Membrane channel interactions underlying rat subthalamic projection neuron rhythmic and bursting activity.
A computational model of the rat subthalamic nucleus projection neuron is constructed using electrophysiological and morphological data and a restricted set of channel specifications. The model cell exhibits a wide range of electrophysiological behaviors characteristic of rat subthalamic neurons. It reveals that a key set of three channels play a primary role in distinguishing behaviors: a high-voltage-activated calcium channel (Cav 1.2.-1.3), a low-voltage-activated calcium channel (Cav 3.-), and a small current calcium-activated potassium channel (KCa 2.1-2.3). Short and long posthyperpolarization rebound responses, low-frequency rhythmic bursting (< 1 Hz), higher-frequency rhythmic bursting (4-7 Hz), and slow action and depolarizing potentials are behaviors all mediated by the interaction of these channels. This interaction can generate a robust calcium-dependent extended depolarization in the dendrites (a depolarizing plateau). The diversity observed in the rat subthalamic physiology (such as short or long rebounds, or the presence of low-frequency rhythmic busting) can arise from alterations in both the density and distributions of these channel types and, consequently, their ability to generate this depolarizing plateau. A number of important predictions arise from the model. For example, blocking or disrupting the low-voltage-activated Cav 3.- calcium current should mute the emergence of rebound responses and rhythmic bursting. Conversely, increasing this channel current via large hyperpolarizing potentials in combination with partial blockade of the high-voltage-activated calcium channels should lead to the more experimentally elusive in vitro high-frequency bursting.
Gillies
Andrew
A
Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh, United Kingdom. andrew@anc.ed.ac.uk
Willshaw
David
D
D000200:Action Potentials; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D004594:Electrophysiology; D007473:Ion Channels / Q000502:physiology*; D008433:Mathematics; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D051381:Rats; D020531:Subthalamic Nucleus / Q000502:physiology*; D013997:Time Factors
D015220:Calcium Channels; D007473:Ion Channels; D024681:Potassium Channels, Calcium-Activated