[THE EFFECT OF MOTION SICKNESS ON THE SLEEP-WAKE CYCLE IN RATS EXPOSED TO PRENATAL HYPOXIA].

This study is a continuation of our research of phenomenology and mechanisms of motion sickness (MS) and the relation of this phenomenon to features of sleep-wake cycle (SWC) changes. It presents data about the effect of MS on SWC in 30-day-old intact rats and rats exposed previously to prenatal hypoxia on days 13 and 19 of gestation. In all groups of animals MS was shown to reduce significantly the waking time and to increase the time of paradoxical sleep (PS). For the first time it became possible to reveal a connection between hypothalamic mechanisms controlling MS and SWC and to suggest the role of this connection in mechanisms of development of the sopite syndrome which may be the only manifestation of MS in some animals and man. The results obtained demonstrate that hypoxia on day 19 of gestation has a greater damaging effect on the thalamocortical sleep-regulating structures than hypoxia on day 13 when only hypothalamic-hippocampal systems controlling slow-wave sleep were found disturbed. Against this background MS substantially suppresses the activity of the brain excitatory systems which provide wake- fulness maintenance (it appears to be the ascending reticular activating system) and enhances the work of those activating systems that control PS. It is in rats exposed to preliminary hypoxia on day 19 of gesta- tion, where it was possible to show the role of the evolutionary young thalamocortical system in the control of PS.

[BEHAVIORAL AND FUNCTIONAL VESTIBULAR DISTURBANCES AFTER SPACE FLIGHT. 2. FISHES, AMPHIBIANS AND BIRDS].

The review contains data on functional shifts in fishes, amphibians and birds caused by changes in the otolith system operation after stay under weightlessness conditions. These data are of theoretical and practical significance and are important to resolve some fundamental problems of vestibulogy. The analysis of the results of space experiments has shown that weightlessness conditions do not exert a substantial impact on formation and functional state of the otolith system in embryonic fishes, amphibians and birds developed during space flight. Weightlessness conditions do pot inhibit embryonic development of lower vertebrates but even have rather beneficial effect on it. This is consistent with conclusions concerning development of mammalian fetuses. The experimental results show that weightlessness can cause similar functional and behavioral vestibular shifts both in lower vertebrates and in mammals. For example, immediately after an orbital flight the vestibuloocular reflex in fish larvae and tadpoles (without lordosis) was stronger than in control individuals. A similar shift of the otolith reflex was observed in the majority of cosmonauts after short-term orbital flights. Immediately after landing adult terrestrial vertebrates, as well as human beings, exhibit lower activity levels, worse equilibrium and coordination of movements. Another interesting finding observed after landing of the cosmic apparatus was an unusual looping character of tadpole swimming. It is supposed that the unusual motor activity of animals as well as appearance of illusions in cosmonauts and astronauts after switching from 1 to 0 g have the same nature and are related to the change in character of otolith organs stimulation. Considering this similarity of vestibular reactions, using animals seems rather perspective. Besides it allows applying in experiments various invasive techniques.

[BEHAVIOURAL AND FUNCTIONAL VESTIBULAR DISTURBANCES AFTER SPACE FLIGHT. 1. MAMMALS].

The review contains data on functional changes in mammals caused by changes in the operation of vestibular system after space flight. These data show that the vestibular system of mammals responds to weightlessness challenge differently at various ontogenetic stages. Orbital space flight conditions have a weak effect on the developing vestibular system during embryonic period. The weightlessness conditions have rather beneficial effect on development of the fetuses. During the early postnatal period, when optimal sensory-motor tactics are created, the prolonged stay under conditions of space flight leads to development of novel, "extraterrestrial" sensory-motor programs that can be fixed in CNS, apparently, for the whole life. In adult individuals after landing essential vestibular changes and disturbances may occur that depend on the spaceflight duration. The adult organism must simultaneously solve two contradicting problems--it should adapt to weightlessness conditions, and should not adapt to them to pass the process of readaptation after returning easier. Thus, individuals must protect themselves against weightlessness influence to keep the intact initial state of health. The protection methods against weightlessness ought to be adjusted according to the duration of space flight. It should be mentioned that not all functional changes registered in adult individuals after landing can be adequately explained. Some of these changes may have chronic or even pathological character. The question of necessity to examine the influence of weightlessness on an aging (senile) organism and on its vestibular system is raised for the first time in this review. In our opinion the development of space gerontology, as a special branch of space biology and medicine, is of undoubted interest, and in the future it may be of practical importance especially taking into account the steadily growing age of cosmonauts (astronauts).

[Lateralization of behavioral reactions and otolith asymmetry].

Lateralized behavior is widely spread among vertebrate animals and is determined first of ally by structural-functional brain asymmetry as well as by the presence of somatic and visceral asymmetry. Some kinds of asymmetric reactions are suggested to be due to the presence of asymmetry at the level of sense organs, in particular, of otolith organs. This review presents data on value and character of otolith asymmetry (OA) in animals of various species and classes, on action upon it of weightlessness and hypergravity; the problem of effect of OA on vestibular and auditory functions is considered. In symmetric vertebrates, OA has been shown to be of fluctuation character and its chi coefficient varies in diapason from -0.2 to 0.2; in the overwhelmed majority of individuals, /chi/ < 0.06. The low OA level allows the paired otolith organs to work coordinately; this it why OA is at the equally low level regardless of the individual's taxonomic and ecologic position, its size, age, and otolith growth rate. Individuals with abnormally high OA level can experience difficulties in analysis of auditory and vestibular stimuli, therefore in nature the majority of such individuals are eliminated in the process of natural selection. Unlike symmetrical vertebrates, labyrinths of many Pleuronectiformes have pronounced OA--otoliths of the lower labyrinth, on a average, are significantly heavier than those of the upper labyrinth. Their organs are the only example when OA with directed character seem to play an essential role in lateralized behavior and are suggested to be used in the spatial localization of the sound source. The short-time action of weightlessness and relatively weak hypergravity (< or = 2g) do not affect OA. However, it cannot be ruled out that the long-term stay under conditions of weightlessness and hypergravity > or = 3g, as well as some diseases and shifts connected with processes of aging can enhance OA and cause several functional disturbances.

[Motion sickness in lower vertebrates: studies under conditions of weightlessness and under land conditions].

The review presents literature data and results of the author's studies with the goal to find out whether lower animals are susceptible to motion sickness. In our studies, fish and amphibians were tested for 2 h and more by using a rotating device (f = 0.24Nz, a(centrifugal) = 0.144 g) and a parallel swing (f = 0.2 Nz, a(horizontal) = 0.059 g). The performed studies did not reveal in 4 fish species and in toads any characteristic reactions of motion sickness (sopite syndrome, prodromal preparatory behavior, vomiting). At the same time, in toads characteristic stress reactions appeared (escape response, an increase in the number of urinations, inhibition of appetite), as well as some other reactions not associated with motion sickness (regular head movements, eye retraction). In trout fry this stimulation promoted dividing individuals into groups different by locomotor reaction to stress, as well as revealing individuals with a well-expressed compensatory reaction that we called the otolithotropic reaction. Analysis of results obtained by other authors confirms our conclusion. Thus, lower vertebrates, unlike mammals, are immune to motion sickness either under land conditions or under conditions of weightlessness. On the basis of available experimental data and theoretical concepts of mechanisms of motion sickness development formulated in several hypotheses (mismatch hypothesis, Traisman's hypothesis, resonance hypothesis) a synthetic hypothesis of motion sickness is presented that has the conceptual significance. According to the hypothesis, unusual stimulation producing sensomotor or senso-sensory conflict or action of vestibular and visual stimuli of about 0.2 Hz frequency is perceived by CNS as poisoning and causes corresponding reactions. The motion sickness actually is a byproduct of technical evolution. It is suggested that lower vertebrates, unlike mammals, lack a hypothetical center of subjective "nauseating" sensations; therefore they are immune to motion sickness.

Behavior of toads, Bufo bufo, in a dynamic environment.

