What drives midbrain dopaminergic neurons to oscillate at high frequencies?

Alexey Kuznetsov
Department of Mathematical Sciences, Indiana University--Purdue University

(April 6, 2007 3:30 PM - 4:30 PM)

What drives midbrain dopaminergic neurons to oscillate at high frequencies?

Abstract

Mesencephalic dopamine neurons ordinarily will not fire faster than about 10/s in response to somatic current injections. However, in response to dendritic excitation, much higher rates are briefly attained. In analysis of a simplified biophysical model, we have suggested a way such transient high-frequency firing may be evoked. The neuron is represented as a number of electrically coupled compartments with different natural frequencies, which correspond to the soma and parts of the dendrite. The model is highly reduced: all the diversity of the compartments that describes real dendritic geometry is substituted by a pair of compartments: the slowest, somatic and the fastest, the most distal dendritic one. In the absence of any synaptic stimulation, oscillatory pattern in this model is controlled by the somatic compartment, and, therefore, has a very low frequency. We consider and compare the influence of N-methyl-D-aspartate (NMDA) and alpha-amino-5-hydroxy-3-methyl-4-isoxazole propionic acid (AMPA) receptor activation in the dendritic compartment. The main result is that activation of the dendritic NMDA receptors evokes oscillations at a much higher frequency. Dendritic AMPA activation, by contrast, cannot increase the frequency significantly. We show that the elevated frequency emerges due to the domination by the dendritic compartment during the application of NMDA. We consider further details of the mechanisms of such domination in the present model as well as in a model comprised of a higher number of compartments.