Abstract
Hippocampal long-term potentiation (LTP) induced by theta-burst pairing of Schaffer collateral inputs and postsynaptic firing is associated with localized increases in synaptic strength and dendritic excitability. Using the same protocol, we now demonstrate a decrease in cellular excitability that was blocked by the h-channel blocker ZD7288. This decrease was also induced by postsynaptic theta-burst firing alone, yet it was blocked by NMDA receptor antagonists, postsynaptic Ca2+ chelation, low concentrations of tetrodotoxin, omega-conotoxin MVIIC, calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors and a protein synthesis inhibitor. Increasing network activity with high extracellular K+ caused a similar reduction of cellular excitability and an increase in h-channel HCN1 protein. We propose that backpropagating action potentials open glutamate-bound NMDA receptors, resulting in an increase in I(h) and a decrease in overall excitability. The occurrence of such a reduction in cellular excitability in parallel with synaptic potentiation would be a negative feedback mechanism to normalize neuronal output firing and thus promote network stability.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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Animals
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Animals, Newborn
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Blotting, Western / methods
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Calcium / metabolism
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Calcium Channel Blockers / pharmacology
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Cardiovascular Agents / pharmacology
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Cyclic Nucleotide-Gated Cation Channels
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Diagnostic Imaging / methods
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Dizocilpine Maleate / pharmacology
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Dose-Response Relationship, Drug
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Drug Interactions
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Hippocampus / cytology*
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Hippocampus / physiology
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Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
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In Vitro Techniques
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Ion Channels / antagonists & inhibitors
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Ion Channels / physiology*
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology
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Long-Term Potentiation / radiation effects
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Male
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Membrane Potentials / drug effects
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Membrane Potentials / physiology*
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Membrane Potentials / radiation effects
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Neurons / physiology*
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Organophosphates / pharmacology
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Patch-Clamp Techniques / methods
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Potassium Channels
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Potassium Chloride / pharmacology
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Pyrimidines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Sodium Channel Blockers / pharmacology
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Statistics, Nonparametric
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Tetrodotoxin / pharmacology
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Time Factors
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omega-Conotoxins / pharmacology
Substances
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Calcium Channel Blockers
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Cardiovascular Agents
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Cyclic Nucleotide-Gated Cation Channels
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Enzyme Inhibitors
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Excitatory Amino Acid Antagonists
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Hcn1 protein, rat
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Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
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Ion Channels
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Organophosphates
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Potassium Channels
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Pyrimidines
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Sodium Channel Blockers
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omega-Conotoxins
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ICI D2788
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omega-conotoxin-MVIIC
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Tetrodotoxin
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Potassium Chloride
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Dizocilpine Maleate
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2-Amino-5-phosphonovalerate
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tributyl phosphate
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Calcium