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Serotonergic neurons of the dorsal raphe nucleus, with their extensive innervation of limbic and higher brain regions and intreractions with the endocrine system have important modulatory or regulatory effects on many cognitive, emotional and physiological processes. They have been strongly implicated in responses to stress and in the occurrence of major depressive disorder and other pyschiatric disorders. In order to quantify some of these effects, detailed mathematical models of the activity of such cells are required which describe their complex neurochemistry and neurophysiology.
As a first step, we consider here a single-compartment model of these neurons which is capable of describing many of the known features of spike generation, particularly the slow rhythmic pacemaking activity often observed in these cells in a variety of species. Included in the model are ten kinds of voltage dependent ion channnels as well as calcium-dependent potassium current. Calcium dynamics includes buffering and pumping. In sections 3-9, each component is considered in detail and parameters estimated from voltage clamp data where possible. In the next two sections simplified versions of some components are employed to explore the effects of various parameters on spiking, using a systematic approach, ending up with the following eleven components: a fast sodium current
Attention is focused on the properties usually associated with these neurons, particularly long duration of action potential, pacemaker-like spiking and the ramp-like return to threshold after a spike. In some cases the membrane potential trajectories display doublets or have kinks or notches as have been reported in some experimental studies. The computed time courses of