Abnormal 5-HT modulation of stress behaviors