1,721,033 research outputs found

    Pontine respiratory activity involved in inspiratory/expiratory phase transition

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    Control of the timing of the inspiratory/expiratory (IE) phase transition is a hallmark of respiratory pattern formation. In principle, sensory feedback from pulmonary stretch receptors (Breuer-Hering reflex, BHR) is seen as the major controller for the IE phase transition, while pontine-based control of IE phase transition by both the pontine Kolliker-Fuse nucleus (KF) and parabrachial complex is seen as a secondary or backup mechanism. However, previous studies have shown that the BHR can habituate in vivo. Thus, habituation reduces sensory feedback, so the role of the pons, and specifically the KF, for IE phase transition may increase dramatically. Pontine-mediated control of the IE phase transition is not completely understood. In the present review, we discuss existing models for ponto-medullary interaction that may be involved in the control of inspiratory duration and IE transition. We also present intracellular recordings of pontine respiratory units derived from an in situ intra-arterially perfused brainstem preparation of rats. With the absence of lung inflation, this preparation generates a normal respiratory pattern and many of the recorded pontine units demonstrated phasic respiratory-related activity. The analysis of changes in membrane potentials of pontine respiratory neurons has allowed us to propose a number of pontine-medullary interactions not considered before. The involvement of these putative interactions in pontine-mediated control of IE phase transitions is discussed

    The Kolliker-Fuse nucleus gates the postinspiratory phase of the respiratory cycle to control inspiratory off-switch and upper airway resistance in rat

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    Lesion or pharmacological manipulation of the dorsolateral pons can transform the breathing pattern to apneusis (pathological prolonged inspiration). Apneusis reflects a disturbed inspiratory off-switch mechanism (IOS) leading to a delayed phase transition from inspiration to expiration. Under intact conditions the IOS is irreversibly mediated via activation of postinspiratory (PI) neurons within the respiratory network. In parallel, populations of laryngeal premotoneurons manifest the IOS by a brief glottal constriction during the PI phase. We investigated effects of pontine excitation (glutamate injection) or temporary lesion after injection of a GABA-receptor agonist (isoguvacine) on the strength of PI-pool activity determined from respiratory motor outputs or kinesiological measurements of laryngeal resistance in a perfused brainstem preparation. Glutamate microinjections into distinct parts of the pontine Kolliker-Fuse nucleus (KF) evoked a tonic excitation of PI-motor activity or sustained laryngeal constriction accompanied by prolongation of the expiratory phase. Subsequent isoguvacine microinjections at the same loci abolished PI-motor or laryngeal constrictor activity, triggered apneusis and established a variable and decreased breathing frequency. In summary, we revealed that excitation or inhibition of defined areas within the KF activated and blocked PI activity and, consequently, IOS. Therefore, we conclude, first, that descending KF inputs are essential to gate PI activity required for a proper pattern formation and phase control within the respiratory network, at least during absence of pulmonary stretch receptor activity and, secondly, that the KF contains large numbers of laryngeal PI premotor neurons that might have a key role in the regulation of upper airway resistance during reflex control and vocalization

    Imaging of respiratory-related population activity with single-cell resolution

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    The pre-Botzinger complex (PBC) in the rostral ventrolateral medulla contains a kernel involved in respiratory rhythm generation. So far, its respiratory activity has been analyzed predominantly by electrophysiological approaches. Recent advances in fluorescence imaging now allow for the visualization of neuronal population activity in rhythmogenic networks. In the respiratory network, voltage-sensitive dyes have been used mainly, so far, but their low sensitivity prevents an analysis of activity patterns of single neurons during rhythmogenesis. We now have succeeded in using more sensitive Ca2+ imaging to study respiratory neurons in rhythmically active brain stem slices of neonatal rats. For the visualization of neuronal activity, fluo-3 was suited best in terms of neuronal specificity, minimized background fluorescence, and response magnitude. The tissue penetration of fluo-3 was improved by hyperosmolar treatment (100 mM mannitol) during dye loading. Rhythmic population activity was imaged with single-cell resolution using a sensitive charge-coupled device camera and a x20 objective, and it was correlated with extracellularly recorded mass activity of the contralateral PBC. Correlated optical neuronal activity was obvious online in 29% of slices. Rhythmic neurons located deeper became detectable during offline image processing. Based on their activity patterns, 74% of rhythmic neurons were classified as inspiratory and 26% as expiratory neurons. Our approach is well suited to visualize and correlate the activity of several single cells with respiratory network activity. We demonstrate that neuronal synchronization and possibly even network configurations can be analyzed in a noninvasive approach with single-cell resolution and at frame rates currently not reached by most scanning-based imaging techniques

    The emerging role of the parabrachial complex in the generation of wakefulness drive and its implication for respiratory control

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    The parabrachial complex is classically seen as a major neural knot that transmits viscero- and somatosensory information toward the limbic and thalamic forebrain. In the present review we summarize recent findings that imply an emerging role of the parabrachial complex as an integral part of the ascending reticular arousal system, which promotes wakefulness and cortical activation. The ascending parabrachial projections that target wake-promoting hypothalamic areas and the basal forebrain are largely glutamatergic. Such fast synaptic transmission could be even more significant in promoting wakefulness and its characteristic pattern of cortical activation than the cholinergic or mono-aminergic ascending pathways that have been emphasized extensively in the past. A similar role of the parabrachial complex could also apply for its more established function in control of breathing. Here the parabrachial respiratory neurons may modulate and adapt breathing via the control of respiratory phase transition and upper airway patency, particularly during respiratory and non-respiratory behavior associated with wakefulness
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