The role of specific voltage-activated and calcium-activated potassium currents in shaping motor neuron firing output during rhythmic motor activity

Persistent Link:
http://hdl.handle.net/10150/145732
Title:
The role of specific voltage-activated and calcium-activated potassium currents in shaping motor neuron firing output during rhythmic motor activity
Author:
McKiernan, Erin Christy
Issue Date:
2010
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.
Embargo:
Embargo: Release after 6/29/2011
Abstract:
Rhythmic muscle contractions underlie a number of behaviors, such as respiration, ingestion, and locomotion, which are necessary for survival. Though in many cases motor neurons (MNs) themselves do not generate the basic motor rhythm, research suggests that the intrinsic properties of MNs may shape the timing of the final motor output. In particular, potassium (K⁺) currents can affect MN excitability and firing in a number of ways, including action potential repolarization, firing frequency, dendritic integration, repetitive firing, and burst termination. The roles played by K⁺ currents, therefore, make them ideal candidates to shape MN firing output during rhythmic activity. Just how crucial MN K⁺ currents are in shaping rhythmic motor output, which currents are crucial and what genes are responsible, and how these currents affect MN firing are areas of active investigation. Unfortunately, many previous studies attempting to answer such questions have relied on manipulations that affect large, and often unidentified, populations of neurons simultaneously. To effectively determine the role of MN currents in shaping rhythmic motor output we must target manipulations of specific ion channels to MNs. We used the Drosophila larval model system because the genetic tools available allow us to do just that. We targeted manipulations of specific calcium (Ca²⁺)-activated and voltageactivated K⁺ currents to identified populations of MNs. We hypothesized that MNs are not simply followers of network drive, but that MN firing output is further shaped during rhythmic motor activity by these K⁺ currents. Overall, our results show that though aspects of the motor output changed, such as burst duration, the system was remarkably robust in the face of K⁺ channel manipulations. Larvae expressing manipulations of the Ca²⁺-activated K⁺ channel, Slowpoke, and voltage-gated K⁺ channels Shal or eag/Shaker, continued to produce rhythmic motor output. Most manipulations had the strongest effect when expressed in cells other than just MNs, while restricting expression to smaller subsets of cells suggested that many of the effects were not intrinsic to the MNs. Even those manipulations which resulted in the strongest effects only changed burst or cycle durations by a few seconds, and did not affect the incidence or regularity of the rhythm. These results suggest that either these MN K⁺ currents minimally shape rhythmic motor output in this system, or compensation for the loss of K⁺ currents occurred. In sum, this work sheds light on the role of K⁺ currents in MNs during rhythmic activity, and points to a number of future directions examining the role of compensation in maintaining crucial rhythmic motor behaviors.
Type:
text; Electronic Dissertation
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Physiological Sciences
Degree Grantor:
University of Arizona
Advisor:
Levine, Richard; Duch, Carsten

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleThe role of specific voltage-activated and calcium-activated potassium currents in shaping motor neuron firing output during rhythmic motor activityen_US
dc.creatorMcKiernan, Erin Christyen_US
dc.contributor.authorMcKiernan, Erin Christyen_US
dc.date.issued2010-
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.releaseEmbargo: Release after 6/29/2011en_US
dc.description.abstractRhythmic muscle contractions underlie a number of behaviors, such as respiration, ingestion, and locomotion, which are necessary for survival. Though in many cases motor neurons (MNs) themselves do not generate the basic motor rhythm, research suggests that the intrinsic properties of MNs may shape the timing of the final motor output. In particular, potassium (K⁺) currents can affect MN excitability and firing in a number of ways, including action potential repolarization, firing frequency, dendritic integration, repetitive firing, and burst termination. The roles played by K⁺ currents, therefore, make them ideal candidates to shape MN firing output during rhythmic activity. Just how crucial MN K⁺ currents are in shaping rhythmic motor output, which currents are crucial and what genes are responsible, and how these currents affect MN firing are areas of active investigation. Unfortunately, many previous studies attempting to answer such questions have relied on manipulations that affect large, and often unidentified, populations of neurons simultaneously. To effectively determine the role of MN currents in shaping rhythmic motor output we must target manipulations of specific ion channels to MNs. We used the Drosophila larval model system because the genetic tools available allow us to do just that. We targeted manipulations of specific calcium (Ca²⁺)-activated and voltageactivated K⁺ currents to identified populations of MNs. We hypothesized that MNs are not simply followers of network drive, but that MN firing output is further shaped during rhythmic motor activity by these K⁺ currents. Overall, our results show that though aspects of the motor output changed, such as burst duration, the system was remarkably robust in the face of K⁺ channel manipulations. Larvae expressing manipulations of the Ca²⁺-activated K⁺ channel, Slowpoke, and voltage-gated K⁺ channels Shal or eag/Shaker, continued to produce rhythmic motor output. Most manipulations had the strongest effect when expressed in cells other than just MNs, while restricting expression to smaller subsets of cells suggested that many of the effects were not intrinsic to the MNs. Even those manipulations which resulted in the strongest effects only changed burst or cycle durations by a few seconds, and did not affect the incidence or regularity of the rhythm. These results suggest that either these MN K⁺ currents minimally shape rhythmic motor output in this system, or compensation for the loss of K⁺ currents occurred. In sum, this work sheds light on the role of K⁺ currents in MNs during rhythmic activity, and points to a number of future directions examining the role of compensation in maintaining crucial rhythmic motor behaviors.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_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.advisorLevine, Richarden_US
dc.contributor.advisorDuch, Carstenen_US
dc.contributor.committeememberFuglevand, Andrewen_US
dc.contributor.committeememberFellous, Jean-Marcen_US
dc.identifier.proquest11186-
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