Abstract
Histamine-containing neurons of the tuberomammilary nucleus project to the hippocampal formation to innervate H1 and H2 receptors on both principal and inhibitory interneurons. Here we show that H2 receptor activation negatively modulates outward currents through Kv3.2-containing potassium channels by a mechanism involving PKA phosphorylation in inhibitory interneurons. PKA phosphorylation of Kv3.2 lowered the maximum firing frequency of inhibitory neurons, which in turn negatively modulated high-frequency population oscillations recorded in principal cell layers. All these effects were absent in a Kv3.2 knockout mouse. These data reveal a novel pathway for histamine-dependent regulation of high-frequency oscillations within the hippocampal formation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-Methyl-3-isobutylxanthine / pharmacology
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Animals
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Bucladesine / pharmacology
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Cyclic AMP / physiology
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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Dimaprit / pharmacology
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Hippocampus / physiology*
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In Vitro Techniques
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Interneurons / drug effects
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Interneurons / physiology*
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Mice
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Mice, Inbred C57BL
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Neuropeptides / metabolism
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Neuropeptides / physiology*
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Patch-Clamp Techniques
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Phosphorylation
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Picrotoxin / pharmacology
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Potassium Channels / metabolism
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Potassium Channels / physiology*
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Potassium Channels, Voltage-Gated*
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Pyramidal Cells / drug effects
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Pyramidal Cells / physiology*
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Receptors, Histamine H2 / physiology*
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Shaw Potassium Channels
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Tetraethylammonium / pharmacology
Substances
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Neuropeptides
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Potassium Channels
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Potassium Channels, Voltage-Gated
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Receptors, Histamine H2
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Shaw Potassium Channels
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Picrotoxin
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Bucladesine
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Tetraethylammonium
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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1-Methyl-3-isobutylxanthine
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Dimaprit