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Article ; Online: Chronic, episodic nicotine exposure alters GABAergic synaptic transmission to hypoglossal motor neurons and genioglossus muscle function at a critical developmental age.

Wollman, Lila Buls / Flanigan, Emily Gayle / Fregosi, Ralph F

2022 Volume 128, Issue 6, Page(s) 1483–1500

Abstract: Regulation of GABAergic signaling through nicotinic acetylcholine receptor (nAChR) activation is critical for neuronal development. Here, we test the hypothesis that chronic episodic developmental nicotine exposure (eDNE) disrupts GABAergic signaling, ... ...

Abstract	Regulation of GABAergic signaling through nicotinic acetylcholine receptor (nAChR) activation is critical for neuronal development. Here, we test the hypothesis that chronic episodic developmental nicotine exposure (eDNE) disrupts GABAergic signaling, leading to dysfunction of hypoglossal motor neurons (XIIMNs), which innervate the tongue muscles. We studied control and eDNE pups at two developmentally vulnerable age ranges: postnatal days (P)1-5 and P10-12. The amplitude and frequency of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs, mIPSCs) at baseline were not altered by eDNE at either age. In contrast, eDNE increased GABA
MeSH term(s)	Humans ; Rats ; Animals ; Infant, Newborn ; Nicotine/pharmacology ; Muscimol/pharmacology ; Animals, Newborn ; Rats, Sprague-Dawley ; Synaptic Transmission/physiology ; Motor Neurons/physiology ; Tongue ; Muscles
Chemical Substances	Nicotine (6M3C89ZY6R) ; Muscimol (2763-96-4)
Language	English
Publishing date	2022-11-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00397.2022
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Article ; Online: A tribute to Charles M. "Tip" Tipton (1927-2021).

Dempsey, Jerome A / Fregosi, Ralph F / Booth, Frank W

Journal of applied physiology (Bethesda, Md. : 1985)

2021 Volume 131, Issue 1, Page(s) 192–193

MeSH term(s)	Cardiac Output ; Stroke Volume
Language	English
Publishing date	2021-06-03
Publishing country	United States
Document type	Editorial
ZDB-ID	219139-8
ISSN	1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
ISSN (online)	1522-1601
ISSN	0021-8987 ; 0161-7567 ; 8750-7587
DOI	10.1152/japplphysiol.00370.2021
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Article ; Online: A homemade device for simultaneous measurement of pulmonary ventilation and metabolic rate in neonatal rodents.

Boyd, Brennan / Hoyer-Kimura, Christina / Wollman, Lila / Fregosi, Ralph F

Respiratory physiology & neurobiology

2022 Volume 299, Page(s) 103858

Abstract: Various in vitro neonatal rodent models have been developed to study the control of breathing, but translation of the information requires a behavioral assay, which has led to the widespread use of plethysmography to measure breathing in awake neonatal ... ...

Abstract	Various in vitro neonatal rodent models have been developed to study the control of breathing, but translation of the information requires a behavioral assay, which has led to the widespread use of plethysmography to measure breathing in awake neonatal rodents. Best practice requires correcting changes in ventilation to the corresponding change in metabolic rate, which is the main driver of pulmonary ventilation. Obtaining measures of both simultaneously is ideal, though technically difficult. Here we describe a simple, inexpensive home-made dual chamber approach for simultaneous measurement of pulmonary ventilation and metabolic rate. We found that the dual chamber provides values for pulmonary ventilation and metabolic rate that compare favorably with existing approaches.
MeSH term(s)	Animals ; Lung ; Plethysmography ; Pulmonary Ventilation ; Respiration ; Rodentia
Language	English
Publishing date	2022-01-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2077867-3
ISSN	1878-1519 ; 1569-9048
ISSN (online)	1878-1519
ISSN	1569-9048
DOI	10.1016/j.resp.2022.103858
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Article ; Online: Chronic, Episodic Nicotine Alters Hypoglossal Motor Neuron Function at a Critical Developmental Time Point in Neonatal Rats.