Susceptibility to motion sickness was tested by exposing free moving toads to rotation of a stimulator modeled after an amusement park Ferris Wheel. The stimulator provided a gentle stimulation of frequency 0.25 Hz and centrifugal acceleration 0.143 g during 120 min or more without external visual cues. No emetic or prodromal behavioral response was elicited during or after rotation. During rotation the amount of motor activity in most toads increased evidently. The most active toads attempted to climb out of the test chamber. It was inferred that experimental rotation was rather a stressful stimulus which initiated an escape response. In addition, during rotation the number of eye retractions and urination incidences increased, but appetite after rotation was inhibited. During rotation the motionless toads performed small regular head movements with period equal to rotation period of stimulator. These oscillations were probably vestibular (otolith) reaction to oscillating acceleration. The proposed resonance hypothesis gives a general idea of why lower vertebrates are immune to motion sickness.

[Effect of swinging on EEG of rats of juvenile age in the wakefulness state].

Simultaneous recording of the EEG activity of superficial cortical and deep (caudate nucleus, dorsal hippocampus, anterior hypothalamus) brain parts has been performed for the first time after a 2-h swinging of frequency of 0.2 Hz in Wistar rats of juvenile age. Swinging was produced on a 4-bar parallel swing. Using a Neuron-Spectr electroencephalograph and a Diana program, normalized power spectra of wave EEG components, synchronization coefficients, and coefficients of cross-correlation between bioelectrical potentials of various brain structures were determined. After a 2-h swinging, the mean value of normalized power of slow waves of delta-diapason in hypothalamus and hippocampus was found to increase statistically significantly, while normalized power of fast waves of alpha- and beta1-diapasons in hippocampus decreased (p < 0.05). A statistically significant increase of synchronization coefficient was observed in hypothalamus and hippocampus. Changes of coefficients of cross-correlation between hypothalamus and hippocampus and other brain strictures were of the oppositely directed, individual character. In the parietal occipital brain cortex and in caudate nucleus, the changes of the EEG spectral composition also were of individual character. The obtained results on the whole correspond to data about an enhancement of the EEG low-frequency rhythms at swinging and agree with the resonance hypothesis of motion sickness.

[Behavior of trout fry Salmo gairdneri during swinging].

Ten experimental and 10 control experiments on a parallel swing and 4 experiments on a rotating stand were carried out on the fries of the trout Salmo gairdneri, strain Rofor. Depending on changes of motor activity the fish could be divided into three groups: the "freezing" fish, in which the mean swimming rate dropped sharply with the beginning of swinging; (2) the shuttle-swimming fish, in which the mean swimming rate in the process of swinging practically did not change, but which with beginning of swinging started the from-wall-towall swimming in the horizontal plane by changing direction of the movement with a frequency close to the swinging frequency; (3) the "restless" fish, in which significant fluctuations of the meanswimming rate were observed. A decrease of the motor activity in the first group fish seems to be a protective reaction. By freezing, they decrease the vestibular apparatus stimulation. Analysis of the available data allows thinking that the shuttle swimming is based on an unconditional rheoreaction characteristic of pelagic fish. Its realization during swinging depends on activity of otolith organs that until now have not been considered a possible sensor for realization of the rheoreaction. Taking into account the principal role of otoliths in this process, we called this rheoreaction variant the otolithotropic reaction. With increase of stimulus strength, the shuttle movement frequency becomes equal to the stimulation frequency. At the same time, sharpness of the otolith reaction is gradually deteriorated, which, however, is not associated with fatigue of the fish. In fish of the third group, the behavioral changes that are as pronounced as those in fish of the two former groups were not revealed. However, it is to find out the character of behavior of this fish group with increase of time and amplitude of the variable acceleration. Thus, we have managed for the first time to describe a new fish reaction to swinging--the otolith reaction and to confirm the conclusion that the swinging affects the fish motor activity. We suggest that a sharp decrease of the mean swimming rate and a disturbance of otolith reaction are signs of the fish motion sickness.

