Using the glass electrode assembly connected with the femoral artery in dogs, the cyclic fluctuation of pH of the circulating arterial blood was observed under varying rates and depths of respiration. The frequency of fluctuation coincided with the respiratory rate, and the size of fluctuation was magnified as respiratory frequency was decreased. When the breathing was increased in depth without changing the frequency by CO₂ inhalation, a smaller range of pH fluctuation was resulted.

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The effects of GABA, its derivatives and their related compounds on the isolated ileum of the guinea-pig, rabbit and cat were investigated.
1. GABA had three types of effect on the guinea-pig ileum under various conditions; i.e. sustained tone-increasing, or relaxing or transient tone-increasing one followed by relaxation.
2. Other ω-amino-acids, such as glycine, δ-aminovaleric acid and ε-aminocaproic acid had no effect. Only β-alanine at 10^-2 M/1 produced sometimes only a slight relaxation.α-amino-n-butyric acid and β-amino-isobutyric acid had no effect.
3. 4-Aminobutanol and N-methyl-4-aminobutanol at very high concentrations had a slight stimulant action, although n-butyric acid had no effect.
4. N-Substitution with acetyl, phenyl, butyl or methyl group reduced relaxing activity of GABA.
5. Methylesterification of GABA strengthened its stimulant activity. The stimulant effects of methylesters were antagonized by atropine.
6. As the chemical structure of GABA became more similar to that of Ach, its stimulant activity became progressively higher. However, even N-trimethyl-GABA-methylester, whose effect was strongest among the methylesters, was by far weaker than Ach.
7. N-Ethylation and N-butylation weakened the stimulant effect of GABAmethylester and N-phenylation reversed it into a relaxing one.
8. N-Methyl-GABA-ethylester had a weaker stimulant effect than N-methyl-GABA-methylester, and N-methyl-GABA-butylester and N-methyl-GABA-benzylester had a marked relaxing effect.
9. N-Methyl-GABA-ethylester had a weak relaxing action in lower concentrations, but a stimulant effect in higher concentrations. On the contrary, N-methylbutylester had a weak stimulant effect in lower concentration, but a strong relaxing one in higher concentrations.
10. The effect of GABOB was similar to that of GABA. But, the effects of GABOB and GABOB-methylester were weaker respectively than those of GABA and GABA-methylester. OH-group at β-position reduced the activity of GABA.
11. Nicotinic acid, isonicotinic acid and their methylesters produced a slight relaxation.
12. The rabbit ileum responded to above mentioned GABA-derivatives with similar manners, but with less sensitivity than the guinea-pig ileum.
13. The cat ileum reacted to these substances with almost the same manners and sensitivity as the guinea-pig ileum.
14. The relation between the structure and the effects of GABA was discussed.

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The mechanisms of inhibitory and facilitatory effects of the brain stem reticular formation, upon motor and autonomic reflexes, such as monosynaptic reflex (MSR), polysynaptic reflex (PSR) of extensor and flexor motoneurons and galvanic skin reflex (GSR), were analyzed by stimulating single points in the brain stem with single or repetitive pulses. Experiments were conducted on 65 adult cats decerebrated at precollicular-chiasma level.
1. By repetitive stimulation of the same single points in the brain stem, generalized inhibitory and facilitatory effects upon these motor and autonomic reflexes were observed in the medial medulla oblongata and pons respectively, whereas from the lateral medulla oblongata and midbrain various combinations of inhibitory and facilitatory effects upon above noted 5 reflexes were obtained, with some differences of effects of laterality and with some special interrelationships between these effects.
2. Following single pulse stimulation of the brain stem, five different types of effect upon extensor MSR. were obtained. Among them, diphasic inhibitory type, viz., initial slight increase of amplitude of MSR followed by its marked decrease, was observed in relatively high percentages by stimulating points in the medial and lateral medulla oblongata and midbrain, from where simple inhibitory effects were induced by repetitive stimulation.
3. In regard to GSR, there was a close parallelism between the effects of brain stem stimulation upon GSR elicited by radial nerve stimulation and upon spontaneous variations of skin potentials especially in the case of inhibition.

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In order to analyse more precisely the effects of single pulse stimulation of the brain stem upon monosynaptic reflex, effects upon individual motoneurons were investigated by means of the firing index method of LLOYD and MCINTYRE. Effects upon gamma efferents were also examined by picking up afferent discharges of group Ia, II and Ib fibers from dorsal root filaments in comparison with the effects upon monosynaptic reflex to the same muscles.
Experiments were conducted on 42 adult cats decerebrated at precollicularchiasma level.
1. Two kinds of firing index curve, a monophasic positive and a monophasic negative, were obtained from ventral root filaments by stimulation of single points in the brain stem which gave diphasic inhibitory effect on the monosynaptic reflex by single pulse stimulation. These patterns of firing index curve resembled the excitatory and inhibitory post-synaptic potentials of the motoneuron, respectively, in time course.
2. Effects of brain stem stimulation upon afferent discharges of group Ia, II and Ib fibers from extensor muscles were investigated separately. It was observed that afferent discharges of group Ia fibers showed a tendency to respond in the same way as the effect on monosynaptic reflex to the same muscles, whereas the result was almost reversed in the case of group II fibers.
However, it is noteworthy that, in relatively high percentages, no effect resulted upon these afferent discharges from stimulation of the points which gave distinct effects upon monosynaptic reflex.

