Spatial learning deficits in mice lacking A-type K ⁺ channel subunits

Kv4.2-mediated A-type K ⁺ channels in dendrites act to dampen back-propagating action potentials, constrain coincidence detection, and modify synaptic properties. Because of naturally high concentrations in the hippocampus, genetic deletion of this protein results in enhanced CA1 dendritic excitability and a broader signal integration time window with potential implications for spatial learning. In this investigation, we tested Kv4.2 knockout mice in the Morris water maze to assess their spatial reference acquisition and recall abilities. These mice demonstrated prolonged latencies and pathlength to reach a hidden platform during learning trials that was correlated to a decreased use of spatial search strategies in favor of repetitive looping. Knockout mice also showed no preference for target areas in recall-based probe trials but were less impaired by a switch in the platform location at the start of reversal learning. We discuss the possibility that these behavior discrepancies may be attributable to an enhancement in synaptic plasticity and loss of selectivity among synaptic pathways bearing different information into the CA1 region.