title: Activity-dependent decrease of excitability in rat hippocampal neurons through increases in I(h).
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.
authors.affiliation: Center for Learning and Memory, University of Texas at Austin, 1 University Station, C7000, Austin, Texas 78712, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fan
authors.forename: Desdemona
authors.initials: D
authors.lastname: Fricker
authors.forename: Darrin H
authors.initials: DH
authors.lastname: Brager
authors.forename: Xixi
authors.initials: X
authors.lastname: Chen
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Lu
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Chitwood
authors.forename: Daniel
authors.initials: D
authors.lastname: Johnston
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D003952:Diagnostic Imaging / Q000379:methods; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000502:physiology*; D010755:Organophosphates / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels; D011189:Potassium Chloride / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D002317:Cardiovascular Agents; D054815:Cyclic Nucleotide-Gated Cation Channels; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; C578667:Hcn1 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D010755:Organophosphates; D015221:Potassium Channels; D011743:Pyrimidines; D026941:Sodium Channel Blockers; D020960:omega-Conotoxins; C082246:ICI D2788; C075851:omega-conotoxin-MVIIC; D013779:Tetrodotoxin; D011189:Potassium Chloride; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; C009524:tributyl phosphate; D002118:Calcium