Hypothalamic TRPM8 and TRPA1 ion channel genes in the regulation of temperature homeostasis at water balance changes.

The role of the hypothalamic cold-sensitive ion channels - transient receptor potential melastatin 8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1) in homeostatic systems of thermoregulation and water-salt balance - is not clear. The interaction of homeostatic systems of thermoregulation and water-salt balance without additional temperature load did not receive due attention, too. On the models of water-balance disturbance, we tried to elucidate some aspect of these problems. Body temperature (Tbody), O2 consumption, CO2 excretion, electrical muscle activity (EMA), temperature of tail skin (Ttail), plasma osmolality, as well as gene expression of hypothalamic TRPM8 and TRPA1 have been registered in rats of 3 groups: control; water-deprived (3 days under dry-eating); and hyperhydrated (6 days without dry food, drinking liquid 4 % sucrose). No relationship was observed between plasma osmolality and gene expression of Trpm8 and Trpa1. In water-deprived rats, the constriction of skin vessels, increased fat metabolism by 10 % and increased EMA by 48 % allowed the animals to maintain Tbody unchanged. The hyperhydrated rats did not develop sufficient mechanisms, and their Tbody decreased by 0.8 °C. The development of reactions was correlated with the expression of genes of thermosensitive ion channels in the anterior hypothalamus. Ttail had a direct correlation with the expression of the Trpm8 gene, whereas EMA directly correlated with the expression of the Trpa1 gene in water-deprived group. The obtained data attract attention from the point of view of management and correction of physiological functions by modulating the ion channel gene expression.

[VESTIBULAR PROSTHETICS: CONCEPT, APPROACHES, RESULTS].

Unlike prosthetic hearing, which develops technology for more than 30 years, the problem of the vestibular prosthesis developed a little more than one and half decades. Meanwhile, the involvement of the vestibular system in ensuring the normal functioning of the visual, motor and other systems of the body determines its decisive contribution to the spatial orientation of humans and animals. In case of damage of the vestibular apparatus (the labyrinth), there are serious violations of posture control, stabilization of sight, spatial orientation, psychological status, that is, in the aggregate quality of human life deteriorates. At present, on the animals developed technology of prosthetic semicircular canals, sensing angular acceleration, and control eye movements in dynamic situations. New approaches based on the replacement of the lost natural vestibular afferent impulses by electrical stimulation through multichannel vestibular prosthesis, are successfully introducing into the clinic.

Metabotropic glutamate receptors as targets of neuromodulatory influence of nitric oxide.

A possible effect of nitric oxide (NO) on metabotropic glutamate receptor (mGluR) function in the amino acid afferent synapse was investigated in the isolated labyrinth of the frog Rana temporaria. The modification of the amplitude of responses of metabotropic glutamate receptor agonist trans-ACPD was analyzed during bath applied NO donor S-nitroso-N-acetyl-DL-penicillamine SNAP (0.1-100 µM) or nitric oxide synthase inhibitor L-NAME. It was shown that NO donor SNAP (1 µM) inhibited mGluR induced responses, and the inhibitor of NO-synthase L-NAME (100 µM) increased the amplitude of trans-ACPD evoked answers. The results suggest that NO can depress mGluR function due to modulation of functions of the endoplasmic reticulum channels.

[The effect of otolith entrances upon horizontal nystagmus induced by stimulation of semicircular ducts and retina in pigeons].

The semicircular ducts in pigeons were stimulated either in an isolated way (the angular acceleration being 10 degrees/c2) or together with the otolith organs (the peak value of the interaural acceleration being 0.5 g). In one and the same situation, both the inhibitory and the activating otolith effects on nystagmus were found. In one and the same animal, changes of the postoptokinetic and canal nystagmuses could be qualitatively different. The results obtained contradict the hypothesis of changes in the "velocity accumulator" time constants as the only cause of changes in the postoptokinetic and rotatory nystagmuses under conditions of low-frequency otolith stimulation.

[Physiology in the mirror of systematic catalogue of Russian Academy of Sciences Library].

