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Interaction of sensory and motor signals in the basal ganglia in health and disease
KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST). Bernstein Center Freiburg, University of Freiburg, Freiburg, Germany. (The group of Prof. Jeanette Hellgren Kotaleski)ORCID iD: 0000-0002-5260-8267
2019 (English)Doctoral thesis, monograph (Other academic)
Abstract [en]

The basal ganglia, a set of deep forebrain nuclei, are among the brain regions involved in movement initiation and suppression. Although many studies have investigated the neural coding underlying these two aspects of movement, there are still questions that need to be addressed. In this thesis, I used computational models of motor thalamus and the basal ganglia at three different levels to improve the understanding of the neural coding our brain utilises to initiate and suppress movement. I used a Hodgkin-Huxley model of a thalamocortical neuron to investigate the transmission of a motor signal (i.e. movement initiation) from the basal ganglia output to the motor thalamus through post-inhibitory rebound spikes. I investigated the impact of pathological activity of the basal ganglia output (e.g. in Parkinson’s disease) and the impact of sensory responses in the basal ganglia output and cortical excitation to the thalamus on these signals. I showed that correlations in the basal ganglia output (representing pathological activity) disrupt the transmission of motor signals via rebound spikes by decreasing the signal-to-noise ratio and increasing trial-to-trial variability. In addition, I found that both the sensory responses and cortical inputs could either promote or suppress the generation of rebound spikes depending on their timing relative to the motor signal. Finally, in the model rebound spiking occurred despite the presence of moderate levels of excitation, indicating that rebound spiking might be feasible in a parameter regime relevant also in vivo.

In addition to movement initiation, I investigated the role of basal ganglia in movement suppression using a spiking network model of the basal ganglia. I simulated a stop-signal task in the model by stimulating it with realistic patterns evoking movement-related activity in the striatum and substantia nigra pars reticulata (SNr) and evoking stop-related activity in subthalamic nucleus (STN) and arkypallidal neurons in globus pallidus externa (GPe Arky). I found that a Stop response in STN delayed initiation of movement that was detected by observing SNr activity. In addition, I showed that a Stop response in GPe Arky suppressed movement-related activity in the striatum and via direct pathway in SNr. However, the pattern of these suppressed movement-related activities did not match with previous experimental observations in successful Stop trials. I explained this mismatch using a biophysically detailed multicompartmental model of projection neurons in the striatum. I found that the long-lasting depolarisations at the level of the soma, resulting from dendritic plateau potentials evoked by clustered excitatory inputs at distal dendrites, could evoke movement-related activity in these striatal neurons. The inhibition from GPe Arky targeting the excited dendrites could fully suppress the movement-related activity matching with experimental recordings in successful Stop trials.

In conclusion, the nigrothalamic model in this thesis provides novel insights into the transmission of motor signals from the basal ganglia to motor thalamus by suggesting new functional roles for active decorrelation and sensory responses in the basal ganglia, as well as cortical excitation of motor thalamus. Moreover, the simulation results of the Stop-signal task support the idea that the basal ganglia suppress movement in two steps: STN delays movement and then GPe Arky cancels movement.

Place, publisher, year, edition, pages
Stockholm: Kungliga Tekniska högskolan, 2019. , p. xix, 92
Series
TRITA-EECS-AVL ; 2019:12
National Category
Neurosciences
Research subject
Computer Science
Identifiers
URN: urn:nbn:se:kth:diva-244170ISBN: 978-91-7873-091-9 (print)OAI: oai:DiVA.org:kth-244170DiVA, id: diva2:1289507
Public defence
2019-03-13, Konstantinbågen, Drottning Kristinas väg 4 (videokonferens), Stockholm, 14:00 (English)
Opponent
Supervisors
Note

QC 20190218

Available from: 2019-02-18 Created: 2019-02-18 Last updated: 2019-02-18Bibliographically approved

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