Thoracic Motoneurons Research Articles

Re-evaluation of the symptoms of Hirayama disease through anatomical perspective.

Hirayama disease is a rare disease of the anterior horn motor neuron caused by compression of the cervical spinal cord when the neck is flexed. Cervical myelopathy may accompany the disease. It is characterized by symmetrical or asymmetrical muscle weakness and atrophy of muscles innervated by lower cervical and upper thoracic motor neurons. We recorded two male cases of Hirayama disease between the ages of 15 and 21 based on magnetic resonance imaging (MRI) features obtained from the cervical neutral state and from the flexion position which appeared in the right upper extremity. Loss of strength and atrophy in the right upper extremities was existent in clinical findings of these patients. When MRI was taken in the flexion position, there were dilated veins as hypointense signal void on T2 weighted series in posterior epidural area. The contrast enhancement was seen on these veins. It was observed that the posterior dura was displaced anteriorly and the anterior subarachnoid space was narrow. In cases which show clinical findings such as atrophy and loss of strength, having normal MRI results obtained in the neutral position makes it difficult to diagnose Hirayama Disease. In case of a suspicion of Hirayama disease the diagnosis can be made more easily by MRI taken in the flexion position. These case reports aim to bring Hirayama disease to mind and optimize the management of affected individuals.

Delayed viral vector mediated delivery of neurotrophin-3 improves skilled hindlimb function and stability after thoracic contusion

Intramuscular injection of an Adeno-associated viral vector serotype 1 (AAV1) encoding Neurotrophin-3 (NT3) into hindlimb muscles 24 h after a severe T9 spinal level contusion in rats has been shown to induce lumbar spinal neuroplasticity, partially restore locomotive function and reduce spasms during swimming. Here we investigate whether a targeted delivery of NT3 to lumbar and thoracic motor neurons 48 h following a severe contusive injury aids locomotive recovery in rats. AAV1-NT3 was injected bilaterally into the tibialis anterior, gastrocnemius and rectus abdominus muscles 48-h following trauma, persistently elevating serum levels of the neurotrophin. NT3 modestly improved trunk stability, accuracy of stepping during skilled locomotion, and alternation of the hindlimbs during swimming, but it had no effect on gross locomotor function in the open field. The number of vGlut1+ boutons, likely arising from proprioceptive afferents, on gastrocnemius α-motor neurons was increased after injury but normalised following NT3 treatment, suggestive of a mechanism in which functional benefits may be mediated through proprioceptive feedback. Ex vivo MRI revealed substantial loss of grey and white matter at the lesion epicentre but no effect of delayed NT3 treatment to induce neuroprotection. Lower body spasms and hyperreflexia of an intrinsic paw muscle were not reliably induced in this severe injury model suggesting a more complex anatomical or physiological cause to their induction. We have shown that delayed intramuscular AAV-NT3 treatment can promote recovery in skilled stepping and coordinated swimming, supporting a role for NT3 as a therapeutic strategy for spinal injuries potentially through modulation of somatosensory feedback.

Functional organization of vestibulospinal inputs on thoracic motoneurons responsible for trunk postural control in Xenopus.

