title: Kv1.2 mediates heterosynaptic modulation of direct cortical synaptic inputs in CA3 pyramidal cells.
abstract: CONCLUSIONS
  We investigated the cellular mechanisms underlying mossy fibre-induced heterosynaptic long-term potentiation of perforant path (PP) inputs to CA3 pyramidal cells. Here we show that this heterosynaptic potentiation is mediated by downregulation of Kv1.2 channels. The downregulation of Kv1.2 preferentially enhanced PP-evoked EPSPs which occur at distal apical dendrites. Such enhancement of PP-EPSPs required activation of dendritic Na(+) channels, and its threshold was lowered by downregulation of Kv1.2. Our results may provide new insights into the long-standing question of how mossy fibre inputs constrain the CA3 network to sparsely represent direct cortical inputs.
  A short high frequency stimulation of mossy fibres (MFs) induces long-term potentiation (LTP) of direct cortical or perforant path (PP) synaptic inputs in hippocampal CA3 pyramidal cells (CA3-PCs). However, the cellular mechanism underlying this heterosynaptic modulation remains elusive. Previously, we reported that repetitive somatic firing at 10 Hz downregulates Kv1.2 in the CA3-PCs. Here, we show that MF inputs induce similar somatic firing and downregulation of Kv1.2 in the CA3-PCs. The effect of Kv1.2 downregulation was specific to PP synaptic inputs that arrive at distal apical dendrites. We found that the somatodendritic expression of Kv1.2 is polarized to distal apical dendrites. Compartmental simulations based on this finding suggested that passive normalization of synaptic inputs and polarized distributions of dendritic ionic channels may facilitate the activation of dendritic Na(+) channels preferentially at distal apical dendrites. Indeed, partial block of dendritic Na(+) channels using 10 nm tetrodotoxin brought back the enhanced PP-evoked excitatory postsynaptic potentials (PP-EPSPs) to the baseline level. These results indicate that activity-dependent downregulation of Kv1.2 in CA3-PCs mediates MF-induced heterosynaptic LTP of PP-EPSPs by facilitating activation of Na(+) channels at distal apical dendrites.
authors.affiliation: Cell Physiology Laboratory, Department of Physiology and bioMembrane Plasticity Research Centre, Seoul National University College of Medicine and Neuroscience Research Institute, Seoul National University Medical Research Centre, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Republic of Korea.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Hyun
authors.affiliation: Cell Physiology Laboratory, Department of Physiology and bioMembrane Plasticity Research Centre, Seoul National University College of Medicine and Neuroscience Research Institute, Seoul National University Medical Research Centre, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Republic of Korea.
authors.forename: Kisang
authors.initials: K
authors.lastname: Eom
authors.affiliation: Cell Physiology Laboratory, Department of Physiology and bioMembrane Plasticity Research Centre, Seoul National University College of Medicine and Neuroscience Research Institute, Seoul National University Medical Research Centre, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Republic of Korea.
authors.forename: Kyu-Hee
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Oral Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, 700-412, Republic of Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Bae
authors.affiliation: Department of Oral Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, 700-412, Republic of Korea.
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Bae
authors.affiliation: Cell Physiology Laboratory, Department of Physiology and bioMembrane Plasticity Research Centre, Seoul National University College of Medicine and Neuroscience Research Institute, Seoul National University Medical Research Centre, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Republic of Korea.
authors.forename: Myoung-Hwan
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Cell Physiology Laboratory, Department of Physiology and bioMembrane Plasticity Research Centre, Seoul National University College of Medicine and Neuroscience Research Institute, Seoul National University Medical Research Centre, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Republic of Korea.
authors.forename: Sooyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Cell Physiology Laboratory, Department of Physiology and bioMembrane Plasticity Research Centre, Seoul National University College of Medicine and Neuroscience Research Institute, Seoul National University Medical Research Centre, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Republic of Korea.
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Ho
authors.affiliation: Cell Physiology Laboratory, Department of Physiology and bioMembrane Plasticity Research Centre, Seoul National University College of Medicine and Neuroscience Research Institute, Seoul National University Medical Research Centre, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Republic of Korea.
authors.forename: Suk-Ho
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000502:physiology*; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D051663:Kv1.2 Potassium Channel / Q000235:genetics / Q000502:physiology*; D017774:Long-Term Potentiation; D008297:Male; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000502:physiology; D019580:Perforant Pathway; D017966:Pyramidal Cells / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission
chemical_list: D051663:Kv1.2 Potassium Channel