Mean-field modeling of the basal ganglia-thalamocortical system. I Firing rates in healthy and parkinsonian states.
Parkinsonism leads to various electrophysiological changes in the basal ganglia-thalamocortical system (BGTCS), often including elevated discharge rates of the subthalamic nucleus (STN) and the output nuclei, and reduced activity of the globus pallidus external (GPe) segment. These rate changes have been explained qualitatively in terms of the direct/indirect pathway model, involving projections of distinct striatal populations to the output nuclei and GPe. Although these populations partly overlap, evidence suggests dopamine depletion differentially affects cortico-striato-pallidal connection strengths to the two pallidal segments. Dopamine loss may also decrease the striatal signal-to-noise ratio, reducing both corticostriatal coupling and striatal firing thresholds. Additionally, nigrostriatal degeneration may cause secondary changes including weakened lateral inhibition in the GPe, and mesocortical dopamine loss may decrease intracortical excitation and especially inhibition. Here a mean-field model of the BGTCS is presented with structure and parameter estimates closely based on physiology and anatomy. Changes in model rates due to the possible effects of dopamine loss listed above are compared with experiment. Our results suggest that a stronger indirect pathway, possibly combined with a weakened direct pathway, is compatible with empirical evidence. However, altered corticostriatal connection strengths are probably not solely responsible for substantially increased STN activity often found. A lower STN firing threshold, weaker intracortical inhibition, and stronger striato-GPe inhibition help explain the relatively large increase in STN rate. Reduced GPe-GPe inhibition and a lower GPe firing threshold can account for the comparatively small decrease in GPe rate frequently observed. Changes in cortex, GPe, and STN help normalize the cortical rate, also in accord with experiments. The model integrates the basal ganglia into a unified framework along with an existing thalamocortical model that already accounts for a wide range of electrophysiological phenomena. A companion paper discusses the dynamics and oscillations of this combined system.
van Albada
S J
SJ
School of Physics, The University of Sydney, New South Wales 2006, Australia. albada@physics.usyd.edu.au
Robinson
P A
PA
D000328:Adult; D000818:Animals; D001479:Basal Ganglia / Q000502:physiology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D008959:Models, Neurological; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D020734:Parkinsonian Disorders / Q000503:physiopathology*; D020531:Subthalamic Nucleus / Q000502:physiology / Q000503:physiopathology; D013788:Thalamus / Q000502:physiology* / Q000503:physiopathology