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Circuit-level analyses of cortico-basal ganglia-thalamic networks. Effects of dopamine dysregulation and experience dependent plasticity.

Ivica, Nedjeljka LU (2018)
Abstract
The cortico-basal ganglia-thalamic (CBT) circuit is thought to be involved in control of voluntary and goal-directed movements and action selection. Dopamine is known to play a crucial role in this circuit and regulating its activity. The important role of dopamine is particularly evident in Parkinson’s patients, where dopaminergic cells are dying and motor impairments follow. While dopamine replacement is an effective therapy, satisfactory alleviation only lasts for a limited number of years, after which patients frequently develop side-effects in the form of levodopa-induced dyskinesia. In order to clarify the neurophysiological consequences of dopamine dysregulation we have here investigated the electrophysiological activity of each... (More)
The cortico-basal ganglia-thalamic (CBT) circuit is thought to be involved in control of voluntary and goal-directed movements and action selection. Dopamine is known to play a crucial role in this circuit and regulating its activity. The important role of dopamine is particularly evident in Parkinson’s patients, where dopaminergic cells are dying and motor impairments follow. While dopamine replacement is an effective therapy, satisfactory alleviation only lasts for a limited number of years, after which patients frequently develop side-effects in the form of levodopa-induced dyskinesia. In order to clarify the neurophysiological consequences of dopamine dysregulation we have here investigated the electrophysiological activity of each part of the CBT-loop in rats during different experimental conditions, using custom made multi-channel electrodes. Neuronal activity changes in 16 CBT structures were characterized upon acute pharmacological dopaminergic manipulations and firing rate changes of subgroup of cells within different structures in the CBT circuit were shown to potentially be responsible for the severe akinesia induced by the drugs. We have also developed a novel method to monitor the global state of the CBT circuit in a rat model of levodopa-induced dyskinesia and showed how this approach can be used to help developing new pharmacological therapies. Lastly, to investigate how somatosensory input is affecting motor circuits, we have recorded activity of the whole CBT-loop in rats before and after extensive skilled forelimb reaching and grasping training. Preliminary results show that only the motor cortex display experience-dependent changes due to the reaching training. (Less)
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author
supervisor
opponent
  • associate professor Sharott, Andrew, University of Oxford, UK
organization
publishing date
type
Thesis
publication status
published
subject
keywords
systems neurophysiology, multi-channel recording, motor control, Parkinson's disease, oscillations, dyskinesia, plasticity
pages
103 pages
publisher
Lund University, Faculty of Medicine
defense location
Segerfalksalen, BMC A10, Sölvegatan 17 i Lund
defense date
2018-05-21 09:00
ISBN
978-91-7619-625-0
language
English
LU publication?
yes
id
75714f5b-bf16-4de3-9f21-3b7848c4820d
date added to LUP
2018-05-01 10:58:38
date last changed
2018-11-21 21:39:38
@phdthesis{75714f5b-bf16-4de3-9f21-3b7848c4820d,
  abstract     = {The cortico-basal ganglia-thalamic (CBT) circuit is thought to be involved in control of voluntary and goal-directed movements and action selection. Dopamine is known to play a crucial role in this circuit and regulating its activity. The important role of dopamine is particularly evident in Parkinson’s patients, where dopaminergic cells are dying and motor impairments follow. While dopamine replacement is an effective therapy, satisfactory alleviation only lasts for a limited number of years, after which patients frequently develop side-effects in the form of levodopa-induced dyskinesia. In order to clarify the neurophysiological consequences of dopamine dysregulation we have here investigated the electrophysiological activity of each part of the CBT-loop in rats during different experimental conditions, using custom made multi-channel electrodes. Neuronal activity changes in 16 CBT structures were characterized upon acute pharmacological dopaminergic manipulations and firing rate changes of subgroup of cells within different structures in the CBT circuit were shown to potentially be responsible for the severe akinesia induced by the drugs. We have also developed a novel method to monitor the global state of the CBT circuit in a rat model of levodopa-induced dyskinesia and showed how this approach can be used to help developing new pharmacological therapies. Lastly, to investigate how somatosensory input is affecting motor circuits, we have recorded activity of the whole CBT-loop in rats before and after extensive skilled forelimb reaching and grasping training. Preliminary results show that only the motor cortex display experience-dependent changes due to the reaching training.},
  author       = {Ivica, Nedjeljka},
  isbn         = {978-91-7619-625-0},
  keyword      = {systems neurophysiology,multi-channel recording,motor control,Parkinson's disease,oscillations,dyskinesia,plasticity},
  language     = {eng},
  pages        = {103},
  publisher    = {Lund University, Faculty of Medicine},
  school       = {Lund University},
  title        = {Circuit-level analyses of cortico-basal ganglia-thalamic networks. Effects of dopamine dysregulation and experience dependent plasticity.},
  year         = {2018},
}