Buls Wollman, Lila / Fregosi, Ralph F

eNeuro

2021 Volume 8, Issue 4

Abstract: Developmental nicotine exposure (DNE), alters brainstem neurons that control breathing, including hypoglossal motor neurons (XIIMNs), which innervate the tongue. Here, we tested the hypothesis that chronic, episodic DNE (eDNE), which mimics nicotine ... ...

Abstract	Developmental nicotine exposure (DNE), alters brainstem neurons that control breathing, including hypoglossal motor neurons (XIIMNs), which innervate the tongue. Here, we tested the hypothesis that chronic, episodic DNE (eDNE), which mimics nicotine replacement therapies such as e-cigarettes or nicotine gum, alters the function of nicotinic acetylcholine receptors (nAChRs), XIIMN intrinsic properties, and tongue muscle function
MeSH term(s)	Animals ; Animals, Newborn ; Electronic Nicotine Delivery Systems ; Female ; Hypoglossal Nerve ; Motor Neurons ; Nicotine ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley ; Receptors, Nicotinic ; Smoking Cessation ; Tobacco Use Cessation Devices
Chemical Substances	Receptors, Nicotinic ; Nicotine (6M3C89ZY6R)
Language	English
Publishing date	2021-08-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2800598-3
ISSN	2373-2822 ; 2373-2822
ISSN (online)	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0203-21.2021
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Article ; Online: Reply to Drs. Nuzzo and Barry.

Fregosi, Ralph F / Wagner, Peter D

Journal of applied physiology (Bethesda, Md. : 1985)

2017 Volume 123, Issue 5, Page(s) 1421

MeSH term(s)	Humans ; Resistance Training
Language	English
Publishing date	2017-11-22
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	219139-8
ISSN	1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
ISSN (online)	1522-1601
ISSN	0021-8987 ; 0161-7567 ; 8750-7587
DOI	10.1152/japplphysiol.00599.2017
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Article ; Online: When negative is positive.

Fregosi, Ralph F / Wagner, Peter D

Journal of applied physiology (Bethesda, Md. : 1985)

2016 Volume 121, Issue 3, Page(s) 605

MeSH term(s)	Biomedical Research/trends ; Humans ; Muscle Strength ; Muscle, Skeletal/physiology ; Resistance Training
Language	English
Publishing date	2016-08-11
Publishing country	United States
Document type	Editorial
ZDB-ID	219139-8
ISSN	1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
ISSN (online)	1522-1601
ISSN	0021-8987 ; 0161-7567 ; 8750-7587
DOI	10.1152/japplphysiol.00708.2016
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Article ; Online: Muscles of Breathing: Development, Function, and Patterns of Activation.

Pilarski, Jason Q / Leiter, James C / Fregosi, Ralph F

Comprehensive Physiology

2019 Volume 9, Issue 3, Page(s) 1025–1080

Abstract: This review is a comprehensive description of all muscles that assist lung inflation or deflation in any way. The developmental origin, anatomical orientation, mechanical action, innervation, and pattern of activation are described for each respiratory ... ...

Abstract	This review is a comprehensive description of all muscles that assist lung inflation or deflation in any way. The developmental origin, anatomical orientation, mechanical action, innervation, and pattern of activation are described for each respiratory muscle fulfilling this broad definition. In addition, the circumstances in which each muscle is called upon to assist ventilation are discussed. The number of "respiratory" muscles is large, and the coordination of respiratory muscles with "nonrespiratory" muscles and in nonrespiratory activities is complex-commensurate with the diversity of activities that humans pursue, including sleep (8.27). The capacity for speech and adoption of the bipedal posture in human evolution has resulted in patterns of respiratory muscle activation that differ significantly from most other animals. A disproportionate number of respiratory muscles affect the nose, mouth, pharynx, and larynx, reflecting the vital importance of coordinated muscle activity to control upper airway patency during both wakefulness and sleep. The upright posture has freed the hands from locomotor functions, but the evolutionary history and ontogeny of forelimb muscles pervades the patterns of activation and the forces generated by these muscles during breathing. The distinction between respiratory and nonrespiratory muscles is artificial, as many "nonrespiratory" muscles can augment breathing under conditions of high ventilator demand. Understanding the ontogeny, innervation, activation patterns, and functions of respiratory muscles is clinically useful, particularly in sleep medicine. Detailed explorations of how the nervous system controls the multiple muscles required for successful completion of respiratory behaviors will continue to be a fruitful area of investigation. © 2019 American Physiological Society. Compr Physiol 9:1025-1080, 2019.
MeSH term(s)	Animals ; Fetal Development/physiology ; Humans ; Mesoderm/anatomy & histology ; Recruitment, Neurophysiological/physiology ; Respiratory Mechanics/physiology ; Respiratory Muscles/anatomy & histology ; Respiratory Muscles/embryology ; Respiratory Muscles/innervation ; Respiratory Muscles/physiology ; Respiratory System/anatomy & histology ; Sleep/physiology ; Wakefulness/physiology
Language	English
Publishing date	2019-06-12
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2040-4603
ISSN (online)	2040-4603
DOI	10.1002/cphy.c180008
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Article ; Online: Respiratory related control of hypoglossal motoneurons--knowing what we do not know.

