Typical curves of upper channel ac- tivity versus date are shown in Fig. | for Bismarck, N.D., and for New Or- leans, La. The constancy of the potassium-40 assay is indicated by the reproducibility of the results for the first 6 weeks. The peak concentrations given in Table 1 can be compared with the International Commission on Radiological Protection’s maximum permissible concentration for barium-140/lanthanum- 140 in drinking water of 300 muc/lit (3). The latter value is for continuous exposure for an indefinite period of time, while the exposure resulting from weaponstesting is of short duration. Un- like stronttum-90, barium-140 cannot present a cumulative hazard because of its very short half-life. Barium-140 has not been observed in any human sub- jects, although a search has been made for it. E, C. Anperson, R. L. Scoucu W. R. Fisuer, M. A. Van Ditia Los Alamos Scientific Laboratory, University of California, Los Alamos, New Mexico References 1. E. C, Anderson e¢ al., Science 125, 1273 (1957). 2. E. C. Anderson et al., Nucleonics 14, No. 1, 26 (1956); E. G. Anderson, JRE Trans. on Nuclear Sct. 3, 96 (1956). 3. “Recommendations of the International Commission on Radiological Protection,” Brit. J. 4, Radiol. Suppl. No. 6 (1954). C. E. Miller et al,, Nucleonics 14, No. 4, 40 (1956). 28 October 1957 Action of Blood-Borne Gamma-Aminobutyric Acid on Central Synapses When substances are identified in the brain, it is natural at the same time to inquire into their function. Thus they method, asin the topical application of strychnine (4) to fire brain areas, in order to map them, has gaimed it considerable respectability, this should not be extended to other uses. Thus, Kato {3}, in studying conduction in nerve, found it convenient to make use of mechanical stimulation by a miniature mallet, but there was no suggestion that Nevertheless, the actions of GABA have been studied almost exclusively by top- ical application. We have, therefore, wished to study the effects of blood-borne GABA and have resorted to the method we have previously used to help establish the roles of acetylcholine, adrenaline and nor-adrenaline (6), and serotonin (/) as neurohumoral transmitters in mam- malian brain. This has been the rela- tively close arterial injection in the common carotid artery serving effectively to bring across the blood-brain barrier rela- tively small doses which, therefore, on dilution in the systemic blood stream become subthreshold for peripheral ac- tions and consequently exhibit the cerebral actions in isolation or im relatively the peripheral actions and the resulting barrage of afferent impulses which bombard the brain. In this manner, by ac- response as evoked cortical potentials in the lightly anesthetized cat, we have demonstrated that GABA, when delivered through the natural route (that is, whenit is blood-borne), can, hike adrenaline, nor-adrenaline, and serotonin, inhibit synaptic transmission, It does this 7x; adrenaline, 15x; serotonin, 300 x. (2) have identified the latter as an active principle of factor I, which Florey positive wave or inverting the negative (GABA). Bazemore, Elliott, and Florey the surface negative evoked response is usually reduced without affecting the and McLennan (3) had extracted from wave Into a positive one. Comparison with serotonm brings out result serve to uncover any possible actions. Effects achieved in this highly ab- normal way are undeniable but difficult to interpret in terms of physiological function, even when specificity can be asssured. Although the usefulness of this 284 nator NEUROW METABOL 1 CONTROL [a] v Varying Threshold MAXIMUM EFFECT RECOVER’ G fa t was fe +9} I fohe = . . TEP rr ee =, eae “= « 50 pg} o, 1 9 ” on tO 3 AO Heconde Fig. 1. Cerebral synaptic action of gammaaminobutyric acid in a two-neurone intercortical (transcallosal) system. (Top) Potential factors in disturbed synaptic equilibrium. (Bottom) Potentials evoked in the cerebral cortex of the cat by electrical stimulation of the contralateral cortex every second. Gamma-aminobutyric acid was Injected into the ipsilateral common carotid artery. A further significant differences. The time course of the GABA action is faster in all respects, As the continuous plot of the surface negative evoked responses shows, the time of onset and the dura- tion of action are remarkably short. The latter suggests an enzymatic destruction of GABA as was supposed by Florey and McLennan (3) or a binding into an ' inactive state by adsorption as believed by Elliott (8). Successful interference with this enzymatic or this binding process would result in abnormal accumulation of GABA, which would be evi- . fs . oo sane * My A, yee 27 , , 8 one 2068 Pie. t GABAtmg.| 10 of fog* tT 8 ale. -% 30 50, v tT . T r ee. Jae wastes .e *, wee e »* DID o.5mg. 1 10 | D-14min. after 01 ° os oats + vet ae ® * Pe oe ° of serotonin, intermediate between that of nor-adrenaline and adrenaline, the reported by Purpura and Grundfest {7} sort is to paint a solution of the material upon the exposed cerebral cortex. The high doses thus applied and the unusually high concentration gradients that TRANSMISSION ‘METABOLISM __ —" — Production in doses of 50 to 500 ug/ke (Fig. 1); thus it has a potency of about 1/50 that case with serotonin (/), and such is now the case with gamma-aminobutyric acid One of the readiest methods of ac- Se pe Voryind SS estructon tivating cortical synapses through the transcallosal pathway and recording the Unlike the effects of topical application quiring preliminary information of this —_—/ pure form—that is, not complicated by transmitters. Such, indeed, has been the have inhibitory actions. @ Response Reception @ Vv BIOCHEMICAL FAULT that this mechanical stimulus played a part in propagation of the nerve impulse. series being nor-adrenaline, t; GABA, mammalian brain and had shown to ‘ 407939 (EXCITATORY 2 INHIBITORY} @ Tromemission o Liberctiga this was a normal way t@ activate or become candidates for various roles, in- cluding that of potential neurohumoral SYNAPTIG AGTIONS “T TT * . . v ° rT GABA Img! 10 pee ee eerste. ° 30. 50. 70 90 —— T rT fT a a E-23min. after D1 GABA Imgl Oo F 30 50 ee oe 4%, 2 as ° . e oh an. a woeats CPO, 1 o1® o.5mgl 10 t a T rUrF 30 50 70 t T Tt T T G~44min. after Dit? * ean oe * * 7 . as* ce, * Fe ae GABA Img.1 10 Pe petaEOENET e 30.50. . 70. a 90 Fig. 2, Augmentation of GABA cerebral synaptic inhibition by dilantin. Negative cortical spike heights from travscallosal system potentials evoked by. cotitralateral cortical stimulation (one per second). Injections were made into’ the ipsilateral common carotid artery. SCIENCE, VOL. 127