Influence of respiratory network drive on phrenic motor output evoked by activation of cat pre-Botzinger complex

We have previously demonstrated that microinjection of dl-homocysteic acid (DLH), a glutamate analog, into the pre-B?tzinger complex (pre-B?tC) can produce either phasic or tonic excitation of phrenic nerve discharge during hyperoxic normocapnia. Breathing, however, is influenced by input from both central and peripheral chemoreceptor activation. This influence of increased respiratory network drive on pre-B?tC-induced modulation of phrenic motor output is unclear. Therefore, these experiments were designed to examine the effects of chemical stimulation of neurons (DLH; 10 mM; 10-20 nl) in the pre-B?tC during hyperoxic modulation of CO2 (i.e., hypercapnia and hypocapnia) and during normocapnic hypoxia in chloralose-anesthetized, vagotomized, mechanically ventilated cats. For these experiments, sites were selected in which unilateral microinjection of DLH into the pre-B?tC during baseline conditions of hyperoxic normocapnia [arterial PCO2 (PaCO2) = 37-43 mmHg; n = 22] produced a tonic (nonphasic) excitation of phrenic nerve discharge. During hypercapnia (PaCO2 = 59.7 +/- 2.8 mmHg; n = 17), similar microinjection produced excitation in which phasic respiratory bursts were superimposed on varying levels of tonic discharge. These DLH-induced phasic respiratory bursts had an increased frequency compared with the preinjection baseline frequency (P < 0.01). In contrast, during hypocapnia (PaCO2 = 29.4 +/- 1.5 mmHg; n = 11), microinjection of DLH produced nonphasic tonic excitation of phrenic nerve discharge that was less robust than the initial (normocapnic) response (i.e., decreased amplitude). During normocapnic hypoxia (PaCO2 = 38.5 +/- 3.7; arterial Po2 = 38.4 +/- 4.4; n = 8) microinjection of DLH produced phrenic excitation similar to that seen during hypercapnia (i.e., increased frequency of phasic respiratory bursts superimposed on tonic discharge). These findings demonstrate that phrenic motor activity evoked by chemical stimulation of the pre-B?tC is influenced by and integrates with modulation of respiratory network drive mediated by input from central and peripheral chemoreceptors.     

Interrelations of the Autogenic Somatomotor Excitation of the Cardiac Activity in Developing Rats

In developing rats aged from newborns to 1.5 months, regularities were studied of the heart rate fluctuations associated with periodic bursts of the endogenous somatomotor excitation characteristic of early stages of postnatal ontogenesis of immature born animals. It has been established that decelerations predominate on the background of the motor bursts for the first week of life, whereas accelerations, since the beginning of the 3rd week. The heart rhythm changes can precede or lag behind the beginning of the motor excitation, which allows judging about the existence of two mechanisms of the interaction: about the heart reaction to motor activity and about the central drivers acting simultaneously on the both systems. Experiments with chronic desympathization and block of -adrenoreceptors indicate a participation of the sympathetic nervous system in formation of the motor-cardiac interaction.     

An endogenous motor program for sand crab uropods.

A stereotyped pattern of spontaneous, rhythmic bursting in motoneurons of three principal uropod muscles in the sand carb Emerita analoga has been recorded from a deafferented chain of the four most-posterior abdominal ganglia. This endogenous motor program resembles the electromyogram pattern recorded from return-stroke and power-stroke muscles in swimming crabs in that (1) latencies of power-stroke bursts and burst periods are positively correlated with each other and (2) durations of power-stroke bursts are brief and nearly invarient. The endogenous program differs from the electromyogram pattern in having longer periods and return-stroke bursts which are brief and sporadic. The neural oscillator underlying the endogenous motor program, therefore, appears to drive the power stroke. Circumstantial evidence suggests that it may also inhibit return stroke motoneurons concurrently with excitation of the power-stroke excitor.     

