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).

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

CONTROL

[a]

Varying Threshold

MAXIMUM EFFECT

RECOVER’

G fa

t was

fe +9}
I

fohe
=
.
.
TEP
rr
ee
=,

eae

“=

50 pg} o,

”

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.

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

sane * My

A, yee 27
,

one 2068

Pie.
t

GABAtmg.| 10
of

fog*

ale.

50,

ee.

Jae

wastes .e *, wee

»*

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

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

*
.

. v °
rT

GABA Img! 10

pee

eerste. °

30. 50. 70 90
——

E-23min. after D1

GABA Imgl Oo
F

4%, 2
as ° . e
oh an.
a woeats CPO,
1

o1® o.5mgl 10

rUrF

30 50 70
t

G~44min. after Dit?
* ean

oe *

* 7

as* ce, * Fe

GABA Img.1 10

petaEOENET
e

30.50.

70.

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

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