scholarly journals Developmental Nicotine Exposure Alters Synaptic Input to Hypoglossal Motoneurons and Is Associated with Altered Function of Upper Airway Muscles

eNeuro ◽  
2019 ◽  
Vol 6 (6) ◽  
pp. ENEURO.0299-19.2019 ◽  
Author(s):  
Lila Buls Wollman ◽  
Jordan Clarke ◽  
Claire M. DeLucia ◽  
Richard B. Levine ◽  
Ralph F. Fregosi
Keyword(s):  
Synaptic Input ◽  
Upper Airway ◽  
Nicotine Exposure ◽  
Hypoglossal Motoneurons ◽  
Upper Airway Muscles

scholarly journals Developmental nicotine exposure alters potassium currents in hypoglossal motoneurons of neonatal rat

2017 ◽  
Vol 117 (4) ◽  
pp. 1544-1552 ◽  
Author(s):  
Marina Cholanian ◽  
Jesse Wealing ◽  
Richard B. Levine ◽  
Ralph F. Fregosi
Keyword(s):  
Synaptic Input ◽  
Potassium Currents ◽  
Neonatal Rat ◽  
Resting Potential ◽  
Extracellular Potassium ◽  
Nicotine Exposure ◽  
Whole Cell ◽  
Cell Excitability ◽  
Hypoglossal Motoneurons ◽  
Excitatory Synaptic Input

We previously showed that nicotine exposure in utero and after birth via breast milk [developmental nicotine exposure (DNE)] is associated with many changes in the structure and function of hypoglossal motoneurons (XIIMNs), including a reduction in the size of the dendritic arbor and an increase in cell excitability. Interestingly, the elevated excitability was associated with a reduction in the expression of glutamate receptors on the cell body. Together, these observations are consistent with a homeostatic compensation aimed at restoring cell excitability. Compensation for increased cell excitability could also occur by changing potassium conductance, which plays a critical role in regulating resting potential, spike threshold, and repetitive spiking behavior. Here we test the hypothesis that the previously observed increase in the excitability of XIIMNs from DNE animals is associated with an increase in whole cell potassium currents. Potassium currents were measured in XIIMNs in brain stem slices derived from DNE and control rat pups ranging in age from 0 to 4 days by whole cell patch-clamp electrophysiology. All currents were measured after blockade of action potential-dependent synaptic transmission with tetrodotoxin. Compared with control cells, XIIMNs from DNE animals showed significantly larger transient and sustained potassium currents, but this was observed only under conditions of increased cell and network excitability, which we evoked by raising extracellular potassium from 3 to 9 mM. These observations suggest that the larger potassium currents in nicotine-exposed neurons are an important homeostatic compensation that prevents “runaway” excitability under stressful conditions, when neurons are receiving elevated excitatory synaptic input. NEW & NOTEWORTHY Developmental nicotine exposure is associated with increased cell excitability, which is often accompanied by compensatory changes aimed at normalizing excitability. Here we show that whole cell potassium currents are also increased in hypoglossal motoneurons from nicotine-exposed neonatal rats under conditions of increased cell and network excitability. This is consistent with a compensatory response aimed at preventing instability under conditions in which excitatory synaptic input is high and is compatible with the concept of homeostatic plasticity.

Motor responses to positive-pressure breathing in the developing opossum

1985 ◽  
Vol 58 (5) ◽  
pp. 1489-1495 ◽  
Author(s):  
J. P. Farber
Keyword(s):  
Airway Resistance ◽  
Upper Airway ◽  
Abdominal Muscle ◽  
Positive Pressure ◽  
Postnatal Life ◽  
Abdominal Muscles ◽  
Upper Airways ◽  
Motor Responses ◽  
Upper Airway Resistance ◽  
Upper Airway Muscles