An endogenous motor program for sand crab uropods

A stereotyped pattern of spontaneous, rhythmic bursting in motoneurons of three prinicipal uropod muscles in the sand crab Emerita analoga has been recorded from a deafferented chain of the foru most-posterior abdominal ganglia. This endogenous motor program resembles the electromyogram pattern recorded from return-stroke and power-stroke muscles in swimming crabs in that (1) latencies of power-stroke bursts and burst periods are positively correlated with each other and (2) durations of power-stroke bursts are brief and mearly invarient. The endogenous program differs from the electromyogram pattern in having longer periods and return-stroke bursts which are brief and sporadic. The neural oscillator underlying the endogenous motor program, therefore, appears to drive the power stroke. Circumstantial evidence suggests that it may also inhibit return-stroke motoneurons concurrently with excitation of the power-stroke excitor.     

Focal CO2/H+ alters phrenic motor output response to chemical stimulation of cat pre-Botzinger complex in vivo.

Microinjection of dl-homocysteic acid (DLH), a glutamate analog, into the pre-B?tzinger complex (pre-B?tC) can produce tonic excitation of phrenic nerve discharge. Although this DLH-induced tonic excitation can be modified by systemic hypercapnia, the role of focal increases in pre-B?tC CO(2)/H(+) in this modulation of the DLH-induced response remains to be determined. Therefore, we examined the effects of unilateral microinjection of DLH (10 mM; 10-20 nl) into the pre-B?tC before and during increased focal pre-B?tC CO(2)/H(+) (i.e., focal tissue acidosis) in chloralose-anesthetized, vagotomized, mechanically ventilated cats. Focal tissue acidosis was produced by blockade of carbonic anhydrase with either focal acetazolamide (AZ) or methazolamide (MZ) microinjection. For these experiments, sites were selected in which unilateral microinjection of DLH into the pre-B?tC produced a nonphasic tonic excitation of phrenic nerve discharge (n = 10). Microinjection of 10-20 nl AZ (50 microM) or MZ (50 microM) into these 10 sites in the pre-B?tC increased the amplitude and/or frequency of eupneic phrenic bursts, as previously reported. Subsequent microinjection of DLH produced excitation in which phasic respiratory bursts were superimposed on tonic discharge. These DLH-induced phasic respiratory bursts had an increased frequency compared with the preinjection baseline frequency (P < 0.05). These findings demonstrate that modulation of phrenic motor activity evoked by DLH-induced activation of the pre-B?tC is influenced by focal CO(2)/H(+) chemosensitivity in this region. Furthermore, these findings suggest that focal increases in pre-B?tC CO(2)/H(+) may have contributed to the modulation of the DLH-induced responses previously observed during systemic hypercapnia.     

Characteristics of autogenic motor stimulation in rat pups

Studies have been made on the organization of the spontaneous motor activity during first 2 weeks of postnatal life of rats Rattus norvegicus (var albin.) by means of prolonged EMG recording from the gastrocnemius muscle and by computer analysis. Complexes of prolonged activity with a period of about 1 min, intracomplex periodicity of short pulses with a frequency 1/sec and periodicity of separate short bursts arranged into series with intervals between them of approximately 8-12 sec were observed. It was found that the main rhythm of these forms of excitation remains relatively unchanged during postnatal ontogenesis. The number of periods filled by series of short bursts decreases in postnatal development of animals, whereas the number of periods of a complete rest lasting for 1 1/2 and more minutes increases. These findings were compared with the development of sleep--wakefulness cycle in early postnatal ontogenesis.     

Formation of cardiomotor interrelations in rat ontogenesis

Age-related transformations and nature of short-term positive and negative oscillations of cardiac contraction rhythm were studied in comparison with periodical spontaneous somatomotor activity bursts in rats for the first 3 weeks after birth. It has been established that both accelerations and decelerations can be independent, precede motor excitation or appear as a consequence of muscle contraction. The main role in genesis of decelerations is played by parasympathetic mechanisms whose action is blocked by atropine. Activation of vagus cardiomotor centers can ether occur spontaneously by producing independent declerations or appear as reaction to motor excitation. Genesis of accelerations is connected with activity of sympathetic nervous system, as they are inhibited under conditions of desympathization or block of adrenoreceptors. The main role in realization of accelerations is played by somatosympathetic reflex, but connection with motor activity can also be effected by the principle of pre-tuning to expected movement.     