Vestibulospinal reflexes participate in postural control. How this is achieved has not been investigated fully. We combined electrophysiological, neuroanatomical and imaging techniques to decipher the vestibulospinal network controlling the activation of back and limb muscles responsible for postural adjustments. We describe two distinct pathways activating either thoracic postural motoneurons alone or thoracic and lumbar motoneurons together, with the latter co-ordinating specifically hindlimb extensors and postural back muscles. In vertebrates, trunk postural stabilization is known to rely mainly on direct vestibulospinal inputs on spinal axial motoneurons. However, a substantial role of central spinal commands ascending from lumbar segments is not excluded during active locomotion. In the adult Xenopus, a lumbar drive dramatically overwhelms the descending inputs onto thoracic postural motoneurons during swimming. Given that vestibulospinal fibres also project onto the lumbar segments that shelter the locomotor generators, we investigated whether such a lumbo-thoracic pathway may relay vestibular information and consequently, also be involved in the control of posture at rest. We show that thoracic postural motoneurons exhibit particular dendritic spatial organization allowing them to gather information from both sides of the cord. In response to passive head motion, these motoneurons display both early and delayed discharges, with the latter occurring in phase with ipsilateral hindlimb extensor bursts. We demonstrate that both vestibulospinal and lumbar ascending fibres converge onto postural motoneurons, and that thoracic motoneurons monosynaptically respond to the electrical stimulation of either pathway. Finally, we show that vestibulospinal fibres project to and activate lumbar interneurons with thoracic projections. Taken together, our results complete the scheme of the vestibulospinal control of posture by illustrating the existence of a novel, indirect pathway, which implicates lumbar interneurons relaying vestibular inputs to thoracic motoneurons, and participating in global body postural stabilization in the absence of active locomotion.

Descending octopaminergic neurons modulate sensory-evoked activity of thoracic motor neurons in stick insects.

Neuromodulatory neurons located in the brain can influence activity in locomotor networks residing in the spinal cord or ventral nerve cords of invertebrates. How inputs to and outputs of neuromodulatory descending neurons affect walking activity is largely unknown. With the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and immunohistochemistry, we show that a population of dorsal unpaired median (DUM) neurons descending from the gnathal ganglion to thoracic ganglia of the stick insect Carausius morosus contains the neuromodulatory amine octopamine. These neurons receive excitatory input coupled to the legs' stance phases during treadmill walking. Inputs did not result from connections with thoracic central pattern-generating networks, but, instead, most are derived from leg load sensors. In excitatory and inhibitory retractor coxae motor neurons, spike activity in the descending DUM (desDUM) neurons increased depolarizing reflexlike responses to stimulation of leg load sensors. In these motor neurons, descending octopaminergic neurons apparently functioned as components of a positive feedback network mainly driven by load-detecting sense organs. Reflexlike responses in excitatory extensor tibiae motor neurons evoked by stimulations of a femur-tibia movement sensor either are increased or decreased or were not affected by the activity of the descending neurons, indicating different functions of desDUM neurons. The increase in motor neuron activity is often accompanied by a reflex reversal, which is characteristic for actively moving animals. Our findings indicate that some descending octopaminergic neurons can facilitate motor activity during walking and support a sensory-motor state necessary for active leg movements.NEW & NOTEWORTHY We investigated the role of descending octopaminergic neurons in the gnathal ganglion of stick insects. The neurons become active during walking, mainly triggered by input from load sensors in the legs rather than pattern-generating networks. This report provides novel evidence that octopamine released by descending neurons on stimulation of leg sense organs contributes to the modulation of leg sensory-evoked activity in a leg motor control system.

Further observations on cardiac modulation of thoracic motoneuron discharges

Previous analyses of recordings of alpha motoneuron discharges from branches of the intercostal and abdominal nerves in anesthetized cats under neuromuscular blockade demonstrated modulation with the cardiac cycle. This modulation was interpreted as evidence that thoracic somatosensory afferents, most likely muscle spindles, provide a signal to the CNS that could contribute to cardiac interoception. Here, two aspects of these observations have been extended. First, new measurements of thoracic and abdominal EMG activity in spontaneously breathing dogs show that a very similar modulation exists in these rather different circumstances. Second, further analysis of the cat recordings shows that cardiac modulation of the discharges of bulbospinal neurons that transmit the expiratory drive to thoracic motoneurons is weak and of an inappropriate time-course to be a contributor to the effect seen in the motoneurons.

