Kiyomi Koizumi

The role of suprachiasmatic nuclei of the hypothalamus in the production of circadian rhythm

(1) Action potentials were recorded from single neurons in suprachiasmatic nuclei of hypothalamus in urethane anesthetized male rat. The rate of firing ranged from less than 1 to over 10/sec but was generally 4-8/sec, and it varied from one cell to another in the same animal. (2) Repetitive stimulation of optic nerve or light acting on the eye augmented the activity of approximately half of the the suprachiasmatic neurons examined (67 out of 159 cells) while 37 neurons (23%) showed clear inhibition by the same stimuli. (3) Stimulation of the suprachiasmatic nuclei strongly inhibited the electrical activity of cervical sympathetic nerves. Light or optic nerve stimulation also inhibited activity of cervical sympathetic nerves. (4) The rate of discharge of suprachiasmatic nuclei showed, at times, some short duration oscillations occurring every 3-5 min, but at other times the same neuron showed a steady low frequency of firing. (5) Projection of optic nerves to the suprachiasmatic nuclei was demonstrated by anterograde migration of horseradish peroxidase placed in the vitreous body. (6) It was suggested that light excites certain groups of neurons in the suprachiasmatic nuclei which exert inhibitory action on cervical sympathetic nerve. This, in turn, caused a reduction in norepinephrine release by nerve fibers innervating the pineal and a reduction in pineal enzyme production. Thus, neurons in these nuclei contribute to the suppression of pineal enzyme production produced by light.

Effect of cardiac vagal and sympathetic nerve activity on heart rate in rhythmic fluctuations

Beat-to-beat changes observed in cardiac vagal and sympathetic nerve activity and their effects on cardiac cycle length were studied during slow wave blood pressure and heart rate fluctuations (third order rhythm) and during respiratory sinus arrhythmia. Recordings were made from both nerves simultaneously in chloralose anesthetized and artificially ventilated dogs. During slow wave fluctuations in heart rate, a linear relationship was found to exist between the number of spikes per pulse interval recorded from vagal and sympathetic nerves and the length of pulse intervals. During respiratory sinus arrhythmia the time course of rhythmic changes in nerve activity and in cardiac cycle length was analyzed. Comparison of time courses indicated that vagal discharges affected the timing of not the following beat, but the one after; while the sympathetic effect was further delayed, affecting the third beat after the discharge. Baroreceptor stimulation, which resulted in lengthening the cardiac cycle, shifted this relationship by one cycle, i.e. vagal discharges affecting the occurrence of the following beat, while sympathetic discharges affecting the beat after. These results provide evidence for the conclusion that in dogs both vagal and sympathetic nerve activity contribute to the control of cardiac cycle length, however, with different time relations and effectiveness.

Studies of antidromically identified neurosecretory cells of the hypothalamus by intracellular and extracellular recordings

1. Neurosecretory neurones in supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus of cats, anaesthetized with chloralose, and dogs, anaesthetized with Nembutal, were studied. These neurosecretory neurones were identified by action potentials evoked antidromically following stimulation of the posterior lobe of the pituitary gland. Reactions of 158 such neurones in cats and 228 in dogs were analysed.

Pattern of sympathetic discharges and their relation to baroreceptor and respiratory activities

Abstract (1) The patterns of sympathetic background discharges and sympathetic reflex responses were recorded and compared in pre- and postganglionic fibers in the white rami at T 1−2 , T 10−11 , L 1−2 , cervical sympathetic nerve, splanchnic, cardiac and renal nerves in chloralose-urethane anesthetized cats. (2) Background discharges recorded from white rami at various levels of sympathetic outflow were similar. Background discharges recorded from postganglionic fibers appeared to be much different from those of the white rami. In the postganglionic fibers there was clear arterial-pulse synchronous activity. After severance of all baroreceptor afferents, rhythmic activity was still present but it was not pulse synchronous. (3) Sympathetic reflexes evoked by stimulation of the sciatic nerve showed spinal (early) and supraspinal (late) reflex responses in white rami of T 10–11 and L 1–2 , but at the T 1–2 level and in cardiac and cervical sympathetic nerves these two reflexes could not be separated because of the small difference in their latencies. Recordings from postganglionic fibers of renal nerves generally showed supraspinal reflexes only; the spinal reflexes were small or could not be distinguished from background discharges except in a few instances. (4) Background discharges as well as the sympathetic reflexes recorded from pre- and postganglionic sympathetic fibers were strongly altered by respiratory neuron activity. They were augmented during the phases of the respiratory cycle when phrenic discharges were occuring and they were depressed during absence of phrenic discharges. (5) Activation of carotid sinus baroreceptors by distention completely inhibited both background and supraspinal reflex responses recorded from pre- and postganglionic fibers, but the spinal reflex was not affected. The degree of inhibitory effect was found to be the same in all recordings, i.e. , from the white rami of various cord levels as well as in postganglionic renal and cardiac nerves. (6) The decrease in systemic blood pressure caused by repetitive stimulation of somatic myelinated fibers at low frequency (2–5/sec) was further augmented by baroreceptor activation. The two effects summated. The pressor effects and the increased sympathetic activity evoked by high frequency stimulation of myelinated (A-) fibers, or excitation of both A- and C-fibers together, were counteracted by baroreceptor activation; augmented sympathetic discharges were completely abolished for a few seconds and a decrease in blood pressure occurred. (7) It was concluded that the modulation of sympathetic activities produced by baroreceptor afferents, by the respiratory center activity and by somatic nerve excitation through supraspinal centers are similar in all sympathetic efferents.

