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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The pre-Bötzinger complex is a small region in the mammalian brainstem involved in generation of the respiratory rhythm. As shown in vitro, this region, under certain conditions, can generate endogenous rhythmic bursting activity. Our investigation focused on the conditions that may induce this bursting behaviour. A computational model of a population of pacemaker neurons in the pre-Bötzinger complex was developed and analysed. Each neuron was modelled in the Hodgkin–Huxley style and included persistent sodium and delayed-rectifier potassium currents. We found that the firing behaviour of the model strongly depended on the expression of these currents. Specifically, bursting in the model could be induced by a suppression of delayed-rectifier potassium current (either directly or via an increase in extracellular potassium concentration, [K+]o) or by an augmentation of persistent sodium current. To test our modelling predictions, we recorded endogenous population activity of the pre-Bötzinger complex and activity of the hypoglossal (XII) nerve from in vitro transverse brainstem slices (700 µm) of neonatal rats (P0–P4). Rhythmic activity was absent at 3 mm[K+]o but could be triggered by either the elevation of [K+]o to 5–7 mm or application of potassium current blockers (4-AP, 50–200 µm, or TEA, 2 or 4 mm), or by blocking aerobic metabolism with NaCN (2 mm). This rhythmic activity could be abolished by the persistent sodium current blocker riluzole (25 or 50 µm). These findings are discussed in the context of the role of endogenous bursting activity in the respiratory rhythm generation in vivo vs. in vitro and during normal breathing in vivo vs. gasping.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 16 (2002), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: There is limited information regarding the integration of visceral and somatic afferents within the nucleus of the solitary tract (NTS). We studied the interaction of nociceptive and baroreceptive inputs in this nucleus in an in situ arterially perfused, un-anaesthetized decerebrate preparation of rat. At the systemic level, the gain of the cardiac component of the baroreceptor reflex was attenuated significantly by noxious mechanical stimulation of a forepaw. This baroreceptor reflex depression was mimicked by NTS microinjection of substance P and antagonized by microinjection of either bicuculline (a GABAA receptor antagonist) or a neurokinin type 1 (NK1) receptor antagonist (CP-99,994). The substance P effect was also blocked by a bilateral microinjection of bicuculline, at a dose that was without effect on basal baroreceptor reflex gain. Baroreceptive NTS neurons were defined by their excitatory response following increases in pressure within the ipsilateral carotid sinus. In 27 of 34 neurons the number of evoked spikes from baroreceptor stimulation was reduced significantly by concomitant electrical stimulation of the brachial nerve (P 〈 0.01). Furthermore, the attenuation of baroreceptor inputs to NTS neurons by brachial nerve stimulation was prevented by pressure-ejection of bicuculline from a multi-barrelled microelectrode (n = 8). In a separate population of 17 of 45 cells tested, brachial nerve stimulation evoked an excitatory response that was antagonized by blockade of NK1 receptors. We conclude that nociceptive afferents activate NK1 receptors, which in turn excite GABAergic interneurons impinging on cells mediating the cardiac component of the baroreceptor reflex.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 10 (1998), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Unmyelinated vagal afferents from the heart terminate within the nucleus tractus solitarii (NTS) located in the dorsomedial medulla. The neurotransmitter and postsynaptic receptors mediating information from cardiac vagal receptors to the NTS are unknown. This study determined the effects of neurokinin-1 (NK1) receptor blockade on: (i) the reflex response evoked following aortic root injection of either veratridine (1–3 μg/kg) or bradykinin (80–300 ng/kg) to stimulate cardiac receptors in in vivo anaesthetized mice; and (ii) the evoked synaptic response of cardioreceptive NTS neurons following both intraleft-ventricular injection of veratridine or bradykinin, and electrical stimulation of the ipsilateral vagus nerve in an arterially perfused working heart-brainstem preparation of mouse. Administration of CP-99,994 (0.75–1.5 mg/kg i.v.), a specific NK1 antagonist, attenuated significantly the evoked reflex bradycardia and depressor response following cardiac receptor (n = 6), but not pulmonary chemoreflex stimulation in vivo. From extracellular recordings of cardioreceptive NTS neurons, CP-99,994 reduced reversibly the total number of evoked spikes, peak firing frequency and response duration evoked by intraventricular injections of veratridine (n = 5) or bradykinin (n = 5). The number of evoked action potentials following electrical stimulation of the vagus nerve was also reduced. In five whole cell recordings of NTS neurons, both the evoked depolarization following cardiac receptor stimulation, and the peak amplitude and duration of vagus nerve-evoked EPSPs were reduced by CP-99 994; synaptic inputs from both peripheral chemoreceptors or pulmonary C-fibres were unaffected. These data support a selective involvement of NK1 receptors in the transmission of cardiac vagal afferent inputs to NTS neurons integrating cardiorespiratory information.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2013