Intravenous hydrogen sulfide does not induce neuroprotection after aortic balloon occlusion-induced spinal cord ischemia/reperfusion injury in a human-like porcine model of ubiquitous arteriosclerosis

ObjectiveIn rodents, intravenous sulfide protected against spinal cord ischemia/reperfusion (I/R) injury during aortic balloon occlusion. We investigated the effect of intravenous sulfide on aortic occlusion-induced porcine spinal cord I/R injury.MethodsAnesthetized and mechanically ventilated “familial hypercholesterolemia Bretoncelles Meishan” (FBM) pigs with high-fat-diet-induced hypercholesterolemia and atherosclerosis were randomized to receive either intravenous sodium sulfide 2 h (initial bolus, 0.2 mg kg body weight (bw)−1; infusion, 2 mg kg bw−1 h−1; n = 4) or vehicle (sodium chloride, n = 4) prior to 45 min of thoracic aortic balloon occlusion and for 8 h during reperfusion (infusion, 1 mg kg bw−1 h−1). During reperfusion, noradrenaline was titrated to maintain blood pressure at above 80% of the baseline level. Spinal cord function was assessed by motor evoked potentials (MEPs) and lower limb reflexes using a modified Tarlov score. Spinal cord tissue damage was evaluated in tissue collected at the end of experiment using hematoxylin and eosin and Nissl staining.ResultsA balloon occlusion time of 45 min resulted in marked ischemic neuron damage (mean of 16% damaged motoneurons in the anterior horn of all thoracic motor neurons) in the spinal cord. In the vehicle group, only one animal recovered partial neuronal function with regain of MEPs and link motions at each time point after deflating. All other animals completely lost neuronal functions. The intravenous application of sodium sulfide did not prevent neuronal cell injury and did not confer to functional recovery.ConclusionIn a porcine model of I/R injury of the spinal cord, treatment with intravenous sodium sulfide had no protective effect in animals with a pre-existing arteriosclerosis.

C4BP-mediated complement evasion in streptococcal infections: How the good guys turn bad

Previous analyses of recordings of alpha motoneuron discharges from branches of the intercostal and abdominal nerves in anesthetized cats under neuromuscular blockade demonstrated modulation with the cardiac cycle. This modulation was interpreted as evidence that thoracic somatosensory afferents, most likely muscle spindles, provide a signal to the CNS that could contribute to cardiac interoception. Here, two aspects of these observations have been extended. First, new measurements of thoracic and abdominal EMG activity in spontaneously breathing dogs show that a very similar modulation exists in these rather different circumstances. Second, further analysis of the cat recordings shows that cardiac modulation of the discharges of bulbospinal neurons that transmit the expiratory drive to thoracic motoneurons is weak and of an inappropriate time-course to be a contributor to the effect seen in the motoneurons.

Ontogeny and development of the tritocerebral commissure giant (TCG): an identified neuron in the brain of the grasshopper Schistocerca gregaria.

The tritocerebral commissure giant (TCG) of the grasshopper Schistocerca gregaria is one of the best anatomically and physiologically described arthropod brain neurons. A member of the so-called Ventral Giant cluster of cells, it integrates sensory information from visual, antennal and hair receptors, and synapses with thoracic motor neurons in order to initiate and regulate flight behavior. Its ontogeny, however, remains unclear. In this study, we use bromodeoxyuridine incorporation and cyclin labeling to reveal proliferative neuroblasts in the region of the embryonic brain where the ventral giant cluster is located. Engrailed labeling confirms the deutocerebral identity of this cluster. Comparison of soma locations and initial neurite projections into tracts of the striate deutocerebrum help identify the cells of the ventral cluster in both the embryonic and adult brain. Reconstructions of embryonic cell lineages suggest deutocerebral NB1 as being the putative neuroblast of origin. Intracellular dye injection coupled with immunolabeling against neuron-specific horseradish peroxidase is used to identify the VG1 (TCG) and VG3 neurons from the ventral cluster in embryonic brain slices. Dye injection and backfilling are used to document axogenesis and the progressive expansion of the dendritic arbor of the TCG from mid-embryogenesis up to hatching. Comparative maps of embryonic neuroblasts from several orthopteroid insects suggest equivalent deutocerebral neuroblasts from which the homologous TCG neurons already identified in the adult brain could originate. Our data offer the prospect of identifying further lineage-related neurons from the cluster and so understand a brain connectome from both a developmental and evolutionary perspective.