Activity of neurones in the paraventricular nucleus of the hypothalamus and its control

1. Activity of the paraventricular nucleus neurones was recorded by micro‐electrodes during resting conditions and while various osmotic, chemical, direct and indirect neural stimuli were applied. This activity was correlated with evidence of oxytocin release by recording milk ejection responses.

Electrical activity in the supraoptic and paraventricular nuclei associated with neurohypophysial hormone release

1. Unit recordings were made from the hypothalamus in anaesthetized male rats using steel or glass micro‐electrodes.

Autonomic consequences of kainic acid–induced limbic cortical seizures in rats: Peripheral autonomic nerve activity, acute cardiovascular changes, and death

Purpose: Autonomic consequences of seizures are common, but can be severe. We sought to define changes in autonomic activity from limbic cortical seizures and their impact on the heart.

Afferent nerve groups and sympathetic reflex pathways

Summary In chloralose-anesthetized cats, two reflex sympathetic discharges were recorded from lumbar white rami after single shock stimulation of peripheral afferent nerves: an early discharge associated with a spinal reflex pathway, and a late discharge associated with a supraspinal pathway. The following relationship between afferent fibers and reflex pathways were noted: (1) Excitation of only Group I hindlimb muscle fibers did not evoke reflex sympathetic discharges. (2) Excitation of hindlimb Group II plus fibers, or of Group Aα or Aβ hind- or forelimb cutaneous, or visceral fibers evoked only the supraspinal reflex. Beyond its threshold the late response increased with stimulus strength. (3) Stimulus strengths greater than threshold for Group III hindlimb muscle, or Group Aδ hind- or forelimb cutaneous, or visceral fibers evoked the spinal sympathetic reflex. The discharge increased with stimulus strength. (4) Supraspinal sympathetic reflexes were present in all fore- and hindlimb studies. Spinal reflexes were consistently found in hindlimb nerve studies but in only one out of four forelimb nerve studies. (5) Stimuli strong enough to excite C fibers often caused increases in the late reflex sympathetic discharge. Such increases might be due to a C-fiber activated spinal pathway reflex. (6) Strychnine or tetanic stimulation of the peripheral nerves led to increased amplitudes of both early and late sympathetic responses to succeeding single shocks. (7) Stimulation of Aα or Aβ cutaneous afferent evoked an early sympathetic reflex in chronic spinal cats. Excitation of smaller fibers increased the amplitude of this reflex but did not evoke a late reflex.

Cardiovascular reflexes and interrelationships between sympathetic and parasympathetic activity

Simultaneous recordings from vagal and sympathetic nerve fibers innervating the heart have enabled us to study relationships between activity in these two autonomic nerves. Our recent studies, as well as those of others, are reviewed with respect to tonic activity and reflex actions in these two autonomic efferents. Discharges of the two nerves in relation to blood pressure pulses and to respiratory cycles are reciprocal. During slower fluctuations of hemodynamic changes which occur spontaneously, such as during Mayer waves, a reciprocal relationship between activity in the two autonomic nerves is also observed. On the other hand, in reflex responses both reciprocal and non-reciprocal patterns of reactions produced by stimulations of the hypothalamus showed varied relationships between responses in the two autonomic outflows. The functional significance of the interrelationships of the activity pattern observed in vagal and sympathetic nerves is discussed with respect to control of cardiac functions.

Contribution of unmyelinated afferent excitation to sympathetic reflexes

Abstract In this study of autonomic response to peripheral nerve afferent fiber excitation it was found that: (1) Stimulation of sural or saphenous A- and C-fibers together produced a reflex discharge followed by a silent period and a secondary late C-fiber reflex discharge in lumbar segment white rami and in the renal nerve. (2) By use of stimuli subthreshold for C-fibers and use of anodal block of A-fibers it was possible to stimulate A- and C-fibers independently. It was found that the C-fiber stimulation was responsible for the secondary reflex and increased overall efferent fiber activity. A rise in blood pressure was thus induced. A-fiber stimulation produced an earlier response and subsequent silent period. Following A-fiber stimulation the silent periods so reduced overall sympathetic discharge that depressor reactions occurred. (3) Deafferentation of baroreceptors abolished the normally occurring pulsatile surges in efferent discharge which tended to obscure the silent period following mixed fiber and A-fiber stimulation. The silent period and depressor reaction became more evident on A-fiber stimulation. Excitation of C-fibers was clearly seen to produce no silent period and only the C-fiber reflex of relative long latency. (4) Because of the latencies of response and presence of a silent period the responses recorded in this work were considered to be mediated through the medulla and not segmental spinal reactions. It was concluded that the A-fibers activate both a central excitatory and inhibitory system but the C-fibers only the excitatory complex.