Kv4.2 knockout mice have hippocampal-dependent learning and memory deficits

  1. Anne E. Anderson1,2,4,5,7
  1. 1Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas 77030, USA
  2. 2Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA
  3. 3Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
  4. 4Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA
  5. 5Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA

    Abstract

    Kv4.2 channels contribute to the transient, outward K+ current (A-type current) in hippocampal dendrites, and modulation of this current substantially alters dendritic excitability. Using Kv4.2 knockout (KO) mice, we examined the role of Kv4.2 in hippocampal-dependent learning and memory. We found that Kv4.2 KO mice showed a deficit in the learning phase of the Morris water maze (MWM) and significant impairment in the probe trial compared with wild type (WT). Kv4.2 KO mice also demonstrated a specific deficit in contextual learning in the fear-conditioning test, without impairment in the conditioned stimulus or new context condition. Kv4.2 KO mice had normal activity, anxiety levels, and prepulse inhibition compared with WT mice. A compensatory increase in tonic inhibition has been previously described in hippocampal slice recordings from Kv4.2 KO mice. In an attempt to decipher whether increased tonic inhibition contributed to the learning and memory deficits in Kv4.2 KO mice, we administered picrotoxin to block GABAA receptors (GABAAR), and thereby tonic inhibition. This manipulation had no effect on behavior in the WT or KO mice. Furthermore, total protein levels of the α5 or δ GABAAR subunits, which contribute to tonic inhibition, were unchanged in hippocampus. Overall, our findings add to the growing body of evidence, suggesting an important role for Kv4.2 channels in hippocampal-dependent learning and memory.

    Footnotes

    • 6 Present address: Baylor University, Department of Psychology and Neuroscience, Waco, TX 76706, USA.

    • 7 Corresponding author.

      E-mail annea{at}bcm.edu.

    • Received July 19, 2011.
    • Accepted February 22, 2012.
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