Neuropathology in respiratory-related motoneurons in young Pompe (Gaa−/−) mice

Respiratory and/or lingual dysfunction are among the first motor symptoms in Pompe disease, a disorder resulting from absence or dysfunction of the lysosomal enzyme acid α-glucosidase (GAA). Here, we histologically evaluated the medulla, cervical and thoracic spinal cords in 6 weeks old asymptomatic Pompe (Gaa−/−) mice to determine if neuropathology in respiratory motor regions has an early onset. Periodic acid-Schiff (PAS) staining indicated glycogen accumulation was exclusively occurring in Gaa−/− hypoglossal, mid-cervical and upper thoracic motoneurons. Markers of DNA damage (Tunel) and ongoing apoptosis (Cleaved Caspase 3) did not co-localize with PAS staining, but were prominent in a medullary region which included the nucleus tractus solitarius, and also in the thoracic spinal dorsal horn. We conclude that respiratory-related motoneurons are particularly susceptible to GAA deficiency and that neuronal glycogen accumulation and neurodegeneration may occur independently in early stage disease. The data support early therapeutic intervention in Pompe disease.

Commentary: Burst Firing in a Motion-Sensitive Neural Pathway Correlates with Expansion Properties of Looming Objects That Evoke Avoidance Behaviors.

Commentary: Burst Firing in a Motion-Sensitive Neural Pathway Correlates with Expansion Properties of Looming Objects That Evoke Avoidance Behaviors.

Functional plasticity in the respiratory drive to thoracic motoneurons in the segment above a chronic lateral spinal cord lesion.

A previous neurophysiological investigation demonstrated an increase in functional projections of expiratory bulbospinal neurons (EBSNs) in the segment above a chronic lateral thoracic spinal cord lesion that severed their axons. We have now investigated how this plasticity might be manifested in thoracic motoneurons by measuring their respiratory drive and the connections to them from individual EBSNs. In anesthetized cats, simultaneous recordings were made intracellularly from motoneurons in the segment above a left-side chronic (16 wk) lesion of the spinal cord in the rostral part of T8, T9, or T10 and extracellularly from EBSNs in the right caudal medulla, antidromically excited from just above the lesion but not from below. Spike-triggered averaging was used to measure the connections between pairs of EBSNs and motoneurons. Connections were found to have a very similar distribution to normal and were, if anything (nonsignificantly), weaker than normal, being present for 42/158 pairs, vs. 55/154 pairs in controls. The expiratory drive in expiratory motoneurons appeared stronger than in controls but again not significantly so. Thus we conclude that new connections made by the EBSNs following these lesions were made to neurons other than α-motoneurons. However, a previously unidentified form of functional plasticity was seen in that there was a significant increase in the excitation of motoneurons during postinspiration, being manifest either in increased incidence of expiratory decrementing respiratory drive potentials or in an increased amplitude of the postinspiratory depolarizing phase in inspiratory motoneurons. We suggest that this component arose from spinal cord interneurons.

Origin of thoracic spinal network activity during locomotor-like activity in the neonatal rat.

