Neurons in the central nervous system (CNS) often store more than one neurotransmitter, but as yet the functional significance of this type of coexistence is poorly understood. 5-Hydroxytryptamine (5-HT) modulates calcium-dependent K+ channels (KCa) responsible for the postspike afterhyperpolarization in different regions of the CNS. In lamprey, 5-HT neurons control apamine-sensitive KCa channels in spinal locomotor network interneurons, thereby in addition regulating the duration of locomotor bursts. We report here that these spinal 5-HT neurons also contain dopamine. Like 5-HT, dopamine causes a reduction of the afterhyperpolarization, but in this case it is due to a reduction of calcium entry during the action potential, which results in a reduced activation of KCa. 5-HT and dopamine are both released from these midline neurons, and both reduce the afterhyperpolarization through two distinctly different, but complementary cellular mechanisms. The net effect of dopamine (10-100 microM) on the locomotor network is similar to that of 5-HT, and the effects of dopamine and 5-HT are additive at the network level.

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In the lamprey spinal cord, dopamine- (DA) and 5-hydroxytryptamine-(5-HT) containing cells appear to play an important role in controlling the firing properties of motoneurons and interneurons and, thereby, in modulating the efferent motor pattern. To determine the detailed morphology and synaptic connectivity of the intraspinal DA and 5-HT systems in Lampetra fluviatilis and Ichthyomyzon unicuspis, DA and 5-HT antisera were used in light and electron microscopic immunocytochemical experiments. Two main groups of labeled cells were distinguished: DA-containing liquor-contacting (LC) cells distributed along the central canal, and 5-HT+DA-containing multipolar cells located near the midline ventral to the central canal. Both types were synaptically connected with other neuronal elements. The DA-immunoreactive LC cells, which extended a ciliated process into the central canal, received symmetrical synapses from unlabeled terminals containing small synaptic vesicles. The distal process of the LC cells could be traced to the lateral cell column, to the ventral aspect of the dorsal column, or to the ventromedial area. Ultrastructural analysis of DA fibers in these regions showed the presence of labeled terminals containing numerous small synaptic vesicles and a few dense-core vesicles. These terminals formed symmetrical synapses with unlabeled cell bodies and dendrites, with GABA-immunopositive LC cells, and with the multipolar DA+5-HT cells. The multipolar DA+5-HT cells also received input from unlabeled synapses. Intracellular recording from these cells showed that they received excitatory postsynaptic potentials in response to stimulation of fibers in the ventromedial tracts and dorsal roots. The terminals of the multipolar DA+5-HT neurons in the ventromedial spinal cord contained numerous dense-core vesicles and small synaptic vesicles, but no synaptic specializations could be detected. In addition, a small number of larger DA-immunoreactive cells were observed in the lateral cell column at rostral levels. The lamprey spinal cord thus contains distinct populations of synaptically interconnected monoaminergic neurons. Dopamine-containing LC cells synapse onto DA+5-HT-containing multipolar cells, in addition to GABAergic LC cells and unidentified spinal neurons. In contrast, the multipolar cells appear to exert their influence by nonsynaptic mechanisms.