Brainstem and lower nuclei contain neurons which are the principal CNS sources of the neurotransmitters serotonin (dorsal and other raphe nuclei) and noradrenaline (locus coeruleus and associated centers). By means of vast ascending and descending tracts with extensive arborizations, these transmitters influence the physiological activity of practically every neuron (and some glia) in the CNS, including the cerebral cortex, hippocampus, cerebellum, spinal cord and the brainstem itself. The noradrenergic and serotonergic systems are intertwined, with reciprocal connections and common afferents so that their properties cannot really be studied independently of each other. Noradrenaline and serotonin are implicated in sleep and many affective and cognitive disorders, as indicated by genetic studies and the therapeutic efficacy of drugs which inhibit their transporters. The neuronal and endocrine circuits involving their actions are numerous and complex. Serotonergic neurons of the DRN, for example, are host to about 17 receptor types (Maejima et al., 2013, Frontiers Int. Neurosci. 7, #40) and there are about 15 neurotransmitters which are known to inhibit noradrenaline release (Kubista & Boehm, 2006, Pharmacology & Therapeutics 112, 213-242). Several groups, including researchers at OSU, have commenced quantitative research on these systems. We will examine some of these studies, including recently published mathematical modeling of spike generation in serotonergic neurons (HCT and NJ Penington, Progress in Neurobiology, 2014) and analysis of the interactions between the noradrenergic and serotonergic systems. Joint research with BP Guiard (Toulouse) and NJ Penington (New York).