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J Neurophysiol (September 7, 2005). doi:10.1152/jn.00525.2005
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Submitted on May 20, 2005
Accepted on September 1, 2005

Membrane channel interactions underlying rat subthalamic projection neuron rhythmic and bursting activity

Andrew Gillies* and David Willshaw

* To whom correspondence should be addressed. E-mail: andrew{at}anc.ed.ac.uk.

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 behaviours characteristic of rat subthalamic neurons. It reveals that a key set of three channels play a primary role in distinguishing behaviours: a high voltage activated calcium channel (Cav1.2-1.3), a low voltage activated calcium channel (Cav3.-), and a small current calcium activated potassium channel (KCa2.1-2.3). Short and long post-hyperpolarisation rebound responses, low frequency rhythmic bursting (<1Hz), higher frequency rhythmic bursting (4-7Hz) and slow action and depolarising potentials are behaviours all mediated by the interaction of these channels. This interaction can generate a robust calcium-dependent extended depolarisation in the dendrites (a depolarising 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 depolarising plateau. A number of important predictions arise from the model. For example, blocking or disrupting the low voltage activated Cav3.- calcium current should mute the emergence of rebound responses and rhythmic bursting. Conversely, increasing this channel current via large hyperpolarising 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.




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