Fregosi, Ralph F

Respiratory physiology & neurobiology

2011 Volume 179, Issue 1, Page(s) 43–47

Abstract: Because tongue position and stiffness help insure that the pharyngeal airspace is sufficiently open during breathing, the respiration-related behavior of the tongue muscles has been studied in detail, particularly during the last two decades. Although ... ...

Abstract	Because tongue position and stiffness help insure that the pharyngeal airspace is sufficiently open during breathing, the respiration-related behavior of the tongue muscles has been studied in detail, particularly during the last two decades. Although eight different muscles act upon the mammal tongue, we know very little about the respiration-related control of the majority of these, and almost nothing about how they work together as a complex electro-mechanical system. Other significant gaps include how hypoglossal motoneuron axons find their appropriate muscle target during development, whether the biophysical properties of hypoglossal motoneurons driving different muscles are the same, and how afferent information from cardiorespiratory reflex systems is transmitted from major brainstem integrating centers to the hypoglossal motoneuron pool. This brief review outlines some of these issues, with the hope that this will spur research in the field, ultimately leading to an improved understanding of the respiration-related control of the mammalian tongue musculature.
MeSH term(s)	Animals ; Humans ; Hypoglossal Nerve/cytology ; Hypoglossal Nerve/physiology ; Motor Neurons/physiology ; Pharyngeal Muscles/innervation ; Pharyngeal Muscles/physiology ; Respiratory Mechanics/physiology
Language	English
Publishing date	2011-07-02
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2077867-3
ISSN	1878-1519 ; 1569-9048
ISSN (online)	1878-1519
ISSN	1569-9048
DOI	10.1016/j.resp.2011.06.023
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Article ; Online: Influence of tongue muscle contraction and transmural pressure on nasopharyngeal geometry in the rat.

Fregosi, Ralph F

Journal of applied physiology (Bethesda, Md. : 1985)

2011 Volume 111, Issue 3, Page(s) 766–774

Abstract: The mammalian pharynx is a hollow muscular tube that participates in ingestion and respiration, and its size, shape, and stiffness can be altered by contraction of skeletal muscles that lie inside or outside of its walls. MRI was used to determine the ... ...

