Sodium dynamics underlying burst firing and putative mechanisms for the regulation of the firing pattern in midbrain dopamine neurons: a computational approach.
A physiologically based multicompartmental computational model of a midbrain dopamine (DA) neuron, calibrated using data from the literature, was developed and used to test the hypothesis that sodium dynamics drive the generation of a slow oscillation postulated to underlie NMDA-evoked bursting activity in a slice preparation. The full compartmental model was reduced to three compartments and ultimately to two variables, while retaining the biophysical interpretation of all parameters. A phase-plane analysis then suggested two mechanisms for the regulation of the firing pattern: (1) bursting activity is favored by manipulations that enhance the region of negative slope in the whole-cell IV curve and inhibited by those manipulations, such as increasing linear currents, that tend to dampen this region and (2) assuming a region of negative slope is present in the IV curve, the bias of the system can be altered, either enabling or disabling bursting. The model provides a coherent framework for interpreting the effects of glutamate, aspartate, NMDA, and GABA agonists and antagonists under current-clamp conditions, as well as the effects of NMDA and barium under voltage-clamp conditions.
Canavier
C C
CC
Department of Psychology, University of New Orleans, LA 70148, USA. ccanavie@uno.edu
D002138:Calibration; D003198:Computer Simulation; D004298:Dopamine / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009991:Oscillometry; D018408:Patch-Clamp Techniques; D012964:Sodium / Q000378:metabolism*
D016202:N-Methylaspartate; D012964:Sodium; D004298:Dopamine