A behavioral role for dendritic integration: HCN1 channels constrain spatial memory and plasticity at inputs to distal dendrites of CA1 pyramidal neurons.
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.
Nolan
Matthew F
MF
Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.
Malleret
Gaël
G
Dudman
Josh T
JT
Buhl
Derek L
DL
Santoro
Bina
B
Gibbs
Emma
E
Vronskaya
Svetlana
S
Buzsáki
György
G
Siegelbaum
Steven A
SA
Kandel
Eric R
ER
Morozov
Alexei
A
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
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