Effective quadrupedal locomotor behaviors require the coordination of many muscles in the limbs, back, neck, and tail. Because of the spinal motoneuronal somatotopic organization, motor coordination implies interactions among distant spinal networks. Here, we investigated some of the interactions between the lumbar locomotor networks that control limb movements and the thoracic networks that control the axial muscles involved in trunk movement. For this purpose, we used an in vitro isolated newborn rat spinal cord (from T2 to sacrococcygeal) preparation. Using extracellular ventral root recordings, we showed that, while the thoracic cord possesses an intrinsic rhythmogenic capacity, the lumbar circuits, if they are rhythmically active, will entrain the rhythmicity of the thoracic circuitry. However, if the lumbar circuits are rhythmically active, these latter circuits will entrain the rhythmicity of the thoracic circuitry. Blocking the synaptic transmission in some thoracic areas revealed that the lumbar locomotor network could trigger locomotor bursting in distant thoracic segments through short and long propriospinal pathways. Patch-clamp recordings revealed that 72% of the thoracic motoneurons (locomotor-driven motoneurons) expressed membrane potential oscillations and spiking activity coordinated with the locomotor activity expressed by the lumbar cord. A biphasic excitatory (glutamatergic)/inhibitory (glycinergic) synaptic drive was recorded in thoracic locomotor-driven motoneurons. Finally, we found evidence that part of this locomotor drive involved a monosynaptic component coming directly from the lumbar locomotor network. We conclude that the lumbar locomotor network plays a central role in the generation of locomotor outputs in the thoracic cord by acting at both the premotoneuronal and motoneuronal levels.

Specificity in monosynaptic and disynaptic bulbospinal connections to thoracic motoneurones in the rat

The respiratory activity in the intercostal nerves of the rat is unusual, in that motoneurones of both branches of the intercostal nerves, internal and external, are activated during expiration. Here, the pathways involved in that activation were investigated in anaesthetised and in decerebrate rats by cross-correlation and by intracellular spike-triggered averaging from expiratory bulbospinal neurones (EBSNs), with a view to revealing specific connections that could be used in studies of experimental spinal cord injury. Decerebrate preparations, which showed the strongest expiratory activity, were found to be the most suitable for these measurements. Cross-correlations in these preparations showed monosynaptic connections from 16/19 (84%) of EBSNs, but only to internal intercostal nerve motoneurones (24/37, 65% of EBSN/nerve pairs), whereas disynaptic connections were seen for external intercostal nerve motoneurones (4/19, 21% of EBSNs or 7/25, 28% of EBSN/nerve pairs). There was evidence for additional disynaptic connections to internal intercostal nerve motoneurones. Intracellular spike-triggered averaging revealed excitatory postsynaptic potentials, which confirmed these connections. This is believed to be the first report of single descending fibres that participate in two different pathways to two different groups of motoneurones. It is of interest compared with the cat, where only one group of motoneurones is activated during expiration and only one of the pathways has been detected. The specificity of the connections could be valuable in studies of plasticity in pathological situations, but care will be needed in studying connections in such situations, because their strength was found here to be relatively weak.

Selective activation of respiratory thoracic efferents in the spinal cord of the in situ rat preparation

Previous studies of respiratory plasticity have focused primarily on phrenic motoneurons (PM) in the cervical spinal cord, while little is known about the intercostal (IC) motor system. Recent reports suggest that IC muscle activity is only modestly impaired after unilateral cervical spinal cord injury (SCI), therefore, we hypothesized that respiratory thoracic motoneurons are capable of greater plasticity than PMs. To test this hypothesis, we simultaneously recorded activity from the left phrenic nerve (PNA) and thoracic ventral roots in the perfused in situ rat. Preparations were exposed to repeated bouts of hypercapnia (9% CO2/91% O2) alternated with baseline recovery periods (5%CO2/95%O2); and/or to periods of relative hypoxia (40% O2/5% CO2/55% N2) and recovery (95%O2/5%CO2). During both exposures, the relative increase in inspiratory‐related activity was significantly greater in the thoracic efferents compared to the phrenic nerve. Further, thoracic activity showed enhanced progressive augmentation compared to the phrenic nerve during each successive perturbation. We conclude that respiratory thoracic efferents have a greater capacity for dynamic plasticity in response to both hypercapnia and hypoxia. We suggest that compensation by the IC motor system may be a significant spontaneous mechanism for respiratory recovery after SCI and could be a key target for therapeutic interventions.

