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Basal ganglia function in genetic mouse models of Huntington's disease: a circuit-level approach
Descriptive
TitleInfo
Title
Basal ganglia function in genetic mouse models of Huntington's disease: a circuit-level approach
Name
(type = personal)
NamePart
(type = family)
Callahan
NamePart
(type = given)
Joshua W.
NamePart
(type = date)
1982-
DisplayForm
Joshua Callahan
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Tepper
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(type = given)
James
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James Tepper
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = personal)
NamePart
(type = family)
Abercrombie
NamePart
(type = given)
Elizabeth
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Elizabeth Abercrombie
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Creese
NamePart
(type = given)
Ian
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Ian Creese
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Zaborszky
NamePart
(type = given)
Laszlo
DisplayForm
Laszlo Zaborszky
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Magill
NamePart
(type = given)
Peter
DisplayForm
Peter Magill
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
outside member
Name
(type = corporate)
NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
(type = corporate)
NamePart
Graduate School - Newark
Role
RoleTerm
(authority = RULIB)
school
TypeOfResource
Text
Genre
(authority = marcgt)
theses
Genre
(authority = ExL-Esploro)
ETD doctoral
OriginInfo
DateCreated
(qualifier = exact)
2013
DateOther
(qualifier = exact);
(type = degree)
2013-10
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder that results in motor, cognitive and psychiatric abnormalities. Impairments in the processing of information between the cortex and basal ganglia are fundamental to the onset and progression of the HD phenotype. The corticosubthalamic hyperdirect pathway plays a crucial role in motor selection and blockade of neuronal activity in the STN results in a hyperkinetic movement syndrome, similar to the HD phenotype. The aim of the present study was to examine whether changes in the fidelity of information transmission between the cortex and STN emerge as a function of phenotype severity in R6/2 and YAC128 transgenic mouse models of HD. We performed in vivo extracellular recordings in the STN of anesthetized mice and measured concomitant cortical activity with electrocorticogram (ECoG) recordings during brain states that represented global cortical network synchronization or desynchronization. Dopamine (DA) can have profound effects on network synchronization between the cortex and basal ganglia and disturbances in DA transmission have been reported in HD. To monitor whether differences existed in DAergic tone in the basal ganglia we used in vivo microdialysis to measure extracellular striatal DA levels. We found in symptomatic HD transgenic mice that cortically patterned STN neuronal discharge was progressively disrupted as a function of phenotypic severity. In addition, the spontaneous activity of STN neurons was reduced in symptomatic HD transgenic mice. Stimulation of the ipsilateral cortex leads to a short latency monosynaptic excitatory response in STN neurons. Concomitant to the dissipation of STN entrainment, there was a reduction in the proportion of responsive STN neurons to cortical stimulation as a function of age. These results indicate dysfunction in the flow of information within the corticosubthalamic circuit and demonstrate progressive disconnection of the hyperdirect pathway in transgenic HD mice. Glutamatergic STN neurons provide the major excitatory drive to the output nuclei of the basal ganglia and altered discharge patterns could lead to aberrant basal ganglia output and disordered motor control.
Subject
(authority = RUETD)
Topic
Neuroscience
Subject
(authority = ETD-LCSH)
Topic
Huntington's chorea--Animal models
Subject
(authority = ETD-LCSH)
Topic
Basal ganglia--Diseases
RelatedItem
(type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - Newark Electronic Theses and Dissertations
Identifier
(type = local)
rucore10002600001
Identifier
ETD_5157
Identifier
(type = doi)
doi:10.7282/T3GT5K6B
PhysicalDescription
Form
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electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
vii, 151 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = vita)
Includes vita
Note
(type = statement of responsibility)
by Joshua W. Callahan
Location
PhysicalLocation
(authority = marcorg);
(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
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Rights
RightsDeclaration
(ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Callahan
GivenName
Joshua
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2013-10-08 03:56:23
AssociatedEntity
Name
Joshua Callahan
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - Newark
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
RULTechMD
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ContentModel
ETD
OperatingSystem
(VERSION = 5.1)
windows xp
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