title: A behavioral role for dendritic integration: HCN1 channels constrain spatial memory and plasticity at inputs to distal dendrites of CA1 pyramidal neurons.
abstract: The importance of long-term synaptic plasticity as a cellular substrate for learning and memory is well established. By contrast, little is known about how learning and memory are regulated by voltage-gated ion channels that integrate synaptic information. We investigated this question using mice with general or forebrain-restricted knockout of the HCN1 gene, which we find encodes a major component of the hyperpolarization-activated inward current (Ih) and is an important determinant of dendritic integration in hippocampal CA1 pyramidal cells. Deletion of HCN1 from forebrain neurons enhances hippocampal-dependent learning and memory, augments the power of theta oscillations, and enhances long-term potentiation (LTP) at the direct perforant path input to the distal dendrites of CA1 pyramidal neurons, but has little effect on LTP at the more proximal Schaffer collateral inputs. We suggest that HCN1 channels constrain learning and memory by regulating dendritic integration of distal synaptic inputs to pyramidal cells.
authors.affiliation: Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Nolan
authors.forename: Gaël
authors.initials: G
authors.lastname: Malleret
authors.forename: Josh T
authors.initials: JT
authors.lastname: Dudman
authors.forename: Derek L
authors.initials: DL
authors.lastname: Buhl
authors.forename: Bina
authors.initials: B
authors.lastname: Santoro
authors.forename: Emma
authors.initials: E
authors.lastname: Gibbs
authors.forename: Svetlana
authors.initials: S
authors.lastname: Vronskaya
authors.forename: György
authors.initials: G
authors.lastname: Buzsáki
authors.forename: Steven A
authors.initials: SA
authors.lastname: Siegelbaum
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
authors.forename: Alexei
authors.initials: A
authors.lastname: Morozov
mesh_terms: D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D019580:Perforant Pathway / Q000378:metabolism; D015221:Potassium Channels; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology*; D013028:Space Perception / Q000502:physiology; D013569:Synapses / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics*; D013826:Theta Rhythm
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C578666:Hcn1 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D015221:Potassium Channels