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.     

Neuronal activity in the amygdaloid structure during the sleep-wake cycle of the rat

The pattern of neuronal spike activity in the amygdaloid structure was studied in the sleep-wake cycle during experiments on unrestrained rats. It was shown that most neurons of the dorsomedial portion of the amygdala display greater spike activity during active wakefulness (80%) and paradoxical sleep (66.7%) than during slow-wave sleep. Most neurons of the basolateral amygdaloid region discharged at high frequency during active wakefulness (84.6%) and during paradoxial sleep (38.4%) compared with the frequency of firing during slow-wave sleep. Some neurons were found whose rate of discharge rose during slow-wave sleep in comparison with a similar period of paradoxical sleep (38.4%) and of active wakefulness (7.7%). Our findings show how the pattern of neuronal activity in the dosromedial and basolateral regions of the amygdaloid structure differs at various stages of the sleep-wake cycle. It is postulated that this structure serves mainly to regulate emotionally motivated processes rather than helping to govern the basic mechanisms of the sleep-wake cycle.Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 17, No. 6, pp. 747–756, November–December, 1985.     

Stereological analysis of neuron, glial and endothelial cell numbers in the human amygdaloid complex

Cell number alterations in the amygdaloid complex (AC) might coincide with neurological and psychiatric pathologies with anxiety imbalances as well as with changes in brain functionality during aging. This stereological study focused on estimating, in samples from 7 control individuals aged 20 to 75 years old, the number and density of neurons, glia and endothelial cells in the entire AC and in its 5 nuclear groups (including the basolateral (BL), corticomedial and central groups), 5 nuclei and 13 nuclear subdivisions. The volume and total cell number in these territories were determined on Nissl-stained sections with the Cavalieri principle and the optical fractionator. The AC mean volume was 956 mm(3) and mean cell numbers (x10(6)) were: 15.3 neurons, 60 glial cells and 16.8 endothelial cells. The numbers of endothelial cells and neurons were similar in each AC region and were one fourth the number of glial cells. Analysis of the influence of the individuals' age at death on volume, cell number and density in each of these 24 AC regions suggested that aging does not affect regional size or the amount of glial cells, but that neuron and endothelial cell numbers respectively tended to decrease and increase in territories such as AC or BL. These accurate stereological measures of volume and total cell numbers and densities in the AC of control individuals could serve as appropriate reference values to evaluate subtle alterations in this structure in pathological conditions.     

Effects of basolateral or corticomedial amygdaloid lesions on grooming,consummatory, and locomotor behaviours in rats

Grooming behaviour in rats was induced by limited water access and by water spray before and after corticomedial or basolateral amygdaloid lesions or control operations. Corticomedial lesions produced some attenuation of grooming induced by limited water access but increased grooming induced by water spray. Basolateral lesions did not consistently affect grooming. There was an increase in ambulation time following basolateral lesions and a relative decrease in feeding time following corticomedial lesions. There were no effects of either lesion on drinking or rearing. Detailed examination of both grooming and non-grooming behaviours provided little evidence for lesion induced disruption of response sequencing.     

Effects of basolateral amygdalar nuclei on neuronal activity in the medullary respiratory center under hypoxia conditions

The effect of stimulation of the basolateral nuclei of the amygdala (ABL) on the impulse activity of respiratory neurons (RNs) of the rat medulla and the respiratory function was studied in the norm and under conditions of oxygen deficiency. Electrical stimulation of the ABL under conditions of normal atmospheric pressure exerted ambivalent effects on bulbar RNs; both activation and inhibition of these neurons were observed, but inhibitory effects noticeably prevailed. Electrical stimulation of the ABL within an initial phase of hypobaric hypoxia corresponding to ascent to a 4,000 to 5,000 m altitude exerted mostly inhibitory effects on the RN activity (similarly to what was observed under normoxia conditions). Stimulation of these nuclei within a phase of intensive hypoxia (7,500 to 8,000 m) evoked no typical responses of such neurons against the background of hypoxic suppression of their activities. Neirofiziologiya/Neurophysiology, Vol. 38, No. 4, pp. 292–297, July–August, 2006.     

Possible mechanisms of amygdala participation in the regulation of gastric motor activity

Mechanisms of the amygdala central nucleus (CNA) influence on gastric motor reflex activity were studied in electrophysiological and neuroanatomical experiments in Wistar rats. In the anaesthetized animals, electrical stimulation of the CNA affected spontaneous gastric motility and caused inhibitory as well as excitatory changes of vagus-induced gastric relaxation. The most significant and mainly inhibitory effects were observed under the stimulation of the medial CNA. Microinjection of the anterograde tracer Phaseolus vulgaris-leucoagglutimn (PHA-L) into the different divisions of the CNA revealed direct projections from its dorso-medial portion to the gastric related area of the dorsal vagal complex. Electrical stimulation of this amygdaloid area was found to change activity of the bulbar gastric related neurons. Inhibitory and excitatory changes of their vagus-induced responses under the amigdala stimulation were manifested as a general modulation of all phases of the reaction or a selective modulation of some of them. These mechanisms may underlie the amygdalo-fugal modulation of gastric motor reflex activity.     

Comparative study of effect of cortical nucleus of amygdala and pyriform cortex on activity of bulbar respiratory neurons in cats

Comparative microelectrophysiological study of character and peculiarities of effects of the cortical nucleus of amygdala and of the periamygdalar area of pyriform cortex on impulse activity was performed on the same single functionally identified respiratory medullar neurons. A high reactivity of bulbar respiratory neurons to stimulation is established in both studied limbic structures. There is established the qualitatively different character of their response reactions at stimulation of the cortical amygdala nucleus and the periamygdalar cortex. The cortical amygdala nucleus has been shown to produce both facilitating and inhibitory effects (with predominance of the activating one) on activity of medullar respiratory neurons (without topographical orderliness). The effect of periamygdalar cortex at stimulation of various parts was characterized by topographic differentiation. The suppressing reactions of neurons in the majority of cases were recorded at stimulation of the rostral area of periamygdalar cortex, whereas the excitatory reactions-at stimulation of its caudal part. Functional organization of respiratory control of the studied limbic system structures is discussed.     

Comparative study of effects of cortical nucleus of amygdala and pyriform cortex on activity of bulbar respiratory neurons in cats

Comparative microelectrophysiological study of character and peculiarities of effects of the cortical nucleus of amygdala and of the periamygdalar area of pyriform cortex on impulse activity was performed on the same single functionally identified respiratory medullar neurons. A high reactivity of bulbar respiratory neurons on stimulation is established in both studied limbic structures. There is established the qualitatively different character of their response reactions at stimulation of the cortical amygdala nucleus and the periamygdalar cortex. The cortical amygdala nucleus has been shown to produce on the activity of medullar respiratory neurons both facilitating and inhibitory action with predominance of the activating one (without topographical orderliness). The effect of periamygdalar cortex at stimulation of various parts was characterized by topographic differentiation. The suppressing reactions of neurons in the majority of cases were recorded at stimulation of the rostral area of periamygdalar cortex, whereas the excitatory reactions--at stimulation of its caudal part. Functional organization of respiratory control of the studied limbic system structures is discussed.     

Microelectrophoretic application of metabolic modifiers of the phosphofructokinase-hexosediphosphatase-system onto various types of bulbar respiratory neurons

Three metabolic modifiers of the PFK-HDPase system were applied to bulbar respiratory neurons and, for comparison, also to unspecific cells. F-6-P did not alter the spike density of the majority of the respiratory and about half of the unspecific neurons. When responding, IE units were activated and unspecific cells were inhibited. Citrate did not alter the spike density of about half of all neurons tested. When responding, excitation prevailed in IE and E units, while unspecific cells were inhibited. AMP did not alter the spike density of the majority of the respiratory and about half of the unspecific cells. When responding, I neurons were activated, inhibition preponderated in IE units and both effects occurred in unspecific cells. The large number of zero effects suggests that the activity of only part of the cells is governed by the PFK-HDPase system.     

Parameters of discharges of respiratory neurons of the ventrolateral medullary regions in early postnatal rats

In experiments on superfusedin situ semi-isolated medullo-spinal preparations (SIMSP) of newborn (1st day of life) and 4- to 5-day-old rats, we studied the parameters of extracellularly recorded spike activity of respiratory neurons of the ventrolateral medullary regions (VLMR). In SIMSP of 4- to 5-day-old rats, the frequency of discharges of pre-inspiratory, inspiratory, and expiratory neurons is shown to be significantly higher, while the dispersion of its values is considerably lower, as compared with the corresponding values for newborn animals. In the majority of pre-inspiratory and inspiratory neurons of SIMSP of newborn rats, irregular low-frequency discharges are usually generated within the interinspiration phase. The relative intensity of suppression of discharges of pre-inspiratory and expiratory neurons within an inspiration phase is much lower in SIMSP of newborn rats, as compared with that in 4- to 5-day-old preparations. The activity of most pre-inspiratory neurons manifests a trend toward transformation from a two-phase pattern in newborn rats (with two frequency peaks, pre- and post-inspiratory) to a monophasic pattern (with one pre-inspiratory frequency peak) typical of 4- to 5-day-old animals. The effects of electrical stimulation of the site of localization of pre-inspiratory neurons showed that in SIMSP of both age groups of rats an inspiratory response could be evoked in then. phrenicus only in the case when stimulation was applied within the second half of an interinspiratory phase. Therefore, it can be supposed that the respiratory network in newborn animals is to a considerable extent immature in the morphofunctional aspect. It seems probable that in early postnatal rats pre-inspiratory neurons are involved in the medullary mechanisms foron-off switching of the inspiratory and expiratory phases.Neirofiziologiya/Neurophysiology, Vol. 28, No. 4/5, pp. 207–217, July–October, 1996.     

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 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.     

Characterization of respiratory-related neurons in the isolated brainstem of the frog

Using intra- and extracellular recording techniques we examined the spontaneous discharge and membrane properties of respiratory-related neurons in isolated brainstem preparations of the frogs Rana catesbeiana and Rana pipiens that display spontaneous respiratory related activity in vitro. We observed neurons that depolarize during the fictive lung ventilation cycle as well as neurons that depolarize during the non-lung ventilation phase. Respiratory-related neurons demonstrated significant decreases in membrane input resistance during the fictive lung ventilation cycle but showed no evidence of voltage-dependent membrane conductances activated near resting membrane potential. Furthermore, respiratory neurons showed little spike frequency adaptation, their oscillatory activity was not dissociated from the global respiratory motor output following imposed changes in membrane potential, and spontaneous fluctuations in membrane potential were not observed following reversible interruption of respiratory burst activity by application of solutions low in calcium and high in magnesium. Taken together these results suggest that bulbar respiratory neurons in the isolated frog brainstem sampled in our study do not display endogenous bursting characteristics. Rather, they are strongly influenced by synaptic input. Accepted: 20 March 1997     

Electrophysiological evaluation of the intensity of protective respiratory reflexes

The impulse activity of bulbar respiratory neurons and the electrical activity of main respiratory muscles were studied stereotaxically and electromyographically on 21 male and female cats anesthetized with pentobarbital (40 mg/kg, i.p.) during defensive respiratory (expiratory and coughing) reflexes. During stimulation of laryngopharyngeal and tracheobronchial receptors, a pronounced focus of excitation appears in the bulbar respiratory centre, its peripheral manifestation being powerful electrical activity of expiratory muscles (expiratory reflex) or of both expiratory and inspiratory muscles (coughing). Respiratory defensive reflexes are very powerful and stable and are retained in hypercapnia and hypoxia.     

The neuronal organization of the limbic (cingulo-)-visceral reflex arc

The paper summarizes new electrophysiological data concerning the structural-functional organization of the limbic cortex and role of the rostral limbic region of visceral functions. Here are presented the results of a series of electrophysiological investigation of the focus of localization in the supracallosal (area 24) and infracallosal (area 25) part of the anterior cingulate gyrus of evoked potentials of maximal amplitude and minimal latent period to stimulation of pelvic, splanchnic and sciatic nerves. It was shown that evoked potentials of maximal amplitude and minimal latent periods to stimulation of viscero-somatic nerves are recorded in the supragenual area 24 in comparison with the infragenual area 25 of the anterior limbic cortex. In a series of microelectrophysiological studies of reactions of neurons of area 24 and 25 it was established that the reactivity of neurons of area 24 is higher than that of area 25. All these data indicate to the leading role of area 24 in reception and treatment of viscero-somatic afferent signals. In series of experiments it was shown that the focus of exciting neurons, forming the descending singular-autonomic discharge is localized in the infragenual area 25 of anterior limbic cortex. In a study of the comparative characteristics of sympathetic responses in lumbar white communicating rami and parasympathetic responses in pelvic nerve it was shown that evoked potentials in pelvic nerve and white rami had the lowest threshold and shorter latency in case of stimulation of area 25. Study of characteristics of influence of dorsal (area 24) and ventral (area 25) regions of rostral limbic cortex on bioelectrical activity of two postganglionic sympathetic nerves-inferior cardiac and vertebral branches of stellate ganglion, innervating coronary vessels and vessels of anterior extremities correspondingly, showed that stimulation of ventral area 25 evoked increase of electrical activity of the two sympathetic nerves and reliable increase of systemic arterial pressure, while stimulation of dorsal area 24 evoked decrease of tonic activity of the two sympathetic nerves and reliable decrease of systemic arterial pressure. In the paper are presented also the results of microelectrophysiological investigation of peculiarities of reactions of inspiratory and expiratory neurons of bulbar respiratory center to high frequency stimulation of area 24 and 25--in case of stimulation of dorsal area 24 the prevailing effect is suppression of spike activity of neurons, of stimulation of ventral, infragenual area 25 the prevailing influence is excitatory. In another series of microelectrophysiological experiments it was shown downward blocking inhibitory influence of dorsal supragenual area 24 of anterior limbic cortex on activity of vagal viscerosensory neurons of bulbar solitary tract nucleus. It is concluded that the strictly connected one another areas 24 and 25 of limbic cortex are functionally differentiated: the infra-limbic cortex is mainly a viscero-motor cortex, while the prelimbic area 24 plays a leading role in reception and treatment of viscero-somatic afferent information.     

