Problem of the structural and functional organization of the immature motor center

A hypothetical structural and functional scheme of organization of the immature spinal motor center is proposed, based on our own studies carried out on rat pups of the first month of postnatal development as well as on the analysis of data from literature. Taking into account peculiarities of functioning of various chains of the segmental reflex apparatus (high excitability of the motor center, heterochrony in the development of interneurons of the spinal cord dorsal horns as well as of excitatory and inhibitory mechanisms, possibility of generation of rhythmic activity by one of the half-centers of the motor generator regardless of the activity of the other one) and the mechanisms of its cholinergic and catecholaminergic regulation, age-related changes are considered, which are connected with the organization of interrelations of elements both within the motor center and from the descending regulatory systems.     

Pattern generation

Central pattern generators are neuronal ensembles capable of producing the basic spatiotemporal patterns underlying ‘automatic’ movements (e.g. locomotion, respiration, swallowing and defense reactions), in the absence of peripheral feedback. Different experimental approaches, from classical electrophysiological and pharmacological methods to molecular and genetic ones, have been used to understand the cellular and synaptic bases of central pattern generator organization and reconfiguration of generator operation in behaviorally relevant contexts. Recently, it has been shown that the high reliability and flexibility of central pattern generators is determined by their redundant organization. Everything that is crucial for generator operation is determined by a number of complementary mechanisms acting in concert; however, various mechanisms are weighted differently in determining different aspects of central pattern generator operation.     

Cardiolipin in energy transducing membranes

Cardiolipin is a phospholipid located exclusively in energy transducing membranes such as the bacterial cytoplasmic membrane and the inner membrane of mitochondria. It plays both a structural and a functional role in many multimeric complexes associated with these membranes. The role of cardiolipin in higher order organization of components of the mitochondrial respiratory chain revealed by a combined molecular genetic and biochemical approach is described.Translated from Biokhimiya, Vol. 70, No. 2, 2005, pp. 191–196.Original Russian Text Copyright © 2005 by Mileykovskaya, Zhang, Dowhan.This revised version was published online in April 2005 with corrections to the post codes.     

Structure and Functions of Nuclear Matrix Associated Regions (S/MARs)

Modern concepts on the chromatin loop–domain organization and the role of the DNA regions specifically binding the nuclear matrix or nuclear scaffold (S/MARs) during its formation, maintenance, and regulation are discussed. Some S/MAR structural features, properties of binding the nuclear matrix, and probable mechanisms of their involvement in the gene regulation of activity are considered.     

Responses of bulbar respiratory neurons to stimulation of receptive fields in the air passages

Extracellular recordings were made of changes in the firing pattern of 74 respiratory neurons in 23 cats anesthetized with Nembutal evoked by blowing atmospheric air into the nose or through an isolated segment of trachea. Respiratory unit (RU) responses were compared with accompanying changes in the activity of inspiratory and expiratory neuromotor units (NMUs) and the intratracheal pressure. These procedures were accompanied by changes in the frequency, depth, and rhythm of respiration and RU and NMU activity was activated or inhibited; RUs of all types responded to these stimuli. Responding RUs were found in various structures of the medullary respiratory center. Most RUs responded differently to stimulation of the air passages and inflation of the lungs. It is concluded that afferent impulses from the nose and trachea spread to all groups of bulbar RUs responsible for generating respiratory movements. This wide extent of the afferent projections of the air passages in structures of the respiratory center could play an important role both in defensive respiratory responses and in the regulation of eupnea.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 3, No. 6, pp. 620–630, November–December, 1971.     