Representation of general human and animal physiology publications in the systematic catalogue of the Library of the Russian Academy of Sciences is considered. The organization of the catalogue as applied to the problems of physiology, built on the basis of library-bibliographic classification used in the Russian universal scientific libraries is described. The card files of the systematic catalogue of the Library contain about 8 million cards. Topics that reflect the problems of general physiology contain 39 headings. For the full range of sciences including physiology the tables of general types of divisions were developed. They have been marked by indexes using lower-case letters of the Russian alphabet. For further detalizations of these indexes decimal symbols are used. The indexes are attached directly to the field of knowledge index. With the current relatively easy availability of network resources value and relevance of any catalogue are reduced. However it concerns much more journal articles, rather than reference books, proceedings of various conferences, bibliographies, personalities, and especially the monographs contained in the systematic catalogue. The card systematic catalogue of the Library remains an important source of information on general physiology issues, as well as its magistral narrower sections.

[The effect of lateral inclinations upon optokinetic and postoptokinetic nystagmus in pigeons].

Optokinetic stimulation with the angle velocity 10 degrees/s was carried out in pigeons in differently bent postures. No difference in effects of dynamic and static inclinations upon optokinetic and postoptokinetic nystagmus was found. Neither any rigid connection was found between the inclination direction and the sign of the response change. The data obtained are at variance with the hypothesis of gravity-dependent changes of the "velocity accumulator" time constant as the only cause of changes in the optokinetic and postoptokinetic responses under conditions of dynamic or static inclinations.

Artificial vestibular feedback in conditions of a modified body scheme.

Subjects standing in the dark on a rigid immobile support maintained a vertical posture, which was destabilized by vibrostimulation of both Achilles tendons. Feedback was created via the vestibular pathway using transmastoid galvanic stimulation. Changes in the current in the feedback envelope were made using a linear function based on the amplitude and rate of head displacement. Changes in the body scheme were produced using rotation of the head relative to the trunk, rotation of the trunk with the relative head position fixed, and simultaneous rotation of the head and trunk. The result of these manipulations was that the head could be rotated through essentially 90 degrees relative to the feet. In addition, rotation of one foot relative to the other through 90 degrees was used. Artificial feedback damped head oscillations induced by vibration, but only those in the vertical plane passing through the interaural axis of the head. It is suggested that changes in the vectorial characteristics of vestibular responses and the results of applying artificial feedback on the background of modified orientation of the head relative to the feet may be associated with substitution of the ensembles of vestibular hair sets providing the dominant signals in the responses of vestibulospinal neurons.

[Artificial vestibular feedback in conditions of modified body scheme].

Subjects standing in darkness on the rigid support, kept a vertical posture which was destabilized by vibration of the Achilles tendons. To create a feedback on the vestibular input, transmastoidal bipolar galvanic stimulation was used. Changes of current in the feedback contour looked as linear function considering amplitude and velocity of the subject's head displacements in reference to the vertical. To change the body scheme we used some posture configurations: turning of the head in relation to the trunk; turning of the trunk with the head fixed; joint turning of the head and trunk. As a result of these configurations, the head could be turned approximately at right angle in relation to the feet. In addition turning of one foot at right angle in relation to the other foot was used. Artificial feedback reduces body fluctuations caused by vibration only in the vertical plane which passes through interaural axis of the head. The authors assume that directional changes of vestibulo-motor responses and results of application of artificial feedback during changes of orientation of the head in relation to the feet can be connected to change of ensembles of vestibular hair cells, which signals dominate in responses of vestibulo-spinal neurones.

Effects of artificial feedback to the vestibular input on postural instability induced by asymmetric proprioceptive stimulation.

The subjects in this study maintained a vertical posture standing on a rigid support. Postural stability was assessed in terms of the standard deviations (sigma) from the mean amplitude of movements of the head relative to the null coordinate. Feedback at the vestibular input was created by transmastoid bipolar galvanic stimulation. Changes in the current in the feedback envelope were governed by a linear function based on the amplitude and rate of head movement. Variation in the coefficients of the feedback function could decrease the magnitude of sigma for lateral movements which were increased (compared with values in calm standing in the dark) by unilateral vibrational stimulation of the gluteus medialis muscle. These results provide evidence that "rate" and "position" information have different values for maintaining the vertical posture in different subjects. They also demonstrate the ability of the central nervous system (CNS) to reevaluate the weightings of the different types of information arriving via a single channel. These results support the hypothesis that galvanic vestibular input can provide the CNS with sufficient information relating to the current orientation of the body. This information can be used for postural stabilization.

[Decrease of the slow phase velocities of postrotatory nystagmi as a result of the otolith organs stimulation].

Intact pigeons were rotated in darkness in a horizontal plane at various orientations relative to axis of rotation, which passed between labyrinths, or was displaced relative to them. Trapezoidal (tests 1) and triangular (tests 2) rotation programs were used. In the tests 1, positive and negative angular accelerations were separated by two-minute periods of rotation with constant angular velocity. Such periods were absent in the tests 2. Results of the canal-otolith interactions in the tests 1 and 2 were different only in postrotatory nystagmi: the peak velocities of the slow phases decreased in both postrotatory nystagmi in the tests 1, but only in one of them in the tests 2. Apparently, at oppositely directed postrotatory nystagmi, decrease of peak velocities in the tests 1 is provided with different mechanisms. At one of them the decrease of nystagmus velocity reflects a result of a summation of canal and otolithic signals on the interneurones of the semicircular canal reflex arches, whereas at another one it is related with long-lasting activity imbalance of these interneurones which is supported by otolithic afferentation during rotation at constant angular velocity.

Vestibular influences on postural instability induced by movements of the visual environment and support.

Subjects were maintained in a vertical posture standing on a hard support with a limited degree of freedom in the frontal plane. The stability of the vertical posture was assessed on the basis of the standard deviations (sigma) from the mean amplitude of head oscillations (in the frontal and sagittal planes) relative to the origin of the coordinate system. Sinusoidal rotations of the optokinetic cylinder in which subjects stood, sinusoidal rotations of the support, and combination of these rotations, with phase discordance between movements of the cylinder and the support, led to increases in sigma in all subjects. Feedback via the vestibular input was created using transmastoid galvanic vestibular stimulation. Changes in the feedback current showed a linear function relating to the amplitude and speed of head movement. Introduction of variations in the feedback function could be used to decrease sigma for lateral oscillations; increases (compared with values on calm standing in the dark) resulted from the use of any of the destabilizing treatments. Changes in sigma for oscillations in the sagittal plane were not systematic.

[Influence of artificial vestibular feedback on posture instability caused by asymmetric proprioceptive stimulation].

Subjects kept a vertical posture, standing on a rigid support. Stability of a posture was estimated by the sizes of standard deviations (sigma) from average amplitudes of the subject's head fluctuation in respect to zero coordinates. To create a feedback on the vestibular input, transmastoidal bipolar galvanic stimulation was used. Changes of current in contour of feedback looked as linear function considering amplitude and velocity of the subject's head displacements. Varying the factors of feedback function, it was possible to reduce sigma for lateral sways increased (in comparison with their values at the quiet stance in the darkness) as a result of unilateral vibrating stimulation of m. gluteus medialis. The results specify inequality of "velocity" and "position" information for maintenance of vertical posture in different subjects. The results specify also the ability of the central nervous system (CNS) to revalue weights of various kinds of information entering via the same channel. The data confirm the hypothesis according to which galvanic vestibular input is capable to deliver in CNS and adequate information on the current orientation of the body. This information can be used for stabilization of a posture.

[Vestibular effects on posture instability evoked by moving visual environment and footing].

Subjects held the vertical posture standing up on hard footing, having small degree of the freedom in the frontal plane. The stability of the vertical posture has been assessed by the standard deviations (sigma) from average amplitudes of the fluctuations of the subject's head (in frontal and sagittal planes) from conditional zero. Sinusoidal rotations of optokinetic cylinder, sinusoidal rotations of the footing, and combinations of these rotations, under phase shifts between the optokinetic cylinder and the footing, caused increase of sigma. The amplitude and velocity signal of the head deviations was transformed into low galvanic current applied to the mastoids and used as the artifical vestibular biofeedback. It was possible to reduce the value of the sigma for lateral tilts (raised in comparison with their values during stance in the dark as a result of destabilizing influence), varying coefficients of the biofeedback. At the same time, appropriate fluctuations in sagittal plane were not systematic.

Habituation of horizontal nystagmus of the eyes in pigeons in conditions of alternating central and eccentric rotations.

Intact pigeons (n=19) were rotated in the dark in the horizontal plane in different orientations relative to the axis of rotation. In central (evoking habituation) rotations, the animal's head was located on the axis of rotation; in eccentric rotations, the animal's head was 0.6 m from the axis of rotation. Pigeons were subjected to series of alternating central and eccentric rotations; rotation directions were also alternated. Series consisted of 2-5 rotation using a trapezoidal program. Each stimulus evoking habituation was used no more than 14 times during the experiment. Eccentric rotations were found not to prevent the gradual decrease in the peak rates of the slow components of primary nystagmus occurring on the transition from one series of central rotations to another in 17 individuals (group 1); these were increased in two individuals (group 2). Group 1 showed direct relationships between changes in this measure of primary nystagmus, changes in the duration of nystagmus, and changes in the peak rates of secondary nystagmus. Modifications of nystagmus within series varied. When two identical stimuli did not follow immediately one after the other, the second stimulus induced the same changes in nystagmus as observed in the individual in the first and next series of central rotations. If two identical stimuli followed one immediately after the other, the second stimulus in the pair often induced increases in the peak rates of primary and secondary nystagmus, along with increases in the time taken to reach the peak rate of primary nystagmus. These changes were non-random at a probability of >95%.

[Habituation of horizontal eye nystagmus in pigeon during alternation of central and eccentric rotations]. / Gabituatsiia gorizontal'nogo nistagma glaz u golubei pri cheredovanii tsentral'nykh i ékstsentrichnykh vrashchenii.

Intact pigeons were rotated in the horizontal plane in the dark in different positions relatively to the rotation axis. At central rotations, the pigeon's head was in the rotation axis whereas at eccentric rotations it was displaced from the axis. Series of central and eccentric rotations were alternated. Each series consisted of 2-5 rotations using angular velocity trapezoids. All stimuli producing habituation were used at most 14 times each. Eccentric rotations did not prevent a gradual decrease of peak velocities of the slow component of primary nystagmus on transition from one series of central rotations to another in 17 pigeons (group 1). The increase of peak velocities was observed in 2 pigeons (group 2). In group 1, a direct dependence among alterations of this parameter of primary nystagmus, modifications of its duration, and variations of peak velocities of secondary nystagmus, were observed. If two identical stimuli did not follow in sequence directly, the effect of the second one produced same nystagmus changes as were observed in present pigeon by comparison of the first and last responses in the series of the central rotations. If they follow one by one, in many cases the second stimulus in the pair produced an increase of peak velocity of primary and secondary nystagmus and rise of delay of the point of primary nustagmus peak velocity. These variations were not random (probability, > 95%).

[Mechanisms of the otolith signal processing]. / Mekhanizmy obrabotki otolitovykh signalov.

A series of current hypotheses of mechanisms of the otolith signals processing and organization of adaptive responses of the oculomotor system to gravito-sensitive (otolith) inputs are reviewed: the "frequency segregation of the otolith signals", "gravito-inertial force resolution", "spatio-temporal transformation of the angular vestibulo-ocular reflex", "inertial processing of the vestibular signals", "asymmetry of the otolith signals", and their experimental corroboration.

Mechanisms of the interaction of the angular and linear components of the horizontal vestibulo-ocular reflex in the pigeon.

Intact pigeons (Columba livia, n = 30) were rotated in a horizontal plane in the dark at different orientations relative to the axis of rotation. A total of 24 birds showed different directions of changes in the duration of contrarotatory nystamus (on transition from central rotation to eccentric), along with displacement of the otolith membranes in both the frontal and sagittal planes. These pigeons showed a direct relationship between changes in the duration of the primary phase of nystagmus and the peak rate of the slow component on the background of increasing centrifugal force, while no such relationship was seen in conditions of decreasing centrifugal force. Increases in the duration of the primary phase were accompanied by decreases in the duration of the secondary phase (i.e., the reversive phase) and vice versa. These data provide evidence that the otolith component is not decreased to zero by rotation at constant angular rates or immediately after this stopped; in conditions of negative angular acceleration, this component was biphasic. The results are in good agreement with a hypothesis [2] suggesting that the otolith component represents asymmetric (different in paired brain structures) neuronal activity modifying the canal component even when the level of asymmetry is itself insufficient to initiate eye movements.

