title: Hyperpolarization-activated, cyclic nucleotide-gated cation channels in Aplysia: Contribution to classical conditioning.
abstract: Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are critical regulators of neuronal excitability, but less is known about their possible roles in synaptic plasticity and memory circuits. Here, we characterized the HCN gene organization, channel properties, distribution, and involvement in associative and nonassociative forms of learning in Aplysia californica. Aplysia has only one HCN gene, which codes for a channel that has many similarities to the mammalian HCN channel. The cloned acHCN gene was expressed in Xenopus oocytes, which displayed a hyperpolarization-induced inward current that was enhanced by cGMP as well as cAMP. Similarly to its homologs in other animals, acHCN is permeable to K(+) and Na(+) ions, and is selectively blocked by Cs(+) and ZD7288. We found that acHCN is predominantly expressed in inter- and motor neurons, including LFS siphon motor neurons, and therefore tested whether HCN channels are involved in simple forms of learning of the siphon-withdrawal reflex in a semiintact preparation. ZD7288 (100 μM) significantly reduced an associative form of learning (classical conditioning) but had no effect on two nonassociative forms of learning (intermediate-term sensitization and unpaired training) or baseline responses. The HCN current is enhanced by nitric oxide (NO), which may explain the postsynaptic role of NO during conditioning. HCN current in turn enhances the NMDA-like current in the motor neurons, suggesting that HCN channels contribute to conditioning through this pathway.
authors.affiliation: Department of Neuroscience, Columbia University, New York, NY 10032;
authors.forename: Qizong
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Whitney Laboratory for Marine Biosciences, University of Florida, St. Augustine, FL 32080;
authors.forename: Pavlo
authors.initials: P
authors.lastname: Kuzyk
authors.affiliation: Department of Neuroscience, Columbia University, New York, NY 10032;
authors.forename: Igor
authors.initials: I
authors.lastname: Antonov
authors.affiliation: Whitney Laboratory for Marine Biosciences, University of Florida, St. Augustine, FL 32080; Department of Neuroscience, University of Florida, Gainesville, FL 32610;
authors.forename: Caleb J
authors.initials: CJ
authors.lastname: Bostwick
authors.affiliation: Whitney Laboratory for Marine Biosciences, University of Florida, St. Augustine, FL 32080;
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Kohn
authors.affiliation: Whitney Laboratory for Marine Biosciences, University of Florida, St. Augustine, FL 32080; Department of Neuroscience, University of Florida, Gainesville, FL 32610; rdh1@columbia.edu moroz@whitney.ufl.edu.
authors.forename: Leonid L
authors.initials: LL
authors.lastname: Moroz
authors.affiliation: Department of Neuroscience, Columbia University, New York, NY 10032; Division of Neurobiology and Behavior, New York State Psychiatric Institute, New York, NY 10032 rdh1@columbia.edu moroz@whitney.ufl.edu.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Hawkins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000502:physiology*; D005260:Female; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D011743:Pyrimidines; C082246:ICI D2788; D009569:Nitric Oxide; D012964:Sodium; D000242:Cyclic AMP; D006152:Cyclic GMP; D011188:Potassium
keywords: Aplysia; HCN channels; NMDA; learning and memory; nitric oxide