title: Increased neuronal excitability, synaptic plasticity, and learning in aged Kvbeta1.1 knockout mice.
abstract: BACKGROUND
  Advancing age is typically accompanied by deficits in learning and memory. These deficits occur independently of overt pathology and are often considered to be a part of "normal aging." At the neuronal level, normal aging is known to be associated with numerous cellular and molecular changes, which include a pronounced decrease in neuronal excitability and an altered induction in the threshold for synaptic plasticity. Because both of these mechanisms (neuronal excitability and synaptic plasticity) have been implicated as putative cellular substrates for learning and memory, it is reasonable to propose that age-related changes in these mechanisms may contribute to the general cognitive decline that occurs during aging.
  
  
  RESULTS
  To further investigate the relationship between aging, learning and memory, neuronal excitability, and synaptic plasticity, we have carried out experiments with aged mice that lack the auxiliary potassium channel subunit Kvbeta1.1. In aged mice, the deletion of the auxiliary potassium channel subunit Kvbeta1.1 resulted in increased neuronal excitability, as measured by a decrease in the post-burst afterhyperpolarization. In addition, long-term potentiation (LTP) was more readily induced in aged Kvbeta1.1 knockout mice. Finally, the aged Kvbeta1.1 mutants outperformed age-matched controls in the hidden-platform version of the Morris water maze. Interestingly, the enhancements in excitability and learning were both sensitive to genetic background: The enhanced learning was only observed in a genetic background in which the mutants exhibited increased neuronal excitability.
  
  
  CONCLUSIONS
  Neuronal excitability is an important determinant of both synaptic plasticity and learning in aged subjects.
authors.affiliation: Departments of Neurobiology, Psychology, and Psychiatry, Brain Research Institute, University of California, Los Angeles, 2554 Gonda Center, Box 951761, Los Angeles, CA 90095, USA.
authors.forename: Geoffrey G
authors.initials: GG
authors.lastname: Murphy
authors.forename: Nikolai B
authors.initials: NB
authors.lastname: Fedorov
authors.forename: K Peter
authors.initials: KP
authors.lastname: Giese
authors.forename: Masuo
authors.initials: M
authors.lastname: Ohno
authors.forename: Eugenia
authors.initials: E
authors.lastname: Friedman
authors.forename: Rachel
authors.initials: R
authors.lastname: Chen
authors.forename: Alcino J
authors.initials: AJ
authors.lastname: Silva
mesh_terms: D000200:Action Potentials; D000375:Aging / Q000502:physiology*; D000818:Animals; D004594:Electrophysiology; D051662:Kv1.1 Potassium Channel; D051664:Kv1.3 Potassium Channel; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D007858:Learning / Q000502:physiology*; D018782:Maze Learning; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated / Q000172:deficiency*; D013569:Synapses / Q000502:physiology*
chemical_list: C496947:Kcna1 protein, mouse; C494838:Kcnab1 protein, mouse; D051664:Kv1.3 Potassium Channel; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel