Frequency-selectivity of a thalamocortical relay neuron during Parkinson's disease and deep brain stimulation: a computational study.
In this computational study, we investigated (i) the functional importance of correlated basal ganglia (BG) activity associated with Parkinson's disease (PD) motor symptoms by analysing the effects of globus pallidus internum (GPi) bursting frequency and synchrony on a thalamocortical (TC) relay neuron, which received GABAergic projections from this nucleus; (ii) the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on the response of the TC relay neuron to synchronized GPi oscillations; and (iii) the functional basis of the inverse relationship that has been reported between DBS frequency and stimulus amplitude, required to alleviate PD motor symptoms [A. L. Benabid et al. (1991)Lancet, 337, 403-406]. The TC relay neuron selectively responded to and relayed synchronized GPi inputs bursting at a frequency located in the range 2-25 Hz. Input selectivity of the TC relay neuron is dictated by low-threshold calcium current dynamics and passive membrane properties of the neuron. STN-DBS prevented the TC relay neuron from relaying synchronized GPi oscillations to cortex. Our model indicates that DBS alters BG output and input selectivity of the TC relay neuron, providing an explanation for the clinically observed inverse relationship between DBS frequency and stimulus amplitude.
Philips Research Laboratories, High Tech Campus, Eindhoven, Netherlands. hayriye.cagnan@philips.com
Hayriye
H
Cagnan
Hil G E
HG
Meijer
Stephan A
SA
van Gils
Martin
M
Krupa
Tjitske
T
Heida
Michelle
M
Rudolph
Wytse J
WJ
Wadman
Hubert C F
HC
Martens
D000465:Algorithms; D001921:Brain / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000503:physiopathology; D003198:Computer Simulation; D046690:Deep Brain Stimulation / Q000379:methods*; D003712:Dendrites / Q000502:physiology; D020820:Dyskinesias / Q000503:physiopathology / Q000628:therapy; D005917:Globus Pallidus / Q000503:physiopathology; D006801:Humans; D008564:Membrane Potentials; D008959:Models, Neurological; D009434:Neural Pathways / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D010300:Parkinson Disease / Q000503:physiopathology* / Q000628:therapy*; D010507:Periodicity; D020531:Subthalamic Nucleus / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005680:gamma-Aminobutyric Acid; D002118:Calcium