Respiratory modulation of the startle reflex in cats

Phase respiratory influences on reflex after-discharges in response to stimulation of the segmental nerves as well as tactile and acoustic stimulation in the limb and intercostal nerves — physiological analogs of startle reflexes (SR) were studied in unanesthetized (decerebrate) or chloralose-anesthetized cats. It was found that the level of these reflexes in the inhalation phase of respiration was 8–58% lower than during exhalation. The difference between the inhalation and exhalation phases was determined for different types of reflexes and under varying experimental conditions. Evidence was obtained that respiratory modulation of reflexes occurs mainly at the level of suprasegmental (reticular) mechanisms. Clear distinctions could be drawn between the pattern of reflex modulation in the lower intercostal nerves and those of the limbs. Findings would lead to the conclusion that the likely mechanisms underlying suprasegmental respiratory influences on these reflexes differ, as does the organization of their reticular centers.S. V. Kurashov Medical Institute, Ministry of Public Health of the RSFSR, Kazan'. Translated from Neirofiziologiya, Vol. 18, No. 5, pp. 593–603, September–October, 1986.     

Limb movement,intensity of integral afferent impulses from limb receptors,and level of primary afferent terminal polarization during locomotion in cats decerebrated at high level

The relationship between parameters of electrical muscle activity, changes at hindlimb joint angles, intensity of integral afferent flow, and dorsal root potential during real-life locomotion was investigated in cats decerebrated at high level. Characteristics of rear limb movements before and after deafferentation were described. It was found that afferent activity during locomotion motion consists, of two components — a tonic and a periodic phasic stage. Three main waves may be distinguished in the latter, each of which gives rise to associated changes in the level of primary afferent terminal polarization. These changes in turn are summated with the effects produced by the central generator. Correlations, between the parameters of these processes were investigated and the mechanisms underlying afferent control of locomotion generator function discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 20, No. 1, pp. 119–127, January–February, 1988.     

Possible organization pattern of interaction between the generators of cyclic motor activity and inputs from supraspinal and afferent systems

Possible organization patterns of scratching and locomotor generators that allow interpretation of experimentally demonstrated reorganizations in temporal parameters of these generator activities after electrical stimulation of descending and peripheral afferent systems were analyzed with application of mathematical simulation of neuronal generator systems. The results obtained led to the conclusion that patterns of such reorganizations influenced by signals from suprasegmental and/or peripheral systems may be determined by only two factors: 1) the structure of synaptic connections between interneuronal functional groups underlying these generator associations, and 2) the structure of connections between these groups of interneurons and fibers from suprasegmental and peripheral afferent sources. The existence of inhibitory-excitatory actions from descending and afferent systems upon the neurons of locomotor or scratching generator half-centers is a sufficient condition to ensure phasic changes in the sensitivity of these generators to supraspinal and afferent signals. The locomotor generator, unlike the scratching generator, is apparently characterized by a more complex organization of connections between functional neuronal groupings and descending fibers.Translated from Neirofiziologiya, Vol. 25, No. 1, pp. 45–50, January–February, 1993.     

Two types of P neurons in the medullary dorsal respiratory cellular group in cats

Electrophysiological properties of P neurons localized in the medullary dorsal respiratory cellular group and of vagal afferent fibers innervating these neurons were studied in acute experiments on nembutal-anesthetized cats with preserved spontaneous respiration. P neurons were shown to form a non-homogeneous cellular population. They generated phasic discharges during the whole inspiration period, but differed in their responses to lung inflation. These findings allowed us to classify P neurons as slowly adapting and rapidly adapting units, probably activated by slowly and rapidly adapting pulmonary receptors, respectively. Sensitivity of the slowly adapting P neurons to activation by the corresponding receptors and the mechanisms underlying the participation of the two types of P neurons in the reflex feedback between the respiratory center and lungs are discussed.Neirofiziologiya/Neurophysiology, Vol. 26, No. 3, pp. 211–217, May–June, 1994.     

