will never come when neurochemists will stop being biochemists. I know that this plea may be countered by the observation that the particular composition and complex structure of the brain, and the fact that the expression of its function is not biochemical * Professor ofBiochemistry, College ofPhysicians and Surgeons, ColumbiaUniversity, and Chief of Psychiatric Research (Pharmacology), New York State Psychiatric Institute, New York, New York. To Ralph W. Gerard with affection and in admiration, this essay is dedicated with many good wishes. Since his student days the author has listened to Ralph's voice wherever matters of interdisciplinary brain research were concerned. This article is an expression ofthis attitude and is meantas a token ofgratitude for Ralph's life work for this and future generations. This essay was presented aspart ofa series oflectureson"Biochemical Problems inthe Study ofthe Brain" at the Massachusetts Institute ofTechnology on November NS, 1964. The work discussed in this essay, and carried out in the author's laboratory, was supported in part by grants from the National Institute of Neurological Diseases and Blindness (NB-00557), from the U.S. Air Force Office ofScientific Research, and by a contract between the Office ofNaval Research and the Research Foundation for Mental Hygiene, Inc. (N.Y. State Psychiatric Institute Branch). I65 or mechanical in nature, justify regarding neurochemistry as a separate discipline. I should like to submit, however, that a separate discipline is characterized by its special methodology more than by anything else and that for the study ofthe nervous system we are using at present the techniques used by all biochemists. The question before us as biochemists is what makes the brain a brain; or, in more definite terms, how are the basic metabolic processes, such as energy generation and biosynthetic and degradative processes, modified by the complex structure ofthe organ? Where are there introduced new biochemical processes specific for neural tissue? Are these, by being specific for the nervous system, able to give us more insight into the relationship ofmetabolism to function than do the more universal biochemical processes? Does the fact that the functional aspects ofthe nervous system reside to a large measure in its membranes require a reorientation ofour biochemical thoughts not applicable to other organs ofthe body? It might be mentioned parenthetically that one of the values of developmental studies lies in the possibility of relating the appearance of biochemical processes during maturation ofthe brain to the emergence offunctional phenomena; but it should be kept clearly in mind that a temporal sequence does not necessarily imply a causal connection. One ofthe questions which will concern us in this essay is: When investigating basic biochemical mechanisms, can we today actually discern a biochemical circuit in the nervous system, which may occur concomitantly with the functional circuits from the axodendritic or axosomatic synapse to the cell body ofthe neuron to its own synapse and on to the next neuron, and so on; or, to express it differently, from the postsynaptic to the presynaptic membrane ofa neuron? In this paper, since I cannot cover the whole field ofneurochemistry, I shall try to select those aspects which involve recent data, those which seem to me of relevance to future physiological thoughts, and those in which my laboratory had some part. The attempt will therefore resemble one of those reconstructed mosaics—in one corner you see the hand of the...