Chemical activation of pre-Bötzinger complex in vivo reduces respiratory network complexity

In the in vivo anesthetized adult cat model, multiple patterns of inspiratory motor discharge have been recorded in response to chemical stimulation and focal hypoxia of the pre-B?tzinger complex (pre-B?tC), suggesting that this region may participate in the generation of complex respiratory dynamics. The complexity of a signal can be quantified using approximate entropy (ApEn) and multiscale entropy (MSEn) methods, both of which measure the regularity (orderliness) in a time series, with the latter method taking into consideration temporal fluctuations in the underlying dynamics. The current investigation was undertaken to examine the effects of pre-B?tC-induced excitation of phasic phrenic nerve discharge, which is characterized by high-amplitude, rapid-rate-of-rise, short-duration bursts, on the complexity of the central inspiratory neural controller in the vagotomized, chloralose-anesthetized adult cat model. To assess inspiratory neural network complexity, we calculated the ApEn and MSEn of phrenic nerve bursts during eupneic (basal) discharge and during pre-B?tC-induced excitation of phasic inspiratory bursts. Chemical stimulation of the pre-B?tC using DL-homocysteic acid (DLH; 10 mM; 10-20 nl; n=10) significantly reduced the ApEn from 0.982+/-0.066 (mean+/-SE) to 0.664+/-0.067 (P<0.001) followed by recovery ( approximately 1-2 min after DLH) of the ApEn to 1.014+/-0.067; a slightly enhanced magnitude reduction in MSEn was observed. Focal pre-B?tC hypoxia (induced by sodium cyanide; NaCN; 1 mM; 20 nl; n=2) also elicited a reduction in both ApEn and MSEn, similar to those observed for the DLH-induced response. These observations demonstrate that activation of the pre-B?tC reduces inspiratory network complexity, suggesting a role for the pre-B?tC in regulation of complex respiratory dynamics.     

Temporally patterned activity recorded from mandibular nerves of the isolated subesophageal ganglion of Manduca

We recorded bursts of motor neuron activity from closer and opener mandibular nerves of isolated subesophageal ganglia (SOG) and compared them with the feeding motor pattern of intact Manduca larvae. Closer bursts recorded from isolated SOG lasted from 1 to 4s, interburst interval durations lasted from 2 to 49s, and within- and between-animal variability was great. In contrast, motor activity bursts (EMGs) measured from mandibular closer muscles of intact, feeding animals lasted 0.08 to 0.24s with interburst intervals of 0.26 to 0.57s. Variability both within and between animals was small. Bath application of 10(-4)M octopamine to the isolated SOG tended to increase frequency and reduce the duration of bursts, so that they became more like those recorded during feeding.     

Sub-MHz bursts of nanosecond pulses excite neurons at paradoxically low electric field thresholds without membrane damage

Neuromodulation applications of nanosecond electric pulses (nsEP) are hindered by their low potency to elicit action potentials in neurons. Excitation by a single nsEP requires a strong electric field which injures neurons by electroporation. We bypassed the high electric field requirement by replacing single nsEP stimuli with high-frequency brief nsEP bursts. In hippocampal neurons, excitation thresholds progressively decreased at nsEP frequencies above 20–200 kHz, with up to 20–30-fold reduction at sub-MHz and MHz rates. For a fixed burst duration, thresholds were determined by the duty cycle, irrespective of the specific nsEP duration, rate, or number of pulses per burst. For 100-μs bursts of 100-, 400-, or 800-ns pulses, the threshold decreased as a power function when the duty cycle exceeded 3–5 %. nsEP bursts were compared with single “long” pulses whose duration and amplitude matched the duration and the time-average amplitude of the burst. Such pulses deliver the same electric charge as bursts, within the same time interval. High-frequency nsEP bursts excited neurons at the time-average electric field 2–3 times below the threshold for a single long pulse. For example, the excitation threshold of 139 ± 14 V/cm for a single 100-μs pulse decreased to 57 ± 8 V/cm for a 100-μs burst of 100-ns, 0.25-MHz pulses (p < 0.001). Applying nsEP in bursts reduced or prevented the loss of excitability in multiple stimulation attempts. Stimulation by high-frequency nsEP bursts is a powerful novel approach to excite neurons at paradoxically low electric charge while also avoiding the electroporative membrane damage.     