Genetic and Functional Modularity of Hox Activities in the Specification of Limb-Innervating Motor Neurons

A critical step in the assembly of the neural circuits that control tetrapod locomotion is the specification of the lateral motor column (LMC), a diverse motor neuron population targeting limb musculature. Hox6 paralog group genes have been implicated as key determinants of LMC fate at forelimb levels of the spinal cord, through their ability to promote expression of the LMC-restricted genes Foxp1 and Raldh2 and to suppress thoracic fates through exclusion of Hoxc9. The specific roles and mechanisms of Hox6 gene function in LMC neurons, however, are not known. We show that Hox6 genes are critical for diverse facets of LMC identity and define motifs required for their in vivo specificities. Although Hox6 genes are necessary for generating the appropriate number of LMC neurons, they are not absolutely required for the induction of forelimb LMC molecular determinants. In the absence of Hox6 activity, LMC identity appears to be preserved through a diverse array of Hox5–Hox8 paralogs, which are sufficient to reprogram thoracic motor neurons to an LMC fate. In contrast to the apparently permissive Hox inputs to early LMC gene programs, individual Hox genes, such as Hoxc6, have specific roles in promoting motor neuron pool diversity within the LMC. Dissection of motifs required for Hox in vivo specificities reveals that either cross-repressive interactions or cooperativity with Pbx cofactors are sufficient to induce LMC identity, with the N-terminus capable of promoting columnar, but not pool, identity when transferred to a heterologous homeodomain. These results indicate that Hox proteins orchestrate diverse aspects of cell fate specification through both the convergent regulation of gene programs regulated by many paralogs and also more restricted actions encoded through specificity determinants in the N-terminus.

Muscarinic control of AMPA receptor responsiveness in mouse spinal cord motoneurons

A cholinergic synaptic input has been highlighted in recent years as an important modulator of motoneuron excitability. In the present study, it was examined whether, as in other regions, the cholinergic inputs on spinal motoneurons modulate the glutamatergic synaptic activity, evoked by electrical stimulation at the dorsolateral funiculus. The present results show that the pharmacological stimulation of muscarinic receptors produces a selective depression of AMPA-mediated glutamatergic activity in thoracic and lumbar spinal motoneurons. This effect does not involve a change in transmitter release and occurs both on synaptic currents and on AMPA responses evoked by photolysis of MNI-glutamate. Thus, it is concluded that muscarinic modulation occurs at the postsynaptic level. The results suggest that cholinergic inputs contacting motoneurons, which are known to increase motoneuron excitability, also directly interfere within coming synaptic inputs by changing their amplitudes.

Constitutive Activation of Ca2+/Calmodulin-Dependent Protein Kinase II during Development Impairs Central Cholinergic Transmission in a Circuit Underlying Escape Behavior inDrosophila

Development of neural circuitry relies on precise matching between correct synaptic partners and appropriate synaptic strength tuning. Adaptive developmental adjustments may emerge from activity and calcium-dependent mechanisms. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been associated with developmental synaptic plasticity, but its varied roles in different synapses and developmental stages make mechanistic generalizations difficult. In contrast, we focused on synaptic development roles of CaMKII in a defined sensory-motor circuit. Thus, different forms of CaMKII were expressed with UAS-Gal4 in distinct components of the giant fiber system, the escape circuit of Drosophila, consisting of photoreceptors, interneurons, motoneurons, and muscles. The results demonstrate that the constitutively active CaMKII-T287D impairs development of cholinergic synapses in giant fiber dendrites and thoracic motoneurons, preventing light-induced escape behavior. The locus of the defects is postsynaptic as demonstrated by selective expression of transgenes in distinct components of the circuit. Furthermore, defects among these cholinergic synapses varied in severity, while the glutamatergic neuromuscular junctions appeared unaffected, demonstrating differential effects of CaMKII misregulation on distinct synapses of the same circuit. Limiting transgene expression to adult circuits had no effects, supporting the role of misregulated kinase activity in the development of the system rather than in acutely mediating escape responses. Overexpression of wild-type transgenes did not affect circuit development and function, suggesting but not proving that the CaMKII-T287D effects are not due to ectopic expression. Therefore, regulated CaMKII autophosphorylation appears essential in central synapse development, and particular cholinergic synapses are affected differentially, although they operate via the same nicotinic receptor.

