Ventrolateral lesions at the ponto-medullary junction and the effects of noradrenaline on respiratory rhythm in rat brainstem-spinal cord preparations.

Department of Physiology, Nippon Dental University, School of Life Dentistry at Tokyo, 1-9-20, Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan.
Life sciences (Impact Factor: 2.56). 07/2009; 85(7-8):322-6. DOI: 10.1016/j.lfs.2009.06.010
Source: PubMed

ABSTRACT We examined whether responses of respiratory frequency (fR) to noradrenaline (NA) were eliminated by mechanical lesions in the ventrolateral area at the ponto-medullary junction in preparations of newborn rat pons-medulla-spinal cord (PMS).
Preparations obtained from 2- to 4-day-old rats were superfused with artificial cerebrospinal fluid that was equilibrated with oxygenated (95% O2 plus 5% CO2 gas, and fR was monitored at the C4 ventral root at 24 degrees C. Bilateral lesions were made in the ventrolateral area between the VIth cranial nerve root and the anterior inferior cerebellar artery in PMS (n=11). The resting fR and response to exogenous NA (7 microM) were compared with those of medulla-spinal cord (MS) preparations (n=6). Immunohistochemistry of PMS preparations was performed to detect tyrosine hydroxylase (TH)-positive neurons at the ponto-medullary junction.
PMS preparations with the lesions had (1) a significantly higher resting fR but 2 significantly less fR facilitation after NA application than those of intact PMS preparations, and (3) significantly lower resting fR and (4) significantly less fR reduction after NA application than those of MS preparations. TH-positive neurons were detected in the region from the rostral dorsolateral to the caudal ventrolateral pons (the A5 area), as well as in the ventral area near the facial nucleus.
Results suggest that ventrolateral area at ponto-medullary junction plays a significant role in exogenous NA-induced fR changes under the influence of pons-induced tonic fR inhibition in newborn rat brainstem-spinal cord preparations.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Although the medulla oblongata contains the epicenter for respiratory rhythm generation, many other parts of the neuraxis play significant substratal roles in breathing. Accumulating evidence suggests that the pons contains several groups of neurons that may belong to the central respiratory system. This article will review data from microstimulation mapping and tract-tracing studies of the parabrachial complex (PB) and intertrigeminal region (ITR). Chemical activation of neurons in these areas has distinct effects on ventilatory and airway muscle activity. Tract-tracing experiments from functionally identified sites reveal specific respiratory-related sensory inputs and outputs that are likely anatomical substrates for these effects. The data suggest that an important physiological role for the rostral pons may be reflexive respiratory responses to airway stimuli.
    Respiratory Physiology & Neurobiology 12/2004; 143(2-3):115-25. · 2.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present review is to summarise available studies dealing with the respiratory control exerted by pontine noradrenergic neurones in neonatal and adult mammals. During the perinatal period, in vitro studies on neonatal rodents have shown that A5 and A6 neurones exert opposite modulations onto the respiratory rhythm generator, inhibitory and facilitatory respectively, that the anatomical support for these modulations already exists at birth, and that genetically induced alterations in the formation of A5 and A6 neurones affect the maturation of the respiratory rhythm generator, leading to lethal respiratory deficits at birth. The A5-A6 modulation of the respiratory rhythm generator is not transient, occurring solely during the perinatal period but it persists throughout life: A5 and A6 neurones display a respiratory-related activity, receive inputs from and send information to the medullary respiratory centres and contribute to the adaptation of adult breathing to physiological needs.
    Respiratory Physiology & Neurobiology 12/2004; 143(2-3):187-97. · 2.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The brainstem respiratory network can operate in multiple functional states engaging different state-dependent neural mechanisms. These mechanisms were studied in the in situ perfused rat brainstem-spinal cord preparation using sequential brainstem transections and administration of riluzole, a pharmacological blocker of persistent sodium current (INaP). Dramatic transformations in the rhythmogenic mechanisms and respiratory motor pattern were observed after removal of the pons and subsequent medullary transactions down to the rostral end of pre-Bötzinger complex (pre-BötC). A computational model of the brainstem respiratory network was developed to reproduce and explain these experimental findings. The model incorporates several interacting neuronal compartments, including the ventral respiratory group (VRG), pre-BötC, Bötzinger complex (BötC), and pons. Simulations mimicking the removal of circuit components following transections closely reproduce the respiratory motor output patterns recorded from the intact and sequentially reduced brainstem preparations. The model suggests that both the operating rhythmogenic mechanism (i.e., network-based or pacemaker-driven) and the respiratory pattern generated (e.g., three-phase, two-phase, or one-phase) depend on the state of the pre-BötC (expression of INaP-dependent intrinsic rhythmogenic mechanisms) and the BötC (providing expiratory inhibition in the network). At the same time, tonic drives from pons and multiple medullary chemoreceptive sites appear to control the state of these compartments and hence the operating rhythmogenic mechanism and motor pattern. Our results suggest that the brainstem respiratory network has a spatial (rostral-to-caudal) organization extending from the rostral pons to the VRG, in which each functional compartment is controlled by more rostral compartments. The model predicts a continuum of respiratory network states relying on different contributions of intrinsic cellular properties versus synaptic interactions for the generation and control of the respiratory rhythm and pattern.
    Progress in brain research 02/2007; 165:201-20. · 4.19 Impact Factor