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Specific properties of the electrical activity of the auditory system were studied on unanesthetized curarized cats, and the following results were obtained.
1) The electrical activity level of the auditory system changed independently from the other neocortical areas and paleo-and archicortices.
2) Tone stimulus of adequate intensity produced the localized activation in the auditory area.
3) Low voltage fast activity in the auditory area occurred by high frequency electrical stimulation of the medial geniculate body.
4) The spontaneous spindle bursts of the auditory area were frequently accompanied by the spindle bursts in the ipsilateral medial geniculate body. In the spindle stage of EEG, the spindle bursts were induced by click both in the auditory area and medial geniculate body. The pattern of the induced spindle bursts was similar to that of the spontaneous spindle bursts.
5) The induced spindle bursts in the auditory area by single shock stimulation of the ipsilateral medial geniculate body, and conversely, the spindle bursts in the medial geniculate body induced by single shock stimulation of the auditory area were observed. The induced spindle bursts in the auditory area and the spindle bursts in the sensori-motor cortex induced by single shock stimulation of the caudate nucleus did not interfere each other.
6) The spindle-like discharges in the midbrain reticular formation sometimes occurred together with the spontaneous spindle bursts in the auditory area and medial geniculate body.

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1. Experiments have been carried out to analyse the way in which a bacterial pyrogen causes a biphasic pattern of fever in rabbits.
2. It was just during the interpolated period between the first and the second peak of fever, that vasoconstriction was observed in the denervated ear with a larger dose of pyrogen. After adreno-demedullation this vasoconstriction developed more slowly and to a less degree.
3. Moreover, it was principally during the period of the first declining phase of fever that hyperglycaemia was seen.
4. A marked fever developed in a rabbit in which the participation of skin vessels was largely or completely prevented.
5. There was a tendency in intact animals that skeletal muscular activity, as indicated by E. M. G. from the back of the body, was low throughout the period between the two peaks compared with the other periods of the induced fever.
6. A biphasic fever was more likely to occur for the low level of temperature in a thyroidectomised rabbit.
7. It may be concluded that the biphasic pattern of fever is caused by a temporal suppression of a fever which would otherwise be monophasic. The adrenal medullary secretion may be suggested to play an important part in such an effect.

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1) A denervated jejunal loop of dogs is kept in a state of complete anemia by perfusing the blood vessels of the loop with TYRODE solution for varying periods from 1/4 to 4 hours. The blood circulation of the loop is then reestablished, and the intestinal intrinsic reflexes are traced at intervals. At the end of the experiments intramural ganglion cells of the loop are examined histologically.
2) Where complete anemia of the loop is continued for 4 hours, the intrinsic reflexes remain abolished permanently, almost all the intramural ganglion cells of the loop undergoing the degenerative changes. It may be thus confirmed that the intrinsic reflexes are produced by a mechanism involved in the intramural ganglion cells.
3) There obviously occur the rhythmic contractions in the loop described above. Consequently it may be concluded that the rhythmic contractions of the small intestine are essentially of myogenic origin.

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Slow muscle responses induced by stimulation of the brain-stem reticular formation, which was confirmed in the previous report to send off spontaneous and specific impulses for the maintenance of the posture, were observed mainly in extensors in toad forelimb.
1. A typical pattern of muscle responses so excited was obtained by the liminal stimulation of appropriate sites in the reticular formation (tectal and bulbar). This was composed of two or more successive slow muscle responses. As the stimulation strength was increased, twitch muscle responses appeared overlapping on the slow responses. However, when the stimulation was submaximal, there was found often an intervening slow response in the silent interval.
2. The latency for the 1st muscle response caused by stimulation of the tegmental reticular formation was 25.7 msec. in the mean, which was always shorter by about 5 msec. than that by the bulbar stimulation. This interesting fact was easily recognizable from that accelerating impulses sent from the bulbar reticular formation were intermediated by the tegmental formation, where the efferent fibres start. Impulses sent from the tegmental formation reached in about 16.5 msec. to the contralateral 3rd spinal ventral horn, from which about 5 msec. was spent to the brachial nerve plexus.
3. Supplementary experiments were carried out briefly on flexors and the gastrocnemius muscle. The reticulum stimulation induced muscle responses in flexors only on the side contralateral to stimulation but in the gastrocnemius bilaterally. However, slow muscle responses were not easily detectable.
4. The time interval between the 1st and the 2nd responses of those muscles was characteristic of the muscle group concerned; e. g., about 100 msec. in forelimb extensors, about 150 msec. in flexors and 110 msec. in the gastrocnemius muscle. It was discussed that these rhythmicities may be due to the property of motoneurons innervating those muscles.
I wish to express my sincere thanks to prof. R. ITO for advice and criticism.