Multiple neural oscillators and muscle feedback are required for the intestinal fed state motor program

After a meal, the gastrointestinal tract exhibits a set of behaviours known as the fed state. A major feature of the fed state is a little understood motor pattern known as segmentation, which is essential for digestion and nutrient absorption. Segmentation manifests as rhythmic local constrictions that do not propagate along the intestine. In guinea-pig jejunum in vitro segmentation constrictions occur in short bursts together with other motor patterns in episodes of activity lasting 40-60 s and separated by quiescent episodes lasting 40-200 s. This activity is induced by luminal nutrients and abolished by blocking activity in the enteric nervous system (ENS). We investigated the enteric circuits that regulate segmentation focusing on a central feature of the ENS: a recurrent excitatory network of intrinsic sensory neurons (ISNs) which are characterized by prolonged after-hyperpolarizing potentials (AHPs) following their action potentials. We first examined the effects of depressing AHPs with blockers of the underlying channels (TRAM-34 and clotrimazole) on motor patterns induced in guinea-pig jejunum, in vitro, by luminal decanoic acid. Contractile episode durations increased markedly, but the frequency and number of constrictions within segmenting bursts and quiescent period durations were unaffected. We used these observations to develop a computational model of activity in ISNs, excitatory and inhibitory motor neurons and the muscle. The model predicted that: i) feedback to ISNs from contractions in the circular muscle is required to produce alternating activity and quiescence with the right durations; ii) transmission from ISNs to excitatory motor neurons is via fast excitatory synaptic potentials (EPSPs) and to inhibitory motor neurons via slow EPSPs. We conclude that two rhythm generators regulate segmentation: one drives contractions within segmentation bursts, the other the occurrence of bursts. The latter depends on AHPs in ISNs and feedback to these neurons from contraction of the circular muscle.     

Spontaneous and evoked activities of interpositus nucleus neurons before and after lesion of the cerebellar cortex

Spontaneous and evoked activities of nucleus interpositus neurons (IN) of the cerebellum were examined before and after cerebellar paravermal cortex lesions in cats anesthetized with alpha-chloralose. It was found that spontaneous activity increased dramatically following cortical ablation: before the lesion only 4% of cells encountered fired at a rate exceeding 80 impulses/sec., whereas up to 40% discharged at this rate postoperatively. Responses to paw stimulation were also altered: the initial excitation was lengthened from 8.5 to 15.8 msec; narrow; trough causing segmentation in this excitation, which seems to result from Purkinje cell inhibition, was absent; and the succeeding inhibitory period was reduced in duration by 50%. Also after the lesion there was a strong tendency for the neurons to discharge in bursts. It is suggested that changes in cell activity in the IN following cortical lesion unveil neural mechanisms of motor disturbances in lesioned cats.     

Walking in the American cockroach: the timing of motor activity in the legs during straight walking

The timing of bursts of motor activity in extensor muscles in the coxae of pairs of legs in intact freely walking American cockroaches was studied. The timing of bursts in adjacent and non-adjacent leg pairs generally reflected the common alternating tripod gait of these insects. Detailed study of the timing further revealed two previously unreported features. (1) The timing of extensor bursts in the middle legs relative to bursts in the rear legs was more variable than it was relative to those in the front legs. This difference in variability was statistically significant for the means of bursts when all insects were considered together as well as for bursts in individual insects. An apparent difference in variability of the timing of burst starts compared to burst ends for any one leg pair was not significant. (2) There was a shift in the timing of motor bursts relative to one another when an insect walked fast such that motor bursts in the middle legs tended to lag farther behind those in the front legs, and those in the rear legs tended to lag farther behind those in the middle legs compared to the timing during slow walking. This shift was apparent in both burst starts and burst ends, although more obvious in the former. It occurred in both ipsilateral and contralateral leg pairs, and in both the mean data and the data for individual insects. The implications of these characteristics of the timing data are discussed in terms of the neural organization of insect walking.     

