Genyo Mitarai

Glial Control of Neuronal Networks and Receptors

Our experimental findings which showed the glial origin of the retinal S-potentials and their behavior were for the first time presented and discussed at this symposium. The conference, concerning the same subject, given by Svaetichin (October 26, 1960) at Washington, stimulated his old friend and colleague Robert Galambos to write a paper concerning “a glia-neural theory of brain function” [Proc. Nat. Acad. Sci. 47, 129 –136 (1961)]. This exciting article is a much better introduction to our work than anything we could have written ourselves, since it emphasizes the problem faced by the conventional “millisecond” neurophysiology and the neuron theory when trying to explain complex functions of our nervous system, as for instance sleep, alertness, learning, memory, inborn instinctive behavior, etc., and also gives a historical review of earlier thought, suggesting an important role for the glia in brain function. Anatomical and biochemical studies (Nansen, Holmgren, KornmUller, Hyden, Sjostrand, DE Robertis, G. Villegas and others) suggest the existence of interactions between the neuron and the glia; however, our studies directly demonstrate that the glial cells exert a metabolic excitability control on the neurons. Actually, all investigations on the S-potentials which have been carried out since 1953 are studies on the functional mechanisms of the glial cells, although this had not been realized before we definitely localized the recording site of the micro-electrode to individual Muller fibers and (glial) horizontal cells of the Teleost retina.

Glia-Neuron Interactions and Adaptational Mechanisms of the Retina

The graded electrical response ( S-potential) recorded intracellularly from the fish retina (28, 29) has been found to originate in two different types of glial cells: (a) the L-type from the horizontal cell; and (b) the C-type from the Muller fiber (33). Our theory of neuron-glia interaction leads us to believe that the S-potentials reflect the metabolic processes taking place in the glial cells, the glial function being intimately coupled with the activity of the neurons and receptors, on which components the glial cells exert a metabolic excitability control.

A comparative study of membrane potential changes in neurons and neuroglial cells during spreading depression in the rabbit

Abstract (1) Both glial and neuronal depolarizations during SD were recorded on the sensorimotor cortex of the rabbit. Glial depolarizations were monophasic and sigmoidal. Neuronal depolarizations could be divided into two stages: an earlier rapid depolarization phase with burst discharges and a later gradual phase with no spike. (2) Average amplitudes of depolarizations with glial cells and neurons were almost the same, 32 and 33 mV, respectively. The average membrane levels observed at maximal depolarizations were relatively constant, −33 mV for glial cells and −16 mV for neurons. (3) Taking into account the extracellular field potentials, it is therefore highly probable that neurons depolarize more than glial cells and can even assume a positive intracellular potential. (4) The correlation of initial membrane potential and amplitude of depolarization in glial cells (correlation coefficient, 0.93) was much closer than in neurons (0.63). (5) Individual intracellular potential changes of neurons and glial cells could be superimposed to form a laminar profile, when adjusted in the horizontal plane at their average maximal levels in membrane depolarization.

The Effect of Temperature, Carbon Dioxide and Ammonia on the Neuron-Glia Unit

The intra-cellular origins of the luminosity and chromatic S-potentials have been located (8), by means of glass micro-electrodes containing a lithium carmine solution. Since the responses were found to originate in glial structures (horizontal cells and Muller fibers respectively), they were considered to be extra-neuronal correlates of the processes occurring in the nerve cells. This induced our group to examine as far as possible the relations between the glial and the neuronal behavior, and it has now become clear to us that the glial cells are definitely involved in the control of excitability in the nervous system.

Discrete nonlinear reduction model for horizontal cell response in the carp retina

In this paper we present a new model for the spatial behavior of the external horizontal cells in the carp retina which elucidates more precisely the mechanisms of their intercellular connections. The area and intensity effects of a brief light stimulus on the L-type response were recorded and analysed. We discovered clear nonlinearities in the behavior of the response which could not be explained by the simple summative model presently accepted. Proposed here is a new model, the spatial reduction mechanism, which explains the experimental evidences including these nonlinearities. We also present the results of a computer simulation using our new model in parallel with the actual results obtained experimentally. The physiological implications of these findings are discussed.