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1. In unanaesthetized acute spinal cats, intravenous injection of GABA above 0.30mg/kg consistently depressed the extensor monosynaptic reflex, while the flexor monosynaptic reflex was usually facilitated. GABA action gradually decreased when systemic administration was repeated with short intervals.
2. These actions of GABA was not demonstrated in decerebrate cats.
3. The effect of GABA on the flexor monosynaptic reflex was remarkably altered by changes in the internuncial activity produced by cutaneous, Group II and III afferent conditioning volleys.
4. GABA action was not influenced by Group I afferent and antidromic axoncollateral conditioning volleys.
5. Nembutal anaesthesia resulted in elimination of GABA action. Strychnine abolished or reduced the facilitatory effect of GABA on the flexor monosynaptic reflex.
6. It was concluded that GABA may selectively block some excitatory interneurones which are intercalated in the reflex pathways of Group II and III fibers of muscle nerve and of some cutaneous afferent fibres and are tonically controlled by suprasegmental activity.

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1. Bovine dorsal root, dorsal half of its spinal cord or guinea-pig's whole brain was extracted with about 70% ethanol at room temperature. When the extract was incubated with trypsin after concentrated in vacuo, substance P (SP) present in the original extract was destroyed but gut-stimulating activity apparently still remains, which could be ascribed to a new component (CT).
2. CT could be extracted by the procedure quite similar to ROCHA e SILVA's extraction method of crude bradykinin and seemed to be of polypeptide nature.
3. The gut-stimulating activity of CT on guinea-pig ileum was barely affected by atropine, tryptamine, cocain, tetramethylammonium, hexamethonium, morphin, GABA and ε-amino-n-caproic acid and so resembles to that of SP. But contraction produced by the former is slower, not abolished by previous administration of SP, nor potentiated by LSD, but depressed by high dose of pyribenzamine.
4. Using guinea-pig's ileum, hen's rectal caeceum, and rat's uterus and colon, it was proved that action of CT is rather similar to that of plasma kinin and different from that of substance P.
5. It was found that the higher the SP content of the tissue, the more CT was obtained on incubation with trypsin, dorsal spinal cord and small intestine giving higher CT activity, skeletal muscle and ventral cord lower one.

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The functional relation between the olfactory bulb and the mesencephalic reticular formation (RF) was studied in curarized rabbits. The results obtained in the acute experiment were confirmed in the chronic experiment.
1. High frequency stimulation in the RF suppressed the intrinsic and the induced waves of the olfactory bulb. Peripheral arousal stimuli were sometimes effective in causing a similar changes in the olfactory activity.
2. The excitable spots suppressing the activity of the bulb were distributed diffusely in the RF. They were also found to extend in the hypothalamus.
3. RF stimulation failed to modify the negative wave potential of about 40 msec duration evoked in the bulb by electrical stimulation of the olfactory mucosa.
4. Complete destruction of the olfactory mucosa and section of the anterior commissure were unable to influence the suppression of the olfactory activity due to RF stimulation. On the other hand, neuronal isolation of the bulb abolished the reticular influence.
5. In contrast to the neocortical EEG, the olfactory activity failed to show a release phenomenon upon acute destruction of the RF.
6. In the chronic experiment peripheral arousal stimuli were found to suppress the intrinsic activity of the olfactory bulb in the same manner as in the acute experiment.
A part of the expense of this work was defrayed by a grant of the Ministry of Education.

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1. The behavior of the isolated sartorius muscle of the frog in calcium-deficient medium has been studied by recording the transmembrane potentials of adjacent two fibers simultaneously.
2. Accompanied with rise and fall of the educed fibrillation, the adjacent fibers exhibited different grades of electrical activity, but most of their activity appeared synchronized in rhythm particularly at the crest of fibrillation.
3. A few different types of small waves were recorded during the spontaneous activity; the slow rising depolarization preceding spike potential (pacemaker-like potential), the small fast wave with short duration produced by electrotonic spread of action current of the neighboring fiber (interaction potential), and the long slow wave of unknown origin.
4. The interaction potentials were mostly positive (depolarization) but sometimes negative (hyperpolarization) or diphasic as expected, appearing in two or three rhythms simultaneously and piling up on each others.
5. Mechanisms of the fibrillation were discussed obtaining a conclusion that some fibers, acting as pacemakers, were excited spontaneously and the excitation was transmitted to adjacent fibers through low-safety-factor, intercellular, electrical connections.
Cordial thanks are due to the Rockefeller Foundation for the contribution of many equipments used in this experiment.

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