The suckling opossum exhibits an expiration-phased discharge in abdominal muscles during positive-pressure breathing (PPB); the response becomes apparent, however, only after the 3rd-5th wk of postnatal life. The purpose of this study was to determine whether the early lack of activation represented a deficiency of segmental outflow to abdominal muscles or whether comparable effects were observed in cranial outflows to muscles of the upper airways due to immaturity of afferent and/or supraspinal pathways. Anesthetized suckling opossums between 15 and 50 days of age were exposed to PPB; electromyogram (EMG) responses in diaphragm and abdominal muscles were measured, along with EMG of larynx dilator muscles and/or upper airway resistance. In animals older than approximately 30 days of age, the onset of PPB was associated with a prolonged expiration-phased EMG activation of larynx dilator muscles and/or decreased upper airway resistance, along with expiratory recruitment of the abdominal muscle EMG. These effects persisted as long as the load was maintained. Younger animals showed only those responses related to the upper airway; in fact, activation of upper airway muscles during PPB could be associated with suppression of the abdominal motor outflow. After unilateral vagotomy, abdominal and upper airway motor responses to PPB were reduced. The balance between PPB-induced excitatory and inhibitory or disfacilitory influences from the supraspinal level on abdominal motoneurons and/or spinal processing of information from higher centers may shift toward net excitation as the opossum matures.

scholarly journals Histochemical properties of upper airway muscles: comparison of dilator and nondilator muscles

1997 ◽  
Vol 10 (5) ◽  
pp. 990-993 ◽  
Author(s):  
A. Bracher ◽  
R. Coleman ◽  
R. Schnall ◽  
A. Oliven
Keyword(s):  
Upper Airway ◽  
Upper Airway Muscles

Obstructive Sleep Apnea: Epidemiology, Causes, and Consequences

2020 ◽  
Author(s):  
Diane C Lim ◽  
Richard J Schwab
Keyword(s):  
Risk Factors ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Cushing Syndrome ◽  
Upper Airway ◽  
Fat Distribution ◽  
Epidemiologic Studies ◽  
Obstructive Sleep ◽  
Upper Airway Muscles ◽  
Underlying Diseases

As part one of the three chapters on sleep-disordered breathing, this chapter reviews obstructive sleep apnea (OSA) epidemiology, causes, and consequences. When comparing OSA prevalence between 1988 to 1994 and 2007 to 2010, we observe that OSA is rapidly on the rise, paralleling increasing rates in obesity. Global epidemiologic studies indicate that there are differences specific to ethnicity with Asians presenting with OSA at a lower body mass index than Caucasians. We have learned that structural and physiologic factors increase the risk of OSA and both can be influenced by genetics. Structural risk factors include craniofacial bony restriction, changes in fat distribution, and the size of the upper airway muscles. Physiologic risk factors include airway collapsibility, loop gain, pharyngeal muscle responsiveness, and arousal threshold. The consequences of OSA include daytime sleepiness and exacerbation of many underlying diseases. OSA has been associated with cardiovascular diseases including hypertension, coronary heart disease, stroke, atrial fibrillation, and other cardiac arrhythmias; pulmonary hypertension; metabolic disorders such as type 2 diabetes, hypothyroidism, acromegaly, Cushing syndrome, and polycystic ovarian syndrome; mild cognitive impairment or dementia; and cancer. This review contains 4 figures, 1 table and 48 references. Key Words: cardiac consequences, craniofacial bony restriction, epidemiology, fat distribution, metabolic disease, neurodegeneration, obesity, obstructive sleep apnea

scholarly journals Reflex activities of the upper airway muscles during experimental nasal occlusion in anesthetized dogs.

1991 ◽  
Vol 53 (1) ◽  
pp. 93-99 ◽  
Author(s):  
Osamu KAMINUMA ◽  
Hirokazu TSUBONE ◽  
Job Manaet MATIAS ◽  
Ryohei NISHIMURA ◽  
Shigeru SUGANO
Keyword(s):  
Upper Airway ◽  
Anesthetized Dogs ◽  
Upper Airway Muscles

Respiratory muscle responses to changes in chemoreceptor drive in infants

1990 ◽  
Vol 68 (3) ◽  
pp. 1041-1047 ◽  
Author(s):  
W. A. Carlo ◽  
J. M. DiFiore
Keyword(s):  
Preterm Infants ◽  
Respiratory Muscle ◽  
Muscle Activation ◽  
Respiratory Muscles ◽  
Upper Airway ◽  
Obstructive Apnea ◽  
Surface Electrodes ◽  
Posterior Cricoarytenoid ◽  
Upper Airway Muscles ◽  
Muscle Responses

