title: Phase response curve analysis of a full morphological globus pallidus neuron model reveals distinct perisomatic and dendritic modes of synaptic integration.
abstract: Synchronization of globus pallidus (GP) neurons and cortically entrained oscillations between GP and other basal ganglia nuclei are key features of the pathophysiology of Parkinson's disease. Phase response curves (PRCs), which tabulate the effects of phasic inputs within a neuron's spike cycle on output spike timing, are efficient tools for predicting the emergence of synchronization in neuronal networks and entrainment to periodic input. In this study we apply physiologically realistic synaptic conductance inputs to a full morphological GP neuron model to determine the phase response properties of the soma and different regions of the dendritic tree. We find that perisomatic excitatory inputs delivered throughout the interspike interval advance the phase of the spontaneous spike cycle yielding a type I PRC. In contrast, we demonstrate that distal dendritic excitatory inputs can either delay or advance the next spike depending on whether they occur early or late in the spike cycle. We find this latter pattern of responses, summarized by a biphasic (type II) PRC, was a consequence of dendritic activation of the small conductance calcium-activated potassium current, SK. We also evaluate the spike-frequency dependence of somatic and dendritic PRC shapes, and we demonstrate the robustness of our results to variations of conductance densities, distributions, and kinetic parameters. We conclude that the distal dendrite of GP neurons embodies a distinct dynamical subsystem that could promote synchronization of pallidal networks to excitatory inputs. These results highlight the need to consider different effects of perisomatic and dendritic inputs in the control of network behavior.
authors.affiliation: Department of Biology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Schultheiss
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Edgerton
authors.forename: Dieter
authors.initials: D
authors.lastname: Jaeger
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D055592:Biophysical Phenomena / Q000502:physiology; D001703:Biophysics / Q000379:methods; D003198:Computer Simulation; D003712:Dendrites / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D005917:Globus Pallidus / Q000166:cytology*; D008959:Models, Neurological; D009431:Neural Conduction / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000166:cytology*; D018408:Patch-Clamp Techniques; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D051640:Small-Conductance Calcium-Activated Potassium Channels; D005680:gamma-Aminobutyric Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid