592 PHYSIOLOGY: LORENTE DE N6 AND CONDOURIS PROC. N. A. S. zero and ceiling is an expression in the inverse sense of the rate at which the meta- bolic processes are operating. It is of interest that the dendritic membrane, given adequate oxygen, normal carbon dioxide and maintained at normal body temperature, should be set at a level of polarization so far from that at which maximal response is possible. One must suppose that dendritic conduction with decrement toward the tips is the normal occurrence and important to the normal working of the motoneurons. It would occur, for instance, not only in artificial "antidromic" action, but also in association with monosynaptic reflex transmission, for the presynaptic endings concerned are located on the cell body and the thick proximal dendrites,'1' 12 and the impulse generated there would travel toward the dendrite tips as well as along the axon to the periphery. 1 Renshaw, B., "Effects of presynaptic volleys on spread of impulses over the soma of the motoneuron," J. Neurophysiol., 5, 235-243 (1942). 2 Lorente de N6, R., "Action potential of the motoneurons of the hypoglossus nucleus," J. Cell. Comp. Physiol., 29, 207-288 (1947). 3 Lloyd, D. P. C., "The interaction of antidromic and orthodromic volleys in a segmental spinal motor nucleus," J. Neurophysiol., 6, 143-152 (1943). 4 Lloyd, D. P. C., "Electrical signs of impulse conduction in spinal motoneurons," J. Gen. Physiol., 35, 255-288 (1951). 6 Lloyd, D. P. C., "Note on the lateral dendrites of plantar motoneurons," these PROCEEDINGS, 45, 586-588 (1959). 6 Chang, H. T., "Cortical neurons with particular reference to the apical dendrites," Cold Spring Harb. Symp. Quant. Biol., 17, 189-202 (1952). 7 Lloyd, D. P. C., "Influence of asphyxia upon the responses of spinal motoneurons," J. Gen. Physiol., 36, 673-702 (1953). 8 Lloyd, D. P. C., "Mediation of descending long spinal reflex activity," J. Neurophysiol., 5, 435-458 (1942). 9 Lloyd, D. P. C., and A. K. McIntyre, "Analysis of forelimb-hindlimb reflex activity in acutely decapitate cats," J. Neurophysiol., 11, 455-470 (1948). 10 Lorente de No, R., A study of nerve physiology, Studies from The Rockefeller Institute, 131, 132, 1947. 11 Cajal, S. R., "L'anatomie fine de la moelle 6pinilre," Atlas der pathologischen Histologie des Nervensystems (Berlin: Hirschwald, 1895). 12 Sprague, J. M., "The distribution of dorsal root fibers on motor cells in the lumbosacral spinal cord of the cat, and the site of excitatory and inhibitory terminals in monosynaptic path- ways," Proc. Roy. Soc., B149, 534-566 (1958). DECREMENTAL CONDUCTION IN PERIPHERAL NERVE. INTEGRATION OF STIMULI IN THE NEURON BY R. LORENTE DE N6 AND G. A. CONDOURIS* THE ROCKEFELLER INSTITUTE, NEW YORK CITY Communicated February 23, 1959 The purpose of this communication is to reinstate an important piece of knowl- edge, the doctrine of decremental conduction in peripheral nerve, which existed in the classical literature, but which was lost some 35 years ago, when, mistakenly. physiologists of prestige deemed it erroneous. Downloaded by guest on September 30, 2021 VOL. 45, 1959 PHYSIOLOGY: LORENTE DE N6 AND CONDOURIS 593 Historical Background.-The concept of decremental conduction was enunciated in 1881 by Szpilman and Luchsingerl to explain the results of this experiment. A segment of the nerve of a nerve-muscle preparation is enclosed in a narcotizing chamber. The nerve is stimulated alternatively through electrodes outside the chamber, near the central end of the nerve, and through electrodes inside the chamber. Contraction of the muscle serves as indicator of the effectiveness of stimulation.t As the effect of the anesthetic (ether or alcohol vapor) develops, inside stimulation soon fails to cause a muscle contraction while the effect of out- side stimulation remains apparently unchanged. Nevertheless, if the stimulating current is increased, inside stimulation again becomes effective. As the anesthesia advances a stage is reached during which outside stimulation, however strong, fails to cause a muscle contraction, while strong inside stimulation still is effective. Finally, also strong inside stimulation becomes ineffective. During the recovery from anesthesia inside stimulation becomes effective first and some time later also outside stimulation becomes able to elicit a muscle contraction. That at the beginning of the anesthesia inside stimulation fails, unless the stimu- lating current is increased, indicates that the anesthetic raises the threshold of stimulation of the nerve without preventing conduction of impulses. Szpilman and Luchsinger did not follow this change in detail, but a few years later Werigo2 showed, in a systematic investigation, the accuracy of which cannot possibly be increased by the use of present-day techniques, that as the anesthesia progresses the stimulation threshold rises continuously. The increase in threshold, however, cannot