Upper airway muscles and the diaphragm may have different quantitative responses to chemoreceptor stimulation. To compare the respiratory muscle responses to changes in CO2, 10 ventilator-dependent preterm infants (gestational age 28 +/- 1 wk, postnatal age 40 +/- 6 days, weight 1.4 +/- 0.1 kg) were passively hyperventilated to apnea and subsequently hypoventilated. Electromyograms from the genioglossus, alae nasi, posterior cricoarytenoid, and diaphragm were recorded from surface electrodes. Apneic CO2 thresholds of all upper airway muscles (genioglossus 46.8 +/- 4.3 Torr, alae nasi 42.4 +/- 3.6 Torr, posterior cricoarytenoid 41.6 +/- 3.2 Torr) were higher than those of the diaphragm (38.8 +/- 2.6 Torr, all P less than 0.05). Above their CO2 threshold levels, responses of all upper airway muscles appeared proportional to those of the diaphragm. We conclude that nonproportional responses of the respiratory muscles to hypercapnia may be the result of differences in their CO2 threshold. These differences in CO2 threshold may cause imbalance in respiratory muscle activation with changes in chemical drive, leading to upper airway instability and obstructive apnea.

Arterial chemoreceptor input to respiratory hypoglossal motoneurons

1990 ◽  
Vol 69 (2) ◽  
pp. 700-709 ◽  
Author(s):  
S. W. Mifflin
Keyword(s):  
Membrane Potential ◽  
Upper Airway ◽  
Excitatory Input ◽  
Airway Patency ◽  
Hypoglossal Motoneurons ◽  
End Tidal ◽  
Carotid Body Chemoreceptors ◽  
Excitatory Drive ◽  
Arterial Chemoreceptor

To better understand the role of the arterial chemoreceptors in the regulation of upper airway patency at the level of the oropharynx, intracellular recordings were obtained from inspiratory hypoglossal motoneurons (IHMs), and the responses to selective activation of the carotid body chemoreceptors were examined. In pentobarbital-anesthetized, vagotomized, paralyzed, and artificially ventilated cats, chemoreceptor activation enhanced the inspiratory depolarization of membrane potential in 32 of 36 IHMs. This was manifested as an increase in either the amplitude (n = 13) or duration (n = 3) or an increase in both amplitude and duration (n = 16) of the inspiratory membrane potential depolarization. The amplitude and duration of the inspiratory membrane potential depolarization increased 98 +/- 15% (n = 29) and 78 +/- 13% (n = 19), respectively. Similar patterns of enhanced activity (increased duration and/or amplitude of membrane depolarization) were observed in five expiratory hypoglossal motoneurons (EHMs) after chemoreceptor activation. In 16 of the 32 IHMs, chemoreceptor activation also evoked changes in IHM membrane potential during expiration: enhanced post-inspiratory discharge (n = 6), expiratory depolarization/discharge (n = 6), and tonic depolarization/discharge, which persisted for several respiratory cycles (n = 4). The arterial chemoreceptors provide a powerful excitatory input to IHMs during both inspiration and expiration. This excitatory drive to IHMs and EHMs will aid in the maintenance of upper airway patency throughout the respiratory cycle during increases in end-tidal CO2.

scholarly journals Aging increases upper airway collapsibility in Fischer 344 rats

2008 ◽  
Vol 105 (5) ◽  
pp. 1471-1476 ◽  
Author(s):  
Andrew D. Ray ◽  
Toshiyuki Ogasa ◽  
Ulysses J. Magalang ◽  
John A. Krasney ◽  
Gaspar A. Farkas
Keyword(s):  
Neural Control ◽  
Muscle Mechanics ◽  
Upper Airway ◽  
Fischer 344 Rats ◽  
Upper Airways ◽  
Fischer 344 ◽  
Airway Collapsibility ◽  
Upper Airway Collapsibility ◽  
And Function ◽  
Upper Airway Muscles