Mu-delta opioid interactions. II: Beta-FNA inhibits DPDPE-induced increases in morphine EEG and EEG spectral power.

In the present study, the effects of beta-FNA on DPDPE-induced increases in morphine EEG and EEG power spectra were assessed. Adult female Sprague-Dawley rats were implanted with cortical EEG electrodes and permanent indwelling ICV and IV cannulae. Rats were administered ICV beta-FNA at 20 nmol or ICV sterile water. Then 18-24 h later, rats were administered ICV DPDPE at 2.5 nmol or ICV sterile water followed, 10 min later, by IV morphine at 3 mg/kg. Morphine-induced changes in EEG global (1-50 Hz) spectral parameters, the duration of morphine-induced high voltage EEG bursts, the period of EEG and behavioral excitation, and the latency to onset of slow-wave sleep were statistically analyzed using a one-way analysis of variance. beta-FNA pretreatment significantly decreased morphine-induced total spectral power seen in the DPDPE + morphine group. beta-FNA pretreatment also significantly decreased the duration of morphine-induced EEG bursts, the period of EEG and behavioral excitation, and the latency to onset of slow-wave sleep in the DPDPE + morphine group. These data, therefore, suggest that DPDPE may be increasing the effects of morphine on EEG through delta opioid receptors associated with the mu-delta opioid receptor complex.     

Development of patterns of activity in diaphragm of fetal lamb early in gestation

To examine the development of respiratory motor activity early in mammalian development and its relationship to nonrespiratory activity, we recorded spontaneous electromyogram activity from chronically instrumented fetal lambs over the period from 45 to 65 days' gestation (G45 to G65, term = G147). Two distinct forms of motor behavior were observed at G45 in recordings made from the costal diaphragm and longissimus dorsi muscles. The predominant behavior consisted of cycles of sustained, coincident activity in the two muscles alternating with periods of inactivity. The incidence of this type of activity declined between G45 and G65 and the cyclic nature of the discharges disappeared in most animals. The second form of motor behavior at G45 consisted of episodes of repetitive bursting activity lasting up to 20 min that were confined to the diaphragm. These bursts had a duration of 97.5 ± 8.3 ms (mean ± S.E.M.) and frequently occurred as doublets in which two bursts were separated by an intervening period of 100–200 ms. The mean duration of these bursts declined to 69.7 ± 7.7 ms at G65, doublets became rare, and bursts evolved a stereotyped form by G65 that was characterized by an abrupt onset and rapid decline in discharge intensity. Repetitive bursts of this form evolve into the mature respiratory motor pattern over the second half of gestation. At G45, episodes of repetitive bursting were almost always linked with episodes of sustained discharge, while at G65 these two forms of behavior were always segregated. We conclude that the neurons responsible for generating the respiratory rhythm in the lamb are assembled into a functional rhythm generator and make appropriate connections to motor output pathways as early as G45. The generation of the respiratory rhythm at G45 appears to be triggered by episodes of widespread motor activity that occur in both respiratory and nonrespiratory muscles. © 1996 John Wiley & Sons, Inc.     

Respiratory bursts at the midline of the rostral medulla of the lamprey

The contribution of a rostral crossed pathway to the coordination of fictive breathing was tested in isolated brains of adult lampreys, Ichthyomyzon unicuspis. Periodic bursts of small spikes were recorded at the midline at the rostral level of the V motor nuclei. These occurred prior to bursts by respiratory motoneurons in the IX-X cranial nerve roots. The bursts at the midline could be generated in the rostral half of the medulla, since they continued after isolation of the isthmic-trigeminal region by transections. Stimulation at the rostral midline excited respiratory motoneurons monosynaptically and could entrain or reset the respiratory rhythm. Sections of the midline sparing the rostral site still permitted bilateral synchronization of respiratory bursts. Alternatively, sections of the rostral midline still allowed coordination of respiratory bursts through crossed caudal pathways, although abnormal timing patterns were observed. It is concluded that the motor pattern for respiration is partly generated and coordinated in the rostral half of the medulla of the lamprey and is transmitted to respiratory motoneurons through descending pathways.     