Respiratory activity generated by semi-isolated medullo-spinal preparation and recorded from the phrenic nerve of newborn rats

Inspiratory activity generated by superfusedin situ semi-isolated medullo-spinal preparations of newborn (one-day-old) and four- to five-day-old rats was recorded from then. phrenicus before and after transverse sectioning of the ventrolateral part of the medulla (VLPM) at different levels. Under similar experimental conditions, the frequency of inspiratory discharges (ID) and their integral intensity, reflecting the volume and temporal parameters of inspiration, are much lower in one-day-old rats, as compared with those in four- to five-day-old animals. Specific roles of different VLPM levels in respiration control in young rats are demonstrated. Transection of the VLPM below the most rostral VLPM portion, corresponding to theM chemosensitive zone, caused a significant increase in the ID frequency and a decrease in the ID integral intensity. Transection performed below the intermediate VLPM region, corresponding to theS chemosensitive zone, resulted in a significant decrease in both ID frequency and ID integral intensity, up to total ID blockade in 5 of 12 1-day-old preparations. This finding can be interpreted as an indication of morphofunctional immaturity of the respiratory network in the caudal VLPM regions in newborn animals. Comparative analysis of ID pattern showed that this activity in one-day-old rats is more or less gasping-like, while that in four- to five-day-old animals is eupnoe-like. The results allow us to conclude that the level of maturity of morphofunctional organization of medullary respiratory networks considerably differs in newborn and older animals. The mechanisms responsible for formation and control of respiratory activity in early postnatal period of rats are discussed.Neirofiziologiya/Neurophysiology, Vol. 27, No. 5/6, pp. 387–395, September–December, 1995.     

Topico-anatomical relations among the structures of the caudal medullary region in early postnatal rats

Anatomical and topographical organization of the structures of the caudal medullary region was studied in 3- and 21-day-old rats. A system of stereotaxic coordinates was proposed, and brain maps for the animals of these age groups were plotted. Topographic characteristics were given for the nuclei forming the medullary respiratory center: the lateral reticular nucleus,n. ambiguus, and the nuclei of the solitary tract, vagus and hypoglossal cranial nerves. These structures differ from each other in their cytoarchitectonics and in the changes in number during their neurons' postnatal development. The differences are suggested to result from the differences in morphological maturation of the neurons at early ontogenic stages.Neirofiziologiya/Neurophysiology, Vol. 26, No. 4, pp. 243–250, July–August, 1994.     

Mitochondrial dysfunction in fibroblasts of Multiple System Atrophy

Multiple System Atrophy is a severe neurodegenerative disorder which is characterized by a variable clinical presentation and a broad neuropathological spectrum. The pathogenic mechanisms are almost completely unknown. In the present study, we established a cellular model of MSA by using fibroblasts' primary cultures and performed several experiments to investigate the causative mechanisms of the disease, with a particular focus on mitochondrial functioning.Fibroblasts' analyses (7 MSA-P, 7 MSA-C and 6 healthy controls) displayed several anomalies in patients: an impairment of respiratory chain activity, in particular for succinate Coenzyme Q reductase (p?<?0.05), and a reduction of complex II steady-state level (p?<?0.01); a reduction of Coenzyme Q10 level (p?<?0.001) and an up-regulation of some CoQ10 biosynthesis enzymes, namely COQ5 and COQ7; an impairment of mitophagy, demonstrated by a decreased reduction of mitochondrial markers after mitochondrial inner membrane depolarization (p?<?0.05); a reduced basal autophagic activity, shown by a decreased level of LC3 II (p?<?0.05); an increased mitochondrial mass in MSA-C, demonstrated by higher TOMM20 levels (p?<?0.05) and suggested by a wide analysis of mitochondrial DNA content in blood of large cohorts of patients.The present study contributes to understand the causative mechanisms of Multiple System Atrophy. In particular, the observed impairment of respiratory chain activity, mitophagy and Coenzyme Q10 biosynthesis suggests that mitochondrial dysfunction plays a crucial role in the pathogenesis of the disease. Furthermore, these findings will hopefully contribute to identify novel therapeutic targets for this still incurable disorder.     

Alterations produced in the quantitative characteristics of efferent activity parameters of the locomotor generator by decerebellation

Changes in the parameters of activity in hindlimb locomotor generators following decerebellation were quantified during experiments on decerebrate immobilized cats. Eliminating modulating cerebellar influences on nuclei of descending systems was found to lead to a slight increase in the length of activity in the flexor generator half-center and less intensive activity, as well as shortening of the period and more intensive activity in the extensor half-center, together with increased instability in generator operation, reduced statistical dependence between alterations in parameters of activity at the hindlimb half-center generators, and finally intensified effects of afferent inputs on generator activity. A comparison is drawn between the functional role of the spino-cerebellar loop in the operation of locomotor and scratch generators.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 2, pp. 142–150, March–April, 1991.     

