Absence of respiration modulation of carotid sinus nerve inputs to nucleus tractus solitarius neurons receiving arterial chemoreceptor inputs

In juvenile rats, the carotid body (CB) is the primary sensor of oxygen (O2) and a secondary sensor of carbon dioxide (CO2) in the blood. The CB communicates to the respiratory pattern generator via the carotid sinus nerve, which terminates within the commissural nucleus tractus solitarius (cNTS). While this is not the only peripheral chemosensory pathway in juvenile rodents, we hypothesize that it has a unique role in determining the interaction between O2 and CO2, and consequently, the response to hypoxic-hypercapnic gas challenges. The objectives of this study were to determine (1) the ventilatory responses to a poikilocapnic hypoxic (HX) gas challenge, a hypercapnic (HC) gas challenge or a hypoxic-hypercapnic (HH) gas challenge in juvenile rats; and (2) the roles of CSN chemoafferents in the interactions between HX and HC signaling in these rats. Studies were performed on conscious, freely moving juvenile (P25) male Sprague Dawley rats that underwent sham-surgery (SHAM) or bilateral transection of the carotid sinus nerves (CSNX) 4 days previously. Rats were placed in whole-body plethysmographs to record ventilatory parameters (frequency of breathing, tidal volume and minute ventilation). After acclimatization, they were exposed to HX (10% O2, 90% N2), HC (5% CO2, 21% O2, 74% N2) or HH (5% CO2, 10% O2, 85% N2) gas challenges for 5 min, followed by 15 min of room-air. The major findings were: (1) the HX, HC and HH challenges elicited robust ventilatory responses in SHAM rats; (2) ventilatory responses elicited by HX alone and HC alone were generally additive in SHAM rats; (3) the ventilatory responses to HX, HC and HH were markedly attenuated in CSNX rats compared to SHAM rats; and (4) ventilatory responses elicited by HX alone and HC alone were not additive in CSNX rats. Although the rats responded to HX after CSNX, CB chemoafferent input was necessary for the response to HH challenge. Thus, secondary peripheral chemoreceptors do not compensate for the loss of chemoreceptor input from the CB in juvenile rats.

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Chronic hypoxia enhances the phrenic nerve response to arterial chemoreceptor stimulation in anesthetized rats

Journal of Applied Physiology ◽

10.1152/jappl.1999.87.2.817 ◽

1999 ◽

Vol 87 (2) ◽

pp. 817-823 ◽

Cited By ~ 83

Author(s):

M. R. Dwinell ◽

F. L. Powell

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Phrenic Nerve ◽

Chronic Hypoxia ◽

Carotid Sinus ◽

Carotid Sinus Nerve ◽

Nerve Activity ◽

Phrenic Nerve Activity ◽

Hypoxic Group ◽

Arterial Chemoreceptor

Chronic exposure to hypoxia results in a time-dependent increase in ventilation called ventilatory acclimatization to hypoxia. Increased O2 sensitivity of arterial chemoreceptors contributes to ventilatory acclimatization to hypoxia, but other mechanisms have also been hypothesized. We designed this experiment to determine whether central nervous system processing of peripheral chemoreceptor input is affected by chronic hypoxic exposure. The carotid sinus nerve was stimulated supramaximally at different frequencies (0.5–20 Hz, 0.2-ms duration) during recording of phrenic nerve activity in two groups of anesthetized, ventilated, vagotomized rats. In the chronically hypoxic group (7 days at 80 Torr inspired [Formula: see text]), phrenic burst frequency (fR, bursts/min) was significantly higher than in the normoxic control group with carotid sinus nerve stimulation frequencies >5 Hz. In the chronically hypoxic group, peak amplitude of integrated phrenic nerve activity ( ∫ Phr, percent baseline) or change in ∫ Phr was significantly greater at stimulation frequencies between 5 and 17 Hz, and minute phrenic activity ( ∫ Phr × fR) was significantly greater at stimulation frequencies >5 Hz. These experiments show that chronic hypoxia facilitates the translation of arterial chemoreceptor afferent input to ventilatory efferent output through a mechanism in the central nervous system.

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A GABA-mediated inhibition of neurones in the nucleus tractus solitarius of the cat that respond to electrical stimulation of the carotid sinus nerve

Neuroscience Letters ◽

10.1016/0304-3940(88)90038-9 ◽

1988 ◽

Vol 94 (3) ◽

pp. 321-326 ◽

Cited By ~ 32

Author(s):

Peter N. McWilliam ◽

Sara L. Shepheard

Keyword(s):

Electrical Stimulation ◽

Carotid Sinus ◽

Nucleus Tractus Solitarius ◽

Carotid Sinus Nerve ◽

Stimulation Of

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Integration-differentiation and gating of carotid afferent traffic that shapes the respiratory pattern

Journal of Applied Physiology ◽

10.1152/japplphysiol.00639.2002 ◽

2003 ◽

Vol 94 (3) ◽

pp. 1213-1229 ◽

Cited By ~ 25

Author(s):

Daniel L. Young ◽

Frederick L. Eldridge ◽

Chi-Sang Poon

Keyword(s):