Fish otolith asymmetry: morphometry and modeling.

Mathematical modeling suggests that relatively large values of otolith mass asymmetry in fishes can alter acoustic functionality and may be responsible for abnormal fish behavior when subjected to weightlessness during parabolic or space flight [D.V. Lychakov, Y.T. Rebane, Otolith mass asymmetry in 18 species of fish and pigeon, J. Grav. Physiol. 11 (3) (2004) 17-34; D.V. Lychakov, Y.T. Rebane, Fish otolith mass asymmetry: morphometry and influence on acoustic functionality, Hear. Res. 201 (2005) 55-69]. The results of morphometric studies of otolith mass asymmetry suppose that the absolute value and the sign of the otolith mass asymmetry can change many times during the growth of individual fish within the range +/-20% [D.V. Lychakov, Y.T. Rebane, Otolith mass asymmetry in 18 species of fish and pigeon, J. Grav. Physiol. 11 (3) (2004) 17-34; D.V. Lychakov, Y.T. Rebane, Fish otolith mass asymmetry: morphometry and influence on acoustic functionality, Hear. Res. 201 (2005) 55-69]. This implies that the adverse effects of otolith asymmetry on acoustic and vestibular functionality could change during the lifetime of an individual fish. The aims of the present article were to examine the nature of otolith mass asymmetry fluctuation and to quantify otolith mass asymmetry in a large number of teleost fishes to verify our previous measurements. A dimensionless measure of otolith mass asymmetry, chi, was calculated as the difference between the masses of the right and left paired otoliths divided by average otolith mass. Saccular otolith mass asymmetry was studied in 59 Mediterranean teleost species (395 otolith pairs), 14 Black Sea teleost species (42 otolith pairs), red drum (196 otolith pairs) and guppy (30 otolith pairs). Utricular otolith mass asymmetry was studied in carp (103 otolith pairs) and goldfish (45 otolith pairs). In accordance with our previous results the value of chi did not depend on fish size (length or mass), systematic or ecological position of the fish, or otolith growth rate. In the great majority of the fishes studied, the saccular otolith chi was small /chi/ <0.05 (or <5%). Mathematical modeling indicates that values of chi vary among individual fish, but that the value is probably stable during a fish's lifetime.

Fish otolith mass asymmetry: morphometry and influence on acoustic functionality.

The role of the fish otolith mass asymmetry in acoustic functionality is studied. The saccular, lagenar and utricular otoliths are weighted in two species of the Black Sea rays, 15 species of the Black Sea teleost fish and guppy fish. The dimensionless otolith mass asymmetry chi is calculated as ratio of the difference between masses of the right and left paired otoliths to average otolith mass. In the most fish studied the otolith mass asymmetry is within the range of -0.2 < chi < +0.2 (< 20%). We do not find specific fish species with extremely large or extremely small otolith asymmetry. The large otoliths do not belong solely to any particular side, left or right. The heavier otoliths of different otolithic organs can be located in different labyrinths. No relationship has been found between the magnitude of the otolith mass asymmetry and the length (mass, age) of the animal. The suggested fluctuation model of the otolith growth can interpret these results. The model supposes that the otolith growth rate varies slightly hither and thither during lifetime of the individual fish. Therefore, the sign of the relative otolith mass asymmetry can change several times in the process of the individual fish growth but within the range outlined above. Mathematical modeling shows that acoustic functionality (sensitivity, temporal processing, sound localization) of the fish can be disturbed by the otolith mass asymmetry. But this is valid only for the fish with largest otolith masses, characteristic of the bottom and littoral fish, and with highest otolith asymmetry. For most fish the values of otolith mass asymmetry is well below critical values. Thus, the most fish get around the troubles related to the otolith mass asymmetry. We suggest that a specific physicochemical mechanism of the paired otolith growth that maintains the otolith mass asymmetry at the lowest possible level should exist. However, the principle and details of this mechanism are still far from being understood.

Otolith regularities.