Segmental differences in firing properties and potassium currents inDrosophilalarval motoneurons

Potassium currents play key roles in regulating motoneuron activity, including functional specializations that are important for locomotion. The thoracic and abdominal segments in the Drosophila larval ganglion have repeated arrays of motoneurons that innervate body-wall muscles used for peristaltic movements during crawling. Although abdominal motoneurons and their muscle targets have been studied in detail, owing, in part, to their involvement in locomotion, little is known about the cellular properties of motoneurons in thoracic segments. The goal of this study was to compare firing properties among thoracic motoneurons and the potassium currents that influence them. Whole-cell, patch-clamp recordings performed from motoneurons in two thoracic and one abdominal segment revealed both transient and sustained voltage-activated K(+) currents, each with Ca(++)-sensitive and Ca(++)-insensitive [A-type, voltage-dependent transient K(+) current (I(Av))] components. Segmental differences in the expression of voltage-activated K(+) currents were observed. In addition, we demonstrate that Shal contributes to I(Av) currents in the motoneurons of the first thoracic segment.

Patterns of expiratory and inspiratory activation for thoracic motoneurones in the anaesthetized and the decerebrate rat

The nervous control of expiratory muscles is less well understood than that of the inspiratory muscles, particularly in the rat. The patterns of respiratory discharges in adult rats were therefore investigated for the muscles of the caudal intercostal spaces, with hypercapnia and under either anaesthesia or decerebration. With neuromuscular blockade and artificial ventilation, efferent discharges were present for both inspiration and expiration in both external and internal intercostal nerves. This was also the case for proximal internal intercostal nerve branches that innervate only internal intercostal and subcostalis muscles. If active, this region of muscle in other species is always expiratory. Here, inspiratory bursts were almost always present. The expiratory activity appeared only gradually and intermittently, when the anaesthesia was allowed to lighten or as the pre-decerebration anaesthesia wore off. The intermittent appearance is interpreted as the coupling of a slow medullary expiratory oscillator with a faster inspiratory one. The patterns of nerve discharges, in particular the inspiratory or biphasic activation of the internal and subcostalis layers, were confirmed by observations of equivalent patterns of EMG discharges in spontaneously breathing preparations, using denervation procedures to identify which muscles generated the signals. Some motor units were recruited in both inspiratory and expiratory bursts. These patterns of activity have not previously been described and have implications both for the functional role of multiple respiratory oscillators in the adult and for the mechanical actions of the muscles of the caudal intercostal spaces, including subcostalis, which is a partly bisegmental muscle.

Multiple phases of excitation and inhibition in central respiratory drive potentials of thoracic motoneurones in the rat

Intracellular recordings were made from motoneurones with axons in the intercostal nerves of T9 or T10 in adult rats, with neuromuscular blockade and artificial ventilation, under hypercapnia and under either anaesthesia or decerebration. In nearly all motoneurones, central respiratory drive potentials (CRDPs) were seen, which included an excitatory wave in inspiration, in expiration, or in both of these. This was the case both for motoneurones with axons in the internal intercostal nerve (n = 81) and for those with axons in the external intercostal nerve (n = 5). In the decerebrates, motoneurones with purely inspiratory CRDPs were rare (1/44), but those excited in both phases (showing biphasic CRDPs) were common (22/44). For about one-third of biphasic CRDPs (11/30), the inspiratory depolarization was seen to reverse to a hyperpolarization when the motoneurone was depolarized, which was interpreted as indicating concurrent inhibition and excitation during this phase. A few motoneurones were seen where depolarization revealed signs of inhibition in both phases. The results confirm the novel observations of biphasic excitation in individual intercostal nerve branches, EMG sites and motor units reported in a companion paper. They also provide new insights into the functional roles of inhibition in motoneurones physiologically activated in natural rhythmic behaviours.