Abstract
The hippocampus receives a dense serotonin-containing innervation from the divisions of the raphe nucleus1,2. Serotonin applied to hippocampal neurons to mimic the action of endogenous transmitter often produces complex and variable responses (see for example ref. 3). Using voltage-clamp methods and new ligands that are selective for subtypes of serotonin receptors4,5, we have been able to clarify the mechanism of serotonin action on CA1 cells in rat hippocampal slices. We describe three distinct actions of serotonin (or 5-HT) on identified K-conductances in these cells. First, it activates a Ca-independent K-current which is responsible for neuronal hyperpolarization and is inhibitory. Second, it simultaneously suppresses the slow Ca-dependent K-conductance that is largely responsible for the accommodation of cell firing in CA1 neurons6–8: this produces a paradoxical increase in neuronal dis-charge in response to a depolarizing input. Third, serotonin produces a more slowly developing and long-lasting suppression of an intrinsic voltage-dependent K-conductance, Im (ref. 9), leading to neuronal depolarization and excitation. The hyperpolarizing response is mediated by class 1A serotonin receptors, whereas the other responses are not. Modulation of these different conductances by endogenously released serotonin could therefore change the probability or the duration (or both) of neuronal firing in the mammalian brain in different ways to give inhibitory, excitatory or mixed effects.
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Colino, A., Halliwell, J. Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin. Nature 328, 73–77 (1987). https://doi.org/10.1038/328073a0
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DOI: https://doi.org/10.1038/328073a0
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