Convergence between influences from midbrain and bulbar locomotor sites and from an inhibitory site in neurons of the medulla

Synaptic response to regular stimulation of midbrain and bulbar locomotor sites (LS) and a pontine inhibitory site (IS) was recorded in medial and lateral bulbar neurons in cats (mesencephalic decerebellate preparation). Excitatory post-synaptic potentials (PSP) and discharges were usually noted in medial neurons; mixed PSP also occurred when stimulating the IS. Almost 50% of lateral and over 25% of medial neurons showed a change in background firing rate, failing to generate response time-locked to stimulus. Medial neurons producing a response time-locked to the stimulus showed equal sensitivity to stimulation of midbrain and bulbar LT and very little reaction to IS stimulation. Medial neurons with a response not time-locked to stimuli together with lateral neurons were most receptive to input from the bulbar LS, less sensitive to stimulation of the midbrain LS, and least responsive of all to IS stimulation. Convergence between influences from midbrain and bulbar LS was the same in neurons of all populations. The part played by different neuronal populations in initiation and cessation of locomotion is discussed.Institute for Research into Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 23, No. 3, pp. 297–306, May–June, 1991.     

Response of respiratory neurons of the medulla oblongata to the septum stimulation in hypoxia

In the oxygen deficiency conditions, we studied influence of irritation of ventral (BNST), lateral (LSN) and medial (MSN) nuclei of the septum on the impulse activity of the bulbar respiratory neurons and on respiration. Phases of hypoxia were the model of experiment. In conditions of normal atmospheric pressure, the electrical stimulation of BNST, LSN and MSN nuclei of the septum exerted inhibiting as well as activating influence with the inhibiting influence prevailing. In difficult conditions of hypoxia (7.5-8 thousand meters) on the reduction of the impulse activity of neurons, stimulation of septum nucleuses induced uncharacteristic reactions of those neurons.     

Responses of bulbospinal and laryngeal respiratory neurons to hypercapnia and hypoxia

The purpose was to evaluate activities of medullary respiratory neurons during equivalent changes in phrenic discharge resulting from hypercapnia and hypoxia. Decerebrate, cerebellectomized, paralyzed, and ventilated cats were used. Vagi were sectioned at left midcervical and right intrathoracic levels caudal to the origin of right recurrent laryngeal nerve. Activities of phrenic nerve and single respiratory neurons were monitored. Neurons exhibiting antidromic action potentials following stimulations of the spinal cord and recurrent laryngeal nerve were designated, respectively, bulbospinal or laryngeal. The remaining neurons were not antidromically activated. Hypercapnia caused significant augmentations of discharge frequencies for all neuronal groups. Many of these neurons had no change or declines of activity in hypoxia. We conclude that central chemoreceptor afferent influences are ubiquitous, but excitatory influences from carotid chemoreceptors are more limited in distribution among medullary respiratory neurons. Hypoxia will increase activities of neurons that receive sufficient excitatory peripheral chemoreceptor afferents to overcome direct depression by brain stem hypoxia. The possibility that responses of respiratory muscles to hypoxia are programmed within the medulla is discussed.     

Non-participation of bulbar inspiratory neurons in the esophago-diaphragmatic inhibitory reflex

The effects of the distension of the lower oesophageal sphincter were studied on the inspiratory activity of 96 medullary neurons located either in the dorsal or in the ventral respiratory groups and on the inspiratory activity of the costal and crural parts of the diaphragm in barbiturate anaesthetized cat. Inhibition of the inspiratory activity of the crural part of the diaphragm during oesophageal distension was never associated with significant changes of the medullary inspiratory neuron discharge. These results suggest that the observed crural inhibition is due to reflex loop that does not include the inspiratory neurons belonging to the dorsal and the ventral respiratory groups.     

Participation of the cardiovascular neurons of the bulbar cardiovascular center in the adaptive reactions of the circulatory system during changes in the composition of inspired air

The experiments performed on rabbits have shown that with the inhalation of various gas mixtures the impulse activity of cardiovascular neurons in bulbar cardiovascular centre is changed. The most active are inserted cardiovascular neurons that are highly sensitive to O2 shortage and CO2 excess. It is believed that the experiments on Hering nerve severing indicate the possible development of reflex effects on hemodynamics during changes in inhaled gas composition produced from sinocarotid reflexogenic zone not only through bulbar respiratory neurons, but also through a system of inserted neurons of bulbar cardiovascular centre.