Neuronal responses evoked in the bulbar respiratory center by stimulation of the anterior ventral and mediodorsal thalamic nuclei

The effects of rhythmical low- and high-frequency stimulation of specific nonsensory anterior ventral and associative mediodorsal thalamic nuclei (AV and MD, respectively) on the activity of neuronal units in the medullary ventral respiratory nucleus were studied in acute experiments on anesthetized, spontaneously breathing cats. Both inhibitory and excitatory influences on spike activity of inspiratory and expiratory neurons were found, with suppression effects being markedly predominant. Thresholds for inspiratory neuronal responses were lower as compared with those for expiratory cells. Electrical AV stimulation mainly produced an inhibitory effect on the activity of nonspecific reticular neurons (without respiratory activity), whereas during MD stimulation activating effects on these neurons dominated. Possible mechanisms underlying the realization of thalamorespiratory influences are discussed.Neirofiziologiya/Neurophysiology, Vol. 25, No. 3, pp. 218–223, May–June, 1993.     

Respiratory rhythm generation in rats: The importance of inhibition

Stimulation-related modifications of activity in the phrenic nerve and external and internal intercostal nerves were studied on urethane-anesthetized rats; the inspiratory medullary structures were stimulated. The activity was recorded either following microinjections of gamma-aminobutyric acid (GABA) or its derivatives into the medial parabrachial nuclei and rostral part of the ventral respiratory group of medullary neurons, or without such microinjections. Gradual dependence of activity in these nerves on the phase of the respiratory cycle was established. It was shown that the higher was the integrated inspiratory activity, the lower became the relative gain in phrenic nerve activity caused by standard stimulation. When stimulation was applied at the postinspiratory phase, the threshold stimulus intensity showed an S-like rise with an increase in integrated inspiratory activity. Microinjections of GABA or its cyclic derivatives into the parabrachial nuclear structures decreased the inhibitory effects of the latter. During the postinspiratory phase, the effect was opposite: an increase in the relative gain of inspiratory activity and drop in the threshold. The resulting data suggest that there is a two-level organization of the respiratory regulatory inhibition and that the whole respiratory neuronal network has a compartmental structure.Neirofiziologiya/Neurophysiology, Vol. 25, No. 6, pp. 420–426, November–December, 1993.     

Neuromodulation for behavior in the locust frontal ganglion

Neuromodulators orchestrate complex behavioral routines by their multiple and combined effects on the nervous system. In the desert locust, Schistocerca gregaria, frontal ganglion neurons innervate foregut dilator muscles and play a key role in the control of foregut motor patterns. To further investigate the role of the frontal ganglion in locust behavior, we currently focus on the frontal ganglion central pattern generator as a target for neuromodulation. Application of octopamine, a well-studied insect neuromodulator, generated reversible disruption of frontal ganglion rhythmic activity. The threshold for the modulatory effects of octopamine was 10^–6 mol l^–1, and 10^–4 mol l^–1 always abolished the ongoing rhythm. In contrast to this straightforward modulation, allatostatin, previously reported to be a myoinhibitor of insect gut muscles, showed complex, tri-modal, dose-dependent effects on frontal ganglion rhythmic pattern. Using a novel cross-correlation analysis technique, we show that different allatostatin concentrations have very different effects not only on cycle period but also on temporal characteristics of the rhythmic bursts of action potentials. Allatostatin also altered the frontal ganglion rhythm in vivo. The analysis technique we introduce may be instrumental in the study of not fully characterized neural circuits and their modulation. The physiological significance of our results and the role of the modulators in locust behavior are discussed.Abbreviation CPG central pattern generator - FG frontal ganglion - JH juvenile hormone - STNS stomatogastric nervous system     