    Keywords: Respiratory network ; Ventral respiratory group ; Nucleus ambiguus ; Cardiorespiratory control ; Brainstem slice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present report describes a novel rhythmically active brainstem slice preparation that generates respiratory activity spontaneously in both mice and rats of varying maturational states. The brainstems of neonatal (0–4 days) and mature (3–8 weeks) mice and rats were isolated and a 600- to 750-μm thick slice cut to include the dorsomedial and the ventrolateral regions of the complete rostro-caudal extent of the medulla. This plane of section we have termed “tilted-sagittal”. Rhythmically discharging neurones were recorded extracellularly from both the dorsal and ventral regions of the slice. The recording sites of these neurones were found in the hypoglossal motonucleus (XII) and in areas of the ventrolateral medulla that includes the ventral respiratory group (VRG) region. Histological examination revealed the preservation of neuronal structures important for cardiorespiratory regulation and reflex control including the nucleus of the solitary tract as well as the nucleus ambiguus. In addition, pontine structures including the A5 region were also preserved. Rhythmic activity was found only in slices where the ambiguual column was preserved in its entirety. The mean frequency of discharge of XII neurones was 20 and 10 bursts per minute in neonates and mature rodents respectively. In preparations of mature animals we demonstrate that this frequency increased significantly (P〈0.05) by either raising temperature from 29°C to 38°C (54%), elevating extracellular potassium concentration from 4 to 7.5 mM (52%), blocking potassium channels (20%) or decreasing pH from 7.4 to 7.0 (18%). The burst duration to frequency ratio of XII and VRG rhythmic neurones was similar and therefore indicative of a common brainstem oscillator. Consistent with this finding was that rhythmic activity in the VRG persisted despite removal of the dorsomedial region of the slice. In contrast, rhythmic XII neurones became tonic following mechanical disconnection of the VRG.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 430 (1995), S. 115-124 
    ISSN: 1432-2013
    Keywords: Ventral respiratory group ; Phrenic nerve ; Rhythmic hypoglossal motor neurones ; Motor pattern ; In vivo ; In vitro
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The changes in motor activity of the respiratory rhythm generator were quantitatively analysed in mice (from birth to at least 56 days old) in both awake and anaesthetized preparations, as well as in vitro to define the age at which the respiratory network is mature. In awake and anaesthetized spontaneously breathing mice respiratory-related thoracic movements were recorded and revealed an age-dependent increase in both inspiratory time (45%) and cycle length (22%) over the first 15 days of life. Similarly, the pattern of phrenic nerve activity recorded from anesthetized animals also changed from a short, rapid onset and offset burst, without a post-inspiratory phase (0–10 days old), to a discharge of longer duration which included both ramp and post-inspiratory components (〉 15 days). This pattern was comparable to that seen in adult mice (〉 56 days old). A recently developed tilted-sagittal brainstem slice preparation containing an isolated, but functionally intact, medullary respiratory network was employed in our in vitro studies. Since this preparation generates respiratory rhythmic activity spontaneously in both neonatal and mature mice (〉 56 days old) it has permitted a direct comparison of the respiratory motor output pattern, recorded from the hypoglossal (XII) motor nucleus, during post-natal development in similar preparations. Consistent with our in vivo findings there was an age-dependent change in the motor pattern. The rhythmic burst of XII neurones recorded from slices of neonates (0–10 days old) was short in duration and decremented whereas a longer discharge (increase of 625% compared to neonate) containing a plateau component was seen in animals more than 15 days old. In addition, the cycle length of rhythmic XII neurones increased (143%) and, together with the changes in burst duration, reached a steady-state value over a similar time course to the maturational changes in phrenic nerve activity recorded in vivo. Our in vivo and in vitro data indicate that the central respiratory network of the mouse appears to be mature at post-natal day 15.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 434 (1997), S. 438-444 
    ISSN: 1432-2013
    Keywords: Key words Baroreceptor reflex ; Nucleus tractus solitarii ; Neonatal ; Maturation ; Cardiac vagal tone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Ontogenesis of both vagal control of heart rate and the baroreceptor vagal reflex were evaluated in rats at postnatal ages (P) of 5/6, 10, 15, 20, 25 and 〉42 days anaesthetised with urethane (1.5 g/kg). Between P5/6 and P25 heart rate rose from 372 ± 12 to 448 ± 20 beats per minute and mean arterial pressure increased from 33.9 ± 3.1 to 74.59 ± 3.25 mm Hg (mean ± SEM, n = 7 and 11 respectively). Cardiac vagal tone was absent at P10 but significant at P20 (P 〈 0.05) as revealed with atropine (0.5–1 mg/kg i.v.). Baroreceptor cardiac reflex sensitivity, tested with phenylephrine (10–50 μg/kg i.v.), was attenuated significantly in P10–20 rats compared with P5/6, P25 and mature animals. In P14–17 rats stimulation of neurones in either the solitary tract or ambiguual nuclei, by microinjection of L-glutamate (100–200 pmol), evoked an atropine-sensitive bradycardia indicating a functional integrity of central and peripheral efferent pathways mediating the baroreceptor reflex. Thus, the baroreceptor vagal reflex is functional in P5/6 rats but becomes attenuated between P10–P20, which is coincident with the maturational rise in arterial pressure.
    Type of Medium: Electronic Resource
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