Regulatory Mechanisms And Synaptic Pharmacology Of Serotonergic Neurons In The Dorsal Raphe Nucleus, Median Raphe Nucleus And Raphe Pallidus Nucleus In Mouse Brain Slices In Vitro.

Studies were designed to investigate the regulatory mechanism involved in maintaining the spontaneous activity of serotonergic neurons in the DRN, MRN and RPN. In vitro recordings were made within these nuclei in order to determine the effects of several different compounds on firing rates and cell/track ratios. Neurons within the DRN, MRN and RPN displayed rhythmic discharge rates. Pretreatment with PCPA or treatment with high magnesium, low calcium produced no significant change in the firing rates of these neurons. Apparently, stringent levels of intracellular serotonin are not necessary for maintaining the spontaneous activity of serotonergic neurons. Phenylephrine administration produced no change in discharge rates of DRN neurons in slices obtained from unanesthetized mice. However, phenylephrine dramatically increased the discharge rates and cell/track ratios of neurons in slices obtained from mice which were first anesthetized with halothane. These findings suggest that the spontaneous activity of serotonergic neurons is not dependent upon an excitatory noradrenergic input, but noradrenergic inputs apparently modulate the activity of serotonergic neurons under abnormal conditions. Elevations of calcium levels in the incubation medium decreased the discharge rates and cell/track ratio of DRN neurons. High intracellular calcium may decrease the discharge rates of serotonergic neurons by increasing the afterhyperpolarization which follows each action potential. Neurochemical data suggest that serotonin is synthesized at higher rates in the high calcium condition. Most of the excess neurotransmitter seems to be stored intracellular, since no 5-HIAA was detectable in the high calcium medium. These results are discussed in terms of their involvement in affective disorders such as depression. Another set of experiments was designed to investigate the role of autoreceptors in the regulation of serotonergic neuronal activity. Autoreceptors appear to function by inhibiting serotonergic neuronal activity in the presence of excess serotonin in the slice