Abstract	The mammalian pharynx is a hollow muscular tube that participates in ingestion and respiration, and its size, shape, and stiffness can be altered by contraction of skeletal muscles that lie inside or outside of its walls. MRI was used to determine the interaction between pharyngeal pressure and selective stimulation of extrinsic tongue muscles on the shape of the rat nasopharynx. Pressure (-9, -6, -3, 3, 6, and 9 cmH₂O) was applied randomly to the isolated pharyngeal airway of anesthetized rats that were positioned in a 4.7-T MRI scanner. The anterior-posterior (AP) and lateral diameters of the nasopharynx were measured in eight axial slices at each level of pressure, with and without bilateral hypoglossal nerve stimulation (0.1-ms pulse, 1/3 maximal force, 80 Hz). The rat nasopharynx is nearly circular, and positive pharyngeal pressure caused similar expansion of AP and lateral diameters; as a result, airway shape (ratio of lateral to AP diameter) remained constant. Negative pressure did not change AP or lateral diameter significantly, suggesting that a negative pressure reflex activated the tongue or other pharyngeal muscles. Stimulation of tongue protrudor muscles alone or coactivation of protrudor and retractor muscles caused greater AP than lateral expansion, making the nasopharynx slightly more elliptical, with the long axis in the AP direction. These effects tended to be more pronounced at negative pharyngeal pressures and greater in the caudal than rostral nasopharynx. These data show that stimulation of rodent tongue muscles can adjust pharyngeal shape, extending previous work showing that tongue muscle contraction alters pharyngeal compliance and volume, and provide physiological insight that can be applied to the treatment of obstructive sleep apnea.
MeSH term(s)	Animals ; Biomechanical Phenomena ; Electric Stimulation ; Hypoglossal Nerve/physiology ; Magnetic Resonance Imaging ; Male ; Muscle Contraction ; Muscle, Skeletal/innervation ; Muscle, Skeletal/physiology ; Nasopharynx/anatomy & histology ; Pressure ; Rats ; Rats, Sprague-Dawley ; Reflex ; Tongue/innervation ; Tongue/physiology
Language	English
Publishing date	2011-06-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	219139-8
ISSN	1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
ISSN (online)	1522-1601
ISSN	0021-8987 ; 0161-7567 ; 8750-7587
DOI	10.1152/japplphysiol.01501.2010
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Article ; Online: Influence of developmental nicotine exposure on serotonergic control of breathing-related motor output.

Wollman, Lila / Hill, Andrew / Hasse, Brady / Young, Christina / Hernandez-De La Pena, Giovanni / Levine, Richard B / Fregosi, Ralph F

Developmental neurobiology

2022 Volume 82, Issue 2, Page(s) 175–191

Abstract: Serotonin plays an important role in the development of brainstem circuits that control breathing. Here, we test the hypothesis that developmental nicotine exposure (DNE) alters the breathing-related motor response to serotonin (5HT). Pregnant rats were ... ...

Abstract	Serotonin plays an important role in the development of brainstem circuits that control breathing. Here, we test the hypothesis that developmental nicotine exposure (DNE) alters the breathing-related motor response to serotonin (5HT). Pregnant rats were exposed to nicotine or saline, and brainstem-spinal cord preparations from 1- to 5-day-old pups were studied in a split-bath configuration, allowing drugs to be applied selectively to the medulla or spinal cord. The activity of the fourth cervical ventral nerve roots (C4VR), which contain axons of phrenic motoneurons, was recorded. We applied 5HT alone or together with antagonists of 5HT1A, 5HT2A, or 5HT7 receptor subtypes. In control preparations, 5HT applied to the medulla consistently reduced C4VR frequency and this reduction could not be blocked by any of the three antagonists. In DNE preparations, medullary 5HT caused a large and sustained frequency increase (10 min), followed by a sustained decrease. Notably, the transient increase in frequency could be blocked by the independent addition of any of the antagonists. Experiments with subtype-specific agonists suggest that the 5HT7 subtype may contribute to the increased frequency response in the DNE preparations. Changes in C4VR burst amplitude in response to brainstem 5HT were uninfluenced by DNE. Addition of 5HT to the caudal chamber modestly increased phasic and greatly increased tonic C4VR activity, but there were no effects of DNE. The data show that DNE alters serotonergic signaling within brainstem circuits that control respiratory frequency but does not functionally alter serotonin signaling in the phrenic motoneuron pool.
MeSH term(s)	Animals ; Animals, Newborn ; Female ; Nicotine/pharmacology ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley ; Synaptic Transmission/physiology
Chemical Substances	Nicotine (6M3C89ZY6R)
Language	English
Publishing date	2022-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2256184-5
ISSN	1932-846X ; 1097-4695 ; 1932-8451 ; 0022-3034
ISSN (online)	1932-846X ; 1097-4695
ISSN	1932-8451 ; 0022-3034
DOI	10.1002/dneu.22866
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