Fragmentary control of vestibuloocular responses.

Intact pigeons (n = 64) were rotated in the dark in the horizontal plane at different orientations relative to the axis of rotation. The overall patterns of changes in nystagmus of the eyes arising as a result of displacement of the otolith membranes in several directions were analyzed. In ten pigeons, all changes in nystagmus (type 1 general patterns) could be explained in terms of the dynamics of peripheral neuron activity and non-specific (identical for all combinations of interacting inputs) central influences. In the remaining pigeons, part of the change in nystagmus (type 2 general patterns) was associated with central influences which were not identical for different combinations of interacting inputs. Repeated unusual combinations of vestibular stimuli and subsequent treatment with Nembutal transformed type 2 general patterns into type 1 general patterns. These data provide evidence for the fragmentary control of eye movements, whereby there is selective (fragmentary) modification of only some (individually specific) combinations of canal and otolith signals out of the whole set of vestibuloocular responses arising in response to stimulation of paired vestibular inputs; modification is mediated by changes in the sign of otolith influences on the canal components of these responses.

Short-term memory processes in delayed visual differentiation in rhesus macaques after bilateral removal of field 7 of the parietal cortex.

Monkeys (Macaca mulatta) with preliminary removal of field 7 of the lower parietal cortex and previously trained to differentiate images differing in shape, color, size, orientation, and spatial relationships were used to study the processes involved in short-term storage of different types of information required for a delayed (by 0-8 sec) visual differentiation task and the effects on these processes of the antioxidant Oxymetacil. Significant differences were found in comparison with intact animals. Removal of field 7 sharply worsened short-term storage processes during visual differentiation of different types of images, including those differing in terms of properties such as color, geometrical shape, and the spatial relationships between image elements. There were significant reductions in the level of correct responses for all delay periods with significant increases in the motor reaction time, indicating a sharp reduction in the duration of short-term information storage, which suggests that the monkeys' short-term memory mechanisms were disrupted. Oxymetacil had a correcting effect only in relation to stimuli differing in terms of color and shape, but had no effect at all on the short-term storage of spatial information. It is suggested that these data suggest that field 7 has at least two functions. These are, firstly, a role in processes underlying the evaluation, differentiation, and storage of spatial information depending on visual-vestibular interactions, and secondly, a role in the mechanisms underlying the attention system, which is disrupted by removal of field 7 and restored by treatment with the antioxidant when there is no need to differentiate spatial information, a process which depends on assessment of the body image and egocentric orientation based on visual-vestibular interactions.

Relationship between learning characteristics and the properties of visual objects in rhesus macaques with bilateral removal of parietal cortex field 7.

Behavioral experiments were used in rhesus macaques with bilateral excision of field 7 of the lower parietal cortex to study the relationship between visual differentiation learning processes and a variety of stimulus properties. All animals showed significant differences associated with stimulus properties, which produced different types of learning curves. For each monkey, visual stimuli were divided into compact groups in terms of the "similarity" of their learning characteristics. Removal of field 7 had no effect on the process of learning visual image discrimination when this was based on properties such as color and geometrical shape, but worsened the learning characteristics when visual differentiation was based on spatial information, when the learning process became unstable, with increases in the numbers of peaks and troughs on the learning curve and a significant increase in the duration of the learning period. The time to a stable motor response also became significantly greater than for visual images distinguished by shape and color. It is suggested that during the process of learning visual discrimination, processing and extraction of image signs by the visual system for objects characterized by spatial relationships is accompanied by the formation of spatial distinguishing signs, this process involving neuronal structures in field 7 of the lower parietal cortex, which appears to be the main area determining visual-vestibular interactions. Increases in oscillations and in the difficulty of the learning process for differentiation on the basis of spatial information after removal of field 7 might be due to a transfer from one strategy to another, resulting from disruption of the mechanisms which evaluate body image and egocentric orientation on the basis of visual-vestibular interactions.