Effects of genetic deletion of the Kv4.2 voltage-gated potassium channel on murine anxiety-, fear- and stress-related behaviors

In this paper, we analyzed the phenotype Kv4.2 knockout mice based on their neurological function, on a battery of behaviors including those related to anxiety and depression, and on plasticity-related learning tasks.We found a novelty-induced hyperactive phenotype in knockout mice, and these mice also displayed increased reactivity to novel stimulus such as an auditory tone. No clear anxiety- or depression-related phenotype was observed, nor any alterations in learning/plasticity-based paradigms.We did not find clear evidence for an involvement of Kv4.2 in neuropsychiatric or plasticity-related phenotypes, but there was support for a role in Kv4.2 in dampening excitatory responses to novel stimuli.The excitability and functional plasticity of specific brain circuits in cortical, limbic, and midbrain regions is thought to mediate behavioral responses to environmental threats, and to enable adaptation to stressors. At the cellular level, voltage- and calcium-activated potassium (K+) channels provide an important means of modulating neuronal activity and synaptic plasticity. Their function is further refined via the presence of multiple Kv primary and auxiliary subunits that differ in their voltage-dependence, post-translational regulation, sub-cellular localization and regional pattern of expression in the brain to accomplish distinct physiological functions.A-type K+ channels composed of Kv4 subunits transmit a rapidly activating and inactivating current [1]. Kv4.2 mRNA is expressed in the periphery and in various brain regions involved in mediating stress-related behaviors, including the medial prefrontal cortex (mPFC), hippocampus and hypothalamus [2]. In CA1 hippocampal neurons, Kv4.2 protein is primarily localized on dendrites [3] where they exert their strongest functional effects [4]. Gene deletion of Kv4.2 (Kcnd2) in mice eliminates most of the A-type K+ current in hippocampal and cortical neurons [5-7], and increases back-propagation of the action potential