Carotid Sinus ◽

Nucleus Tractus Solitarius ◽

Respiratory Rhythm ◽

Respiratory Pattern ◽

Carotid Sinus Nerve ◽

Short Term ◽

Time Frequency ◽

Disease States ◽

Stop And Go ◽

Term Potentiation

The phase-dependent plasticity of carotid chemoafferent signaling was studied with electrical stimulation of a carotid sinus nerve during either inspiration or expiration in anesthetized, glomectomized, vagotomized, paralyzed, and ventilated rats. Stroboscopic and interferometric analyses of the resulting phase-contrast disturbances of the respiratory rhythm revealed that carotid chemoafferent traffic was dynamically filtered centrally by a parallel bank of leaky integrators and differentiators, each being logically gated to the inspiratory or expiratory phase in a stop-and-go manner as follows: 1) carotid short-term potentiation of inspiratory drive was mediated by dual integrators that both shortened inspiration and augmented phrenic motor output cooperatively in long and short timescales; 2) carotid short-term depression of respiratory frequency was mediated by a (possibly pontine) integrator that lengthened expiration with a relatively long memory; and 3) carotid “chemoreflex” shortening of expiration was mediated by an occult fast integrator, which, together with carotid short-term depression, formed a differentiator. These effects were modulated anteriorly by integrators in the nucleus tractus solitarius that were “auto-gated” to, or recruited by, the carotid sinus nerve input. Such phase-selective and activity-dependent time-frequency filtering of carotid chemoafferent feedback in parallel neurological-neurodynamic central pathways may profoundly affect respiratory stability during hypoxia and sleep and could contribute to the dynamic optimization of the respiratory pattern and maintenance of homeostasis in health and in disease states.

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Interactions in nucleus tractus solitarius between right and left carotid sinus nerves

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1987.253.5.h1127 ◽

1987 ◽

Vol 253 (5) ◽

pp. H1127-H1135 ◽

Cited By ~ 3

Author(s):

R. B. Felder ◽

C. M. Heesch

Keyword(s):

Carotid Sinus ◽

Nucleus Tractus Solitarius ◽

Conditioning Stimulus ◽

Afferent Input ◽

Primary Afferent Depolarization ◽

Carotid Sinus Nerve ◽

Inhibitory Interaction ◽

Bilateral Carotid ◽

Carotid Sinus Nerve Stimulation ◽

Stimulation Of

Bilateral carotid sinus nerve stimulation was used as a model for studying cardiovascular afferent interactions in the nucleus tractus solitarius (NTS) region of dorso-medial medulla. Extracellular action potential recordings were made from 69 single units, 33 of which were excited independently by both right and left carotid sinus nerves (CSNs). Fifteen of these were located in NTS. Peak latencies to electrical stimulation of NTS neurons were 17.7 +/- 2.1 ms to ipsilateral CSN and 20.9 +/- 1.5 ms to contralateral CSN. Summation of afferent input was routinely demonstrated. In 10 units in NTS, a conditioning stimulus applied to one CSN caused prolonged inhibition of the response to a test stimulus to the same or the other CSN. The duration of inhibition was dependent on the intensity of the conditioning stimulus, not on prior excitation of the unit by the conditioning stimulus. In five additional excitability testing experiments, we found limited evidence to suggest that primary afferent depolarization of the central fibers of one CSN by stimulation of the contralateral CSN might be contributing to this inhibitory interaction. The data suggest that the outcome of integrative interactions between right and left CSN inputs to NTS neurons may depend largely on the temporal sequence of convergent afferent impulses.

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Arterial chemoreceptor input to nucleus tractus solitarius

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.263.2.r368 ◽

1992 ◽

Vol 263 (2) ◽

pp. R368-R375 ◽

Cited By ~ 46

Author(s):

S. W. Mifflin

Keyword(s):

Carotid Body ◽

Carotid Sinus ◽

Nucleus Tractus Solitarius ◽

Excitatory Input ◽

Inhibitory Input ◽

Mechanically Ventilated ◽

The Central Nervous System ◽

Carotid Body Chemoreceptors ◽

Two Peaks ◽

Arterial Chemoreceptor

The arterial chemoreceptors play an important role in the reflex regulation of blood pressure and respiration. To investigate the initial integration of chemoreceptor inputs within the central nervous system, intracellular recordings were obtained in pentobarbital-anesthetized, paralyzed, and mechanically ventilated cats, from 58 cells within the nucleus of the tractus solitarius (NTS) that were depolarized by activation of the ipsilateral carotid body chemoreceptors. Close arterial injection of less than 100 microliters CO2-saturated bicarbonate evoked depolarizations of membrane potential with amplitudes of 2.2-4.6 mV and durations of 1.8-6.7 s in 46 cells. In 12 cells, activation of the carotid body chemoreceptors evoked a depolarization-hyperpolarization sequence. Electrical stimulation of the carotid sinus nerve (500 microA, 0.2 ms) evoked EPSPs [mean latency 6.4 +/- 0.5 (SE) ms; range 2.1-18.4 ms] in 46 cells and EPSP-IPSPs (7.3 +/- 0.8 ms; range 4.2-12.4 ms) in 12 cells. The distribution of EPSP latencies exhibited two peaks, one in the 2- to 4-ms range and another in the 7- to 8-ms range. Twenty-nine chemoreceptive cells were tested for the presence of convergent inputs from the ipsilateral carotid sinus baroreceptors. No evidence was found of a convergent postsynaptic inhibitory input from the baroreceptors within the NTS; however, seven cells were found that received an excitatory input from the baroreceptors. The observation that NTS neurons do not integrate chemoreceptor afferent inputs in a homogeneous manner suggests that the multiplicity of NTS unit responses might be related to the specific reflex function of an individual cell (e.g., vagal or sympathetic outflow, respiration).(ABSTRACT TRUNCATED AT 250 WORDS)

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