The Role of the Cortico-Basal Ganglia-System in Voluntary Movements
Author
Summary, in English
Bodies with multiple limbs and joints have endless possibilities to move around in their surrounding space. How the nervous system controls this amount of degrees of freedom in motor execution is a question under vigorous debate. In an ambition to explore related aspects of motor control we conducted parallel electrophysiological recordings of motor circuits in the cortex and basal ganglia in the consciously behaving rodent during the execution of various motor behaviors.
To be able to further explore the relevance of neuronal activation patterns for different behaviours within these motor structures, we developed two methods - one focusing on increasing the amount of information acquired from the neuronal recordings and the other on improved motion tracking. The first method enabled a flexible electrode construction for targeting of multiple regions of the brain simultaneously. In the motion tracking system an anatomically defined model of the rodent paw was developed. With high resolution recordings a detailed reconstruction of a complex movement permitted differentiation of multiple kinematic parameters that could be related to the electrophysiological recordings. In experiments employing a reach and grasp paradigm, we were able to correlate the neuronal code to a previously suggested subdivision of the compound movement into functional sub-components, in effect validating the method.
In further studies we utilized the 6-OHDA rodent model of Parkinson’s disease, where motor control is impaired. Here we found that levodopa induced-dyskinesia was tightly associated with a strong oscillatory phenomenon in the motor cortex, and that stopping the oscillation locally was sufficient for alleviation of motor symptoms. By expanding the neuronal recordings using the developed electrode we showed that different states of the disease could be reliably discerned. When comparing these disease states with a control state, we could thus assess the effect of drugs in their ability to normalize disease-relevant signals. The validity of this procedure was verified by correlation between the behavioral and neuronal measures. These experiments demonstrate that neuronal measures of internal states can be utilized for evaluation of new treatment strategies and have a high potential in aiding drug development for diseases without clear behavioral phenotypes.
To be able to further explore the relevance of neuronal activation patterns for different behaviours within these motor structures, we developed two methods - one focusing on increasing the amount of information acquired from the neuronal recordings and the other on improved motion tracking. The first method enabled a flexible electrode construction for targeting of multiple regions of the brain simultaneously. In the motion tracking system an anatomically defined model of the rodent paw was developed. With high resolution recordings a detailed reconstruction of a complex movement permitted differentiation of multiple kinematic parameters that could be related to the electrophysiological recordings. In experiments employing a reach and grasp paradigm, we were able to correlate the neuronal code to a previously suggested subdivision of the compound movement into functional sub-components, in effect validating the method.
In further studies we utilized the 6-OHDA rodent model of Parkinson’s disease, where motor control is impaired. Here we found that levodopa induced-dyskinesia was tightly associated with a strong oscillatory phenomenon in the motor cortex, and that stopping the oscillation locally was sufficient for alleviation of motor symptoms. By expanding the neuronal recordings using the developed electrode we showed that different states of the disease could be reliably discerned. When comparing these disease states with a control state, we could thus assess the effect of drugs in their ability to normalize disease-relevant signals. The validity of this procedure was verified by correlation between the behavioral and neuronal measures. These experiments demonstrate that neuronal measures of internal states can be utilized for evaluation of new treatment strategies and have a high potential in aiding drug development for diseases without clear behavioral phenotypes.
Department/s
Publishing year
2016
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2016:37
Full text
- Available as PDF - 54 MB
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Document type
Dissertation
Publisher
Integrative Neurophysiology, Lund University
Topic
- Neurosciences
Keywords
- Neurophysiology
- Electrophysiology
- Pharmacology
- Motor Systems
- Voluntary movements
- Philosophy
- In vivo
- Corticostriatal
- Parkinson's disease
- Dyskinesia
- Levodopa
- Multiple Electrode Arrays
Status
Published
Research group
- Integrative Neurophysiology
- Neuronano Research Center (NRC)
Supervisor
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-7619-263-4
Defence date
31 March 2016
Defence time
09:00
Defence place
Lecture hall, Pufendorf institute, Biskopsgatan 3 i Lund
Opponent
- Judith Walters (Professor)