The upper airway muscles play an important role in maintaining upper airway collapsibility, and the incidence of sleep-disordered breathing increases with age. We hypothesize that the increase in airway collapsibility with increasing age can be linked to changes in upper airway muscle mechanics and structure. Eight young (Y: 6 mo) and eight old (O: 30 mo) Fischer 344 rats were anesthetized and mechanically ventilated, and the pharyngeal pressure associated with flow limitation (Pcrit) was measured 1) with the hypoglossal (cnXII) nerve intact, 2) following bilateral cnXII denervation, and 3) during cnXII stimulation. With the cnXII intact, the upper airways of older rats were more collapsible compared with their younger counterparts [Pcrit = −7.1 ± 0.6 (SE) vs. −9.5 ± 0.7 cmH2O, respectively; P = 0.033]. CnXII denervation resulted in an increase in Pcrit such that Pcrit became similar in both groups (O: −4.2 ± 0.5 cmH2O; Y: −5.4 ± 0.5 cmH2O). In all rats, cnXII stimulation decreased Pcrit (less collapsible) in both groups (O: −11.3 ± 1.0 cmH2O; Y: −10.2 ± 1.0 cmH2O). The myosin heavy chain composition of the genioglossus muscle demonstrated a decrease in the percentage of the IIb isoform (38.3 ± 2.5 vs. 21.7 ± 1.7%; P < 0.001); in contrast, the sternohyoid muscle demonstrated an increase in the percentage of the IIb isoform (72.2 ± 2.5 vs. 58.4 ± 2.3%; P = 0.001) with age. We conclude that the upper airway becomes more collapsible with age and that the increase in upper airway collapsibility with age is likely related to altered neural control rather than to primary alterations in upper airway muscle structure and function.

scholarly journals Intensity and frequency dependence of laryngeal afferent inputs to respiratory hypoglossal motoneurons

1997 ◽  
Vol 83 (6) ◽  
pp. 1890-1899 ◽  
Author(s):  
Steven W. Mifflin
Keyword(s):  
Frequency Dependence ◽  
Stimulus Frequency ◽  
Superior Laryngeal Nerve ◽  
Upper Airway ◽  
Airway Patency ◽  
Hypoglossal Motoneurons ◽  
Afferent Fibers ◽  
Complex Motor ◽  
Afferent Inputs ◽  
Motor Acts

Mifflin, Steven W. Intensity and frequency dependence of laryngeal afferent inputs to respiratory hypoglossal motoneurons. J. Appl. Physiol. 83(6): 1890–1899, 1997.—Inspiratory hypoglossal motoneurons (IHMs) mediate contraction of the genioglossus muscle and contribute to the regulation of upper airway patency. Intracellular recordings were obtained from antidromically identified IHMs in anesthetized, vagotomized cats, and IHM responses to electrical activation of superior laryngeal nerve (SLN) afferent fibers at various frequencies and intensities were examined. SLN stimulus frequencies <2 Hz evoked an excitatory-inhibitory postsynaptic potential (EPSP-IPSP) sequence or only an IPSP in most IHMs that did not change in amplitude as the stimulus was maintained. During sustained stimulus frequencies of 5–10 Hz, there was a reduction in the amplitude of SLN-evoked IPSPs with time with variable changes in the EPSP. At stimulus frequencies >25 Hz, the amplitude of EPSPs and IPSPs was reduced over time. At a given stimulus frequency, increasing stimulus intensity enhanced the decay of the SLN-evoked postsynaptic potentials (PSPs). Frequency-dependent attenuation of SLN inputs to IHMs also occurred in newborn kittens. These results suggest that activation of SLN afferents evokes different PSP responses in IHMs depending on the stimulus frequency. At intermediate frequencies, inhibitory inputs are selectively filtered so that excitatory inputs predominate. At higher frequencies there was no discernible SLN-evoked PSP temporally locked to the SLN stimuli. Alterations in SLN-evoked PSPs could play a role in the coordination of genioglossal contraction during respiration, swallowing, and other complex motor acts where laryngeal afferents are activated.

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