explain the fact that after outside stimulation has failed, strong inside stimu- lation still results in the initiation of impulses, which cause the muscle to contract. To explain this fact, Szpilman and Luchsinger developed the concept of decremental conduction with an argument so lucid that it will be reproduced here with minor changes in terminology. Let a, b, c, d, ... be successive segments of a nerve. At a the stimulating current initiates an impulse of magnitude 'a, given by this equation 'a = 8AS)S (1) 'a measures the magnitude of the action current (one may take the height of the action potential as a measurement of that magnitude) which the impulse at a causes to flow; ,u(S) is a function of the stimulating current. The impulse at a initiates at b an impulse of magnitude Ib = alIa: The impulse at b initiates at c an impulse of magnitude I, = a2Ib, etc., so that during propagation the nerve im- pulse has the following successive magnitudes Ib = ajla= AualS IC = a2Ib = lUala2S (2) Id = a3I, = Malaa2a3S In equations (2) the a's are functions of the magnitudes I and of the properties of the nerve. It is clear that if Downloaded by guest on September 30, 2021 594 PHYSIOLOGY: LORENTE DE NO AND CONDOURIS PROC. N. A. S. a, = a2 = a3 = ... = 1 (3) the impulse will be conducted with constant magnitude. If, however, al, a2, a3, ... > 1 (4) the impulse will increase in magnitude during propagation. (Incremental con- duction occurs, for example, whenever the impulse passes from a zone of decrement into untreated nerve; see below, Fig. 7.) If, on the other hand, al, a2, a3,. < (5) the impulse will decrease in magnitude during propagation, i.e., it will be conducted with decrement; eventually it will be extinguished. The length of the segment of nerve through which an impulse may propagate itself depends on two factors, the magnitude that it has at the cathode of the stimulating current, and the magnitude of the a's. The smaller are the a's, the more rapid is the decrement and con- sequently the shorter the segment through which the impulse can propagate itself. Equations (1), (2), and (5) apply to nerve, which has been submitted to the action of anesthetics. Outside stimulation fails, while inside stimulation still is effective, when the values of the a's are such that the nerve impulse can propagate itself through half the length but not through the entire length of the narcotizing cham- ber; inside stimulation fails when the values of the a's are such that the impulse can no longer propagate itself through half the length of the chamber. During the recovery the values of the a's increase progressively so that the impulse again becomes able to propagate itself first through half the length and then throughout the entire length of the chamber. The remarkable fact should be emphasized that according to the doctrine of decremental conduction anesthesia does not block conduction because it abolishes the ability of the nerve fibers to produce impulses; anesthesia blocks conduction because it creates the conditions for decremental conduction and the nerve impulse is extinguished during propagation through the treated segment. On the other hand, it should be emphasized that in Szpilman and Luchsinger's formulation no definite statement was included regarding the value of gA(equation 1) in normal nerve. It was not until some 30 years later that the crucial nature of this problem could be understood. The doctrine of decremental conduction survived a 30 year long period of discus- sion and elaboration by a large number of physiologists. During this period weighted objections were raised against it by Werigo,2 but the objections were positively removed by the work of Dendrinos3 in Hering's laboratory and by the work of a number of authors (Frbhlich, Boruttau, Ishikawa, etc.) in Verworn's laboratory (cf. literature in Verworn4). The vast majority of those experiments were done with the classical techniques of comparing the effects of stimulation out- side and inside the narcotizing chamber or determining the length of the segments through which at various depths of anesthesia the impulses can propagate them- selves, but in 1912 Adrian5 described a new type of experiment (see below, Fig. Downloaded by guest on September 30, 2021 VOL. 45, 1959 PHYSIOLOGY: LORENTE DE N6 AND CONDOURIS 595 7,1 , II), so elegant and so convincing, that by itself it was sufficient to establish the doctrine of decremental conduction upon sound foundation. After decremental conduction had been securely established, i.e., after it had be- come clear that the magnitude of the nerve impulse could be measured by the length of the zone of decrement through which the impulse can propagate itself, it became possible to attempt to determine for normal nerve the relationship of the magnitude of the nerve impulse to that of the stimulating current. Since, in experiments done with the narcotizing chamber technique (Fig.