A Behavioral Role for Dendritic IntegrationHCN1 Channels Constrain Spatial Memory and Plasticity at Inputs to Distal Dendrites of CA1 Pyramidal Neurons

Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.
Cell (Impact Factor: 32.24). 12/2004; 119(5):719-32. DOI: 10.1016/j.cell.2004.11.020
Source: PubMed


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.

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    • "We flanked exon II of the CPEB3 gene and the neomycin selection marker with two loxP sites by homologous recombination in embryonic stem (ES) cells (Figure 2A). To generate conditional lines that have both spatial and temporal patterns of CPEB3 recombination, we crossed the CPEB3 floxed mice to CaMKII-Cre transgenic mice (Nolan et al., 2004). In situ hybridization revealed an almost complete ablation of CPEB3 mRNA expression in the hippocampus and cortex in the CPEB3 CKO mice, compared with wild-type (WT) control mice (Figure 2B). "
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    • "Hyperpolarization-activated cation current (Ih) is conducted by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and has been described in multiple neuronal types, such as thalamic neurons, hippocampal CA1 pyramidal neurons, primary afferent neurons, and spinal dorsal horn neurons (Doan et al., 2004; Gao et al., 2012; Ingram and Williams, 1996; McCormick and Pape, 1990; Nolan et al., 2004; Rivera-Arconada et al., 2013). It is a mixed inward cationic current carried by Na + and K + . "
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