The masses and the area sizes of the otoliths for the utriculus, sacculus and lagena of 15 species of the Black Sea fish are analyzed. Morphometrical otolith regularities are derived and their functional and ecomorphological explanations are suggested. The otolith regularities are summarized in four otolith rules: (1) the masses of the otoliths gradually increase with the fish growth. (2) The mass ratio of the sacculus and utriculus or the sacculus and lagena otoliths does not change with the fish growth. (3) The ratio between the otolith area s and the otolith mass m is described by the exponential equation s=alpham(2/3). (4) The ratio between the otolith and macula sizes does not change with fish growth. Mathematical modeling of the otolith displacement responses to the acoustic and the instant force stimuli is performed. Based on the modeling the functional and ecomorphological explanations of the otolith regularities are suggested: (1) the greater the otolith mass, the higher the acoustic sensitivity at low frequencies and the sharper the frequency-response curve at its maximum. (2) The separation between maxima of the frequency-response curves for the saccular and lagenar otoliths remains virtually constant with the fish growth. (3) The bottom and littoral fish have better auditory capabilities than the pelagic fish. (4) The sensitivity to vestibular stimuli for greater otoliths is higher but the response is slower. The corresponding acceleration resolution for greater otoliths is higher and the range of accelerations in which the otolith organ can operate is narrower. (5) The relative vestibular sensitivities of the utriculus, sacculus and lagena otolith organs remain constant with fish growth. (6) The otolith organs of the bottom and littoral fish are tuned to different accelerations and possess different functional properties. The otolith organs of pelagic fish are adapted to a limited range of accelerations and are less sensitive to low accelerations as compared to the bottom and littoral fish.

[The content of electrolytes (Na, K, Ca, Mg) in vertebrate otoliths and otoconia]. / Soderzhanie élektrolitov (Na, K, Ca, Mg) v otolitakh i otokoniiakh pozvonochnykh.

Na, K, Ca and Mg concentrations have been determined in the otoliths and otoconia of the lamprey, skate, guppy and hen. Lamprey otoliths sharply differ from the otoliths and otoconia of other animals with respect to their K and Ca content. In all the animals investigated excluding lamprey, only traces of K were found. Na concentration in the otilithic apparatus of the investigated animals varies within 0.475-1.04 mM/g. Na presumably is bound to proteins of the organic matrix and plays an important role in the growth of otoliths and otoconia. Concentration of Ca in the otoliths and otoconia of all animals excluding the lamprey was equal to 9.09-9.63 mM/g: organic substances constitute 4-10 per cent of their mass. In the lamprey, Ca concentration in the otoliths was found to be 5.33 mM/g, the content of organic matter amounting to more than 40 per cent. In constantly growing otoliths of fish, concentration of Mg was significantly lower than in otoconia of fish and other animals. This is presumably due to the fact that Mg inhibits crystalline growth of calcium salts.

[The vestibular apparatus of quail embryos in an experiment on the Kosmos-1129 biosatellite]. / Issledovanie vestibuliarnogo apparata u émbrionov perepela v éksperimente na biosputnike "Kosmos-1129".

The light microscope was used to study serial sections of labyrinths of quail embryos incubated and reared during 12 d orbiting of Cosmos 1129. On recovery the embryos were aged 9, 11.5 and 12 days. No significant deviations in the development of the vestibular apparatus in flight species were noted as compared to the controls. Given this and our experimental data about in-space development of fish and amphibians we may deduce that hypo-g does not exert a noticeable altering effect on the vestibular embryogenesis. Nevertheless, it should be pointed out that in all otolith organs and semicircular channel ampules of the flight embryos cup-form neural endings innervating type I sensory cells were markedly swollen in contrast to the control. Earlier swollen cup-form nerve endings have been found in one adult rat after 7 days of space flight aboard Cosmos 1667. However, exposure in space does not bring about a substantial swelling of bud-like nerve endings which contact type II sensory cells. Thus, a conclusion may be drawn that spaceflight factors are liable to produce shifts in the type I sensory cell--cup-form nerve ending unit but they do not affect type II sensory cell--bud-like nerve ending unit to the extent when effects can be identified by light microscopy.