Developmental Nicotine Exposure And Its Effects On Morphology And Electrophysiology Of Hypoglossal Motoneurons In The Neonatal Rat

Persistent Link:
http://hdl.handle.net/10150/337298
Title:
Developmental Nicotine Exposure And Its Effects On Morphology And Electrophysiology Of Hypoglossal Motoneurons In The Neonatal Rat
Author:
Powell, Gregory Leverette
Issue Date:
2014
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Developmental nicotine exposure (DNE) is known to cause deleterious effects in neonatal mammals through nicotine's actions on nicotinic acetylcholine receptors (nAChRs). In this work, we studied how DNE altered the structure and function of the hypoglossal motoneurons (XIIMNs) over the first few days post-parturition. Previous work in XIIMNs demonstrated an increase in cellular excitability (Pilarski et al., 2011), alterations in synaptic transmission among respiratory-related neurons (Wang et al., 2006; Pilarski et al., 2012; Jaiswal et al., 2013), and a reduction in inspiratory drive currents in DNE animals (Pilarski et al., 2011). Here we show that the effects of DNE extend to alterations in the spike-timing precision and reliability of XIIMNs, as well as spike-frequency adaptation. Additionally, simple morphological analysis of XIIMNs following nicotine exposure in utero has revealed a reduction in soma cross-sectional area. We were interested in studying the complete morphology of XIIMNs following DNE to discern its effects on more complex morphological parameters. We advanced this research using a combination of techniques in thin brainstem slices of neonatal rats, including whole cell patch clamp recordings and immunohistochemistry of intracellularly labeled hypoglossal motoneurons. Furthermore, morphological analysis revealed significant differences in the complexity of the dendritic arborization, showing that neurons from DNE animals had shorter dendrites that branched less often. We also used computational analysis to gain insight into mechanisms that may underlie the changes in spike-timing precision and reliability. In a single cell model of XIIMNs, decreases in potassium-dependent conductances such as the calcium-activated potassium current could potentially replicate the alterations seen in vitro. Finally, we also did a systems-level study of the hyoglossus muscle, a tongue retractor, to determine the relation between tongue retraction force and motor unit discharge characteristics. These experiments utilized adult, anesthetized rats to record single motor units, whole muscle electromyography (EMG) activity and tongue retraction force during spontaneous breathing. We determined that during inspiration-related tongue retractions in low and high force conditions, recruitment of motor units plays a crucial role in the control of tongue force output, whereas rate coding of single motor units is present, but appears to play a lesser role. Overall, this study shows that DNE effects the input-output properties of XIIMNs, potentially through changes in intrinsic channel properties; DNE also alters XIIMN morphology, particularly dendritic arborization; and that organization of a tongue retractor muscle depends primarily on recruitment, but also rate coding, to increase force output.
Type:
text; Electronic Dissertation
Keywords:
Development; Hypoglossal; Motoneuron; Motor Unit; Nicotine; Breathing; Physiological Sciences
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Physiological Sciences
Degree Grantor:
University of Arizona
Advisor:
Fregosi, Ralph F.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleDevelopmental Nicotine Exposure And Its Effects On Morphology And Electrophysiology Of Hypoglossal Motoneurons In The Neonatal Raten_US
dc.creatorPowell, Gregory Leveretteen_US
dc.contributor.authorPowell, Gregory Leveretteen_US
dc.date.issued2014-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractDevelopmental nicotine exposure (DNE) is known to cause deleterious effects in neonatal mammals through nicotine's actions on nicotinic acetylcholine receptors (nAChRs). In this work, we studied how DNE altered the structure and function of the hypoglossal motoneurons (XIIMNs) over the first few days post-parturition. Previous work in XIIMNs demonstrated an increase in cellular excitability (Pilarski et al., 2011), alterations in synaptic transmission among respiratory-related neurons (Wang et al., 2006; Pilarski et al., 2012; Jaiswal et al., 2013), and a reduction in inspiratory drive currents in DNE animals (Pilarski et al., 2011). Here we show that the effects of DNE extend to alterations in the spike-timing precision and reliability of XIIMNs, as well as spike-frequency adaptation. Additionally, simple morphological analysis of XIIMNs following nicotine exposure in utero has revealed a reduction in soma cross-sectional area. We were interested in studying the complete morphology of XIIMNs following DNE to discern its effects on more complex morphological parameters. We advanced this research using a combination of techniques in thin brainstem slices of neonatal rats, including whole cell patch clamp recordings and immunohistochemistry of intracellularly labeled hypoglossal motoneurons. Furthermore, morphological analysis revealed significant differences in the complexity of the dendritic arborization, showing that neurons from DNE animals had shorter dendrites that branched less often. We also used computational analysis to gain insight into mechanisms that may underlie the changes in spike-timing precision and reliability. In a single cell model of XIIMNs, decreases in potassium-dependent conductances such as the calcium-activated potassium current could potentially replicate the alterations seen in vitro. Finally, we also did a systems-level study of the hyoglossus muscle, a tongue retractor, to determine the relation between tongue retraction force and motor unit discharge characteristics. These experiments utilized adult, anesthetized rats to record single motor units, whole muscle electromyography (EMG) activity and tongue retraction force during spontaneous breathing. We determined that during inspiration-related tongue retractions in low and high force conditions, recruitment of motor units plays a crucial role in the control of tongue force output, whereas rate coding of single motor units is present, but appears to play a lesser role. Overall, this study shows that DNE effects the input-output properties of XIIMNs, potentially through changes in intrinsic channel properties; DNE also alters XIIMN morphology, particularly dendritic arborization; and that organization of a tongue retractor muscle depends primarily on recruitment, but also rate coding, to increase force output.en_US
dc.typetexten
dc.typeElectronic Dissertationen
dc.subjectDevelopmenten_US
dc.subjectHypoglossalen_US
dc.subjectMotoneuronen_US
dc.subjectMotor Uniten_US
dc.subjectNicotineen_US
dc.subjectBreathingen_US
dc.subjectPhysiological Sciencesen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorFregosi, Ralph F.en_US
dc.contributor.committeememberFregosi, Ralph F.en_US
dc.contributor.committeememberLevine, Richarden_US
dc.contributor.committeememberFuglevand, Andrewen_US
dc.contributor.committeememberFellous, Jean-Marcen_US
dc.contributor.committeememberSecomb, Timothyen_US
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