Effect of a polarizing current on unit activity in the respiratory center

Single unit activity in the respiratory center in the medulla was recorded in rabbits anesthetized with urethane. The neurons were polarized through the extracellular recording microelectrode by currents of different strength and polarity. In most cases a current in the positive direction (+ to the electrode tip) increased, while a negative current decreased, the firing rate. Most indices of the firing pattern of the respiratory neurons were changed by the action of the polarizing current. The coefficient of phase shift between the pneumogram and unit activity, determined by calculating the cross-correlation function between these two processes, was the most stable index. Since it takes into account the temporal and frequency characteristics of volley activity of the respiratory neurons, this coefficient can serve as a basis for their classification. The dynamics of respiratory neuronal function under subthreshold conditions was revealed by the polarization method. It was shown, in particular, that the shape of the variable component of respiratory unit activity is close to sinusoidal and differs from that suggested by the hypothesis of reciprocal interaction between two groups of neurons.Rostov State University, Rostov-on-Don. Translated from Neirofiziologiya, Vol. 4, No. 3, pp. 280–285, May–June, 1972.     

Reordering of scratch generator efferent activity produced by stimulating hindlimb skin afferents in decerebrate immobilized cat

Reordering of the parameters of motor activity produced in the scratch generator by regular electrical stimulation of the ipsilateral hindlimb muscle nerve during different limb positions was investigated in decerebrate immobilized cats. Brief short latency inhibition of currently occurring motor activity was produced in response to stimulation, which did not cause an overall shift in the relationship between the intensity of aiming and scratching motion. Changes in cycle duration and intensity of these activities were phase-locked. Speculations were made on the functional role of the phase-locked nature of motor activity remodeling. The possible existence within the scratch generator of a model of the afferent inflow entering the spinal cord during true scratching is suggested.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 19, No. 3, pp. 382–390, May–June, 1987.     

The Respiratory Activity of Rhodococcus rhodochrousM8 Cells Producing Nitrile-Hydrolyzing Enzymes

The respiratory activity of Rhodococcus rhodochrousM8 cells containing nitrile hydratase and amidase was studied in the presence of nitriles and amides of carbonic acids. The culturing of cells with acrylonitrile and acrylamide yielding maximum respiratory activity was studied. The optimum conditions for measurements and maintenance of respiratory activity were found. Curves for the linear concentration dependence of cell respiratory activity on 0.01–0.5 mM acrylonitrile, 0.025–1.0 mM acetonitrile, and 0.01–0.1 mM acrylamide were plotted. The selectivity of cell respiratory activity for some substrates was analyzed.     

Leishmania donovani: Superoxide dismutase level in infected macrophages

Superoxide dismutase (SOD), a metal containing enzyme is present in parasiteLeishmania donovani as well as in host macrophages both resident and activated in a detectable amount, although the level is much higher in the latter case. It is observed that at any particular protein concentration, the SOD activity is highest in the case of parasite infected macrophages and lowest in the case of normal resident macrophages; the SOD activity of thioglycolate activated macrophages lies in between the two. It is also noticed that formalin-killedLeishmania donovani neither attach to macrophages nor do they increase the SOD activity of the host. Thus, the processes, e.g. attachment of the parasite to the host membrane, subsequent membrane perturbation and thus activation of membrane bound enzyme NADPH oxidase leading to respiratory burst, may be responsible for an enormous increase in the SOD level in macrophages during infection. Moreover, the chemical nature of the SOD found in infected macrophages has been investigated by using an inhibitor, e.g. NaCN, which specifically inhibits Cu–Zn SOD but not Fe–SOD. A considerable inhibition of SOD activity by NaCN in infected macrophages confirms the chemical nature of the increased SOD to be of Cu–Zn type, usually found in host. Presumably, Cu–Zn SOD or host SOD plays a protective role at the time of parasite infection although the role of parasitic SOD or some other mechanisms for the survival of the parasite within the toxic phagolysosome environment, of the macrophage cannot be ruled out.