Features of the spontaneous unit activity in the human thalamic parafascicular (CM-Pf) complex and its modification in functional cerebral changes

New data on neural organization of the human thalamic parafascicular (CM-Pf) complex were revealed with microelectrode technique during 11 stereotaxic operations in alert diskinetic patients suffering from the tonic forms of spasmodic torticollis. The data were obtained as follows: the functional heterogeneity in cellular organization of the human CM-Pf thalamic nuclei and the existence of three (A, B and C) different types of neurons in these thalamic nuclei: with the irregular discharges (A-type, 18%); with short (10-20 ms) bursts characterised by unstable rhythmic 2-5 Hz pattern and by the low threshold Ca2+ dependent K+ conductance (B-type, 77%); with long-lasting (0.1-2.0 s) bursts of high-frequency trains and constant interburst intervals (C-type, 5%). The functional cerebral changes after motor test performances were shown to be accompanied by appearance of transient modifications of the background unit activity pattern and by tendency towards an increase of neural activity local synchronisation with some stabilising of oscillatory rhythm of discharging B-type neurons. For the first time, a direct relationship between functional characteristics of the human thalamic CM-Pf units and the motor deviations was found in spasmodic torticollis patients.     

High pressure modifies respiratory activity in isolated rat brain stem-spinal cord

Exposure to hyperbaric pressure causes a constellation of motor disturbances and ventilatory difficulties in animals and humans. The present experiments were designed to examine the effects of hyperbaric pressure on the rhythmic activity of the respiratory center in the absence of peripheral sensory afferents by using the isolated brain stem-spinal cord preparation from newborn rats. In addition, we examined the effect of pressure on the response of the respiratory center to sensory input from the trigeminal and vagus cranial nerves. Hyperbaric pressure significantly depressed the mean inspiratory drive (frequency X time integral of single electrical bursts) in C5 but not in C1 ventral roots. Pressure also reduced the amount of inhibition on the respiratory activity normally exerted by trigeminal and vagal nerve stimulation and in some cases reversed it to excitation. It is concluded that in the absence of sensory input, exposure to hyperbaric pressure depresses central respiratory activity. However, in an intact system, it may alter the balance between excitation and inhibition and render the system hyperexcitable to the same sensory input.     

Cholinergic induction of seizures in the rat prefrontal cortex

Intracerebral microinjection of the cholinergic agonist, carbachol, into the medial prefrontal cortex of the rat, induced a profound behavioral syndrome consisting of repetitive, stereotyped forepaw treading in an upright posture. Electroencephalographic analysis revealed multiple bursts of sharp waves, 200-300 microV, accompanying the carbachol-elicited motor behavior. Pretreatment with intraperitoneal doses of three anticonvulsant drugs, clonazepam, diazepam, and pentobarbital, blocked the manifestation of the motor behavior. These observations suggest that activation of cholinergically innervated regions of the rat medial prefrontal cortex induces an atypical form of seizures.     

Abdominal ventilatory pattern in crickets depends on the stridulatory motor pattern

Abstract. Ventilatory motor patterns were recorded from abdominal muscles in crickets, Gryllus campestris L.and Teleogryllus commodus (Walker), at rest and during three types of stridulatory motor activity; calling, courtship and aggressive song.
Increases in ventilatory period were almost exclusively due to an increase of the pause between expiratory bursts, whereas abdominal ventilatory bursts remained constant at 200 ms.Ventilatory patterns depended on the stridulatory motor pattern and indicated that the same basic respiratory oscillator exists in both cricket species.
In G.campestris there was a strict 1:1 coupling between chirps and ventilatory bursts.In T.commodus such a relationship was also observed for the chirp part of the songs, but less strictly for the trill part of the calling song and not for the courtship song.In both species the onset of the ventilatory burst was within ± 100 ms of a stridulatory chirp.Ventilatory burst lasted longer the earlier they began before a stridulatory chirp.This suggests strongly that the stridulatory motor pattern terminates the expiratory burst, and thus influences the ventilatory motor pattern.