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

Research output: ThesisDoctoral Thesis (compilation)

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.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical and Health Sciences

Keywords

  • systems neurophysiology, multi-channel recording, motor control, Parkinson's disease, oscillations, dyskinesia, plasticity
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
Award date2018 May 21
Place of PublicationLund
Publisher
  • Lund University, Faculty of Medicine
Print ISBNs978-91-7619-625-0
Publication statusPublished - 2018
Publication categoryResearch

Bibliographic note

Defence details Date: 2018-05-21 Time: 09:00 Place: Segerfalksalen, BMC A10, Sölvegatan 17 i Lund External reviewer(s) Name: Sharott, Andrew Title: associate professor Affiliation: University of Oxford, UK --- ISSN: 1652-8220 Lund University, Faculty of Medicine Doctoral Dissertation Series 2018:59

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Nedjeljka Ivica, Tamté, M., Ahmed, M., Ulrike Richter & Per Petersson, 2014, 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). IEEE--Institute of Electrical and Electronics Engineers Inc., p. 393-396

Research output: Chapter in Book/Report/Conference proceedingPaper in conference proceeding

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