Enhanced Hoffman-reflex in human soleus muscle during exposure to microgravity environment

Responses of Hoffman-reflex in the soleus muscle to changes of gravity levels created by parabolic flight of a jet airplane were investigated in four healthy male subjects. The subjects maintained a sitting position with seat belts fastened, keeping the anterior ankle and posterior knee angles at approximately 135 degrees. The gravity levels were altered from 1- to 2-G, and then microgravity was created for approximately 20 s. The levels were recovered from 1.5- to 1-G during the descending phase. The time interval between the stimulation and either M- or H-wave was not influenced by the changes in gravity levels. The amplitude of the M-wave during hyper- and microgravity was identical to that obtained at 1-G. However, the H-wave amplitude was increased when the subjects were exposed to microgravity (approximately four times vs. 1-G level). The H/M ratio was also elevated during microgravity. Further, such a phenomenon was maintained throughout the 20 s of microgravity exposure. Hypergravity at 1.5- or 2-G had no effect on the H-wave amplitude. It is suggested that an acute exposure to microgravity increases the excitability of the soleus motor pool and the increased excitability is restored immediately when the gravity level is elevated.

Space experiment using large-sized fish: In case of carp in Spacelab-J mission

Two carp of 26 cm in size, intact and otolith-removed (LB), were flown on the Spacelab-J for 8 days in September 12-20, 1992. Light-dependent reaction to alternating direction of illumination was recorded for 10 min twice a day together with the cerebellar EEG activity, on 2 days before the launch, during the flight and for 4 days after the landing, in same fish chamber. Reproducing the video image, it was revealed that both carp were healthy during the mission, but the LB fish was almost immobilized from the 3rd test session (48 hours in flight) by tight twisting of the EEG cable. Both fish after landing tended to stay still on the bottom of the fish chamber. Findings that the body weight reduced remarkably in both fish and that nitrite and nitrate levels of the fish water were usually high, suggested that the fish metabolism might have been enhanced during the flight.

Spreading depression in isolated carp retina

(1) Spreading depression (SD) could be elicited in isolated carp retina by KCI application, the concomitants of which were similar to those described in other vertebrates. (2) The threshold for generating SD was greatly reduced by brief immersion of the retina in low ci-ringers solutions. The properties of SD waves were almost the same with treated and untreated retinas, except for intervals. (3) Extracellular negative potential shifts during SD, averaging 4.6 mV in amplitude and 27 sec in duration, were recorded in whole retinal layers with the maximum amplitude about at the inner plexiform layer. (4) The PIII potential of the local electroretinogram was virtually unaffected by SD. (5) Both L-and C-type S-potentials could be evoked with increase of 20-40% in amplitude around the peak of slow membrane depolarizations (mean value of maximal amplitude 5.8 mV) during SD in horizontal cells. (6) Increase in spike number was observed in both on-and off-center ganglion cells before and after the spike cessation during SD in the untreated retina. However, the off-discharges, which were a unique response to light in the immersed retina, only decreased during SD.

Electroencephalographic analysis of activities in the optic tectum of unrestrained carp

Electroencephalographic activity of the optic tectum in unrestrained resting carp was classified into three dominant frequency ranges of 4-7, 8-13 and 14-25 HZ, peaking at 6, 10, and 17 and 22 HZ, respectively, under power spectral analysis. All these activities were suppressed in the dark. The suppression was most prominent in the 8-13 HZ waves, but less so in the 4-7 HZ. However, while the fish was swimming actively, the 4-7 HZ spectrum increased in power and no actual increase could be observed for the higher frequency waves. Thus, it is probable that the 4-7 HZ waves involve rich motor activity, while the 8-13 HZ waves are mainly visual. The tectal activity was enhanced in the hypoxic state, with an increase in all frequency components, and enhanced further after loading, each of which corresponds to the hypoxic and post-hypoxic activations described for the mammalian cortex. A component analysis for the photically evoked response in restrained carp supported the four peaks of fundamental tectal rhythm being obtained as the spontaneous activity. In addition, each component belonging to the lower two peaks could be decomposed into the others, suggesting that the 17 and 22 HZ waves might be elementary for the tectal activity.

Correlation between vestibular sensitization and leg muscle relaxation under weightlessness simulated by water immersion

The experiments were designed to determine the contribution of the leg muscle relaxation to the sensitization of the vestibular function under weightlessness, The neuromuscular unit (NMU) discharges were continuously recorded with microelectrodes from the anti-gravitational soleus muscle and its antagonist, the tibialis anterior, of a man standing first upright on the level floor of a dry water tank, and then gradually being immersed in water till it reached his neck; while he was buoyed with an airtube placed under his armpit. In each of the successive states, the caloric nystagmus was evoked, analyzed and compared with the NMU discharge as well as with subjective symptoms associated with the nystagmus. The results indicate that the nystagmogenic activity had a significant correlation with the appearance of the active NMU in the soleus, and they also suggest that the reduction of ascending signals from the antigravity muscles might be one of the causes of atypical vestibular responses occuring in weightlessness.