Simplified models of pacemaker spiking in raphe and locus coeruleus neurons

Abstract

Many central neurons, and in particular certain brainstem aminergic neurons exhibit spontaneous and fairly regular spiking with frequencies of order a few Hz. A large number of ion channel types contribute to such spiking so that accurate modeling of spike generation leads to the requirement of solving very large systems of differential equations, ordinary in the first instance. Since analysis of spiking behavior when many synaptic inputs are active adds further to the number of components, it is useful to have simplified mathematical models of spiking in such neurons so that, for example, stochastic features of inputs and output spike trains can be incorporated. In this article we investigate two simple two-component models which mimic features of spiking in serotonergic neurons of the dorsal raphe nucleus and noradrenergic neurons of the locus coeruleus. The first model is of the Fitzhugh-Nagumo type and the second is a reduced Hodgkin-Huxley model. For each model solutions are computed with two representative sets of parameters. Frequency versus input currents are found and reveal Hodgkin type 2 behavior. For the first model a bifurcation and phase plane analysis supports these findings. The spike trajectories in the second model are very similar to those in DRN SE pacemaker activity but there are more parameters than in the Fitzhugh-Nagumo type model. The article concludes with a brief review of previous modeling of these types of neurons and its relevance to studies of serotonergic involvement in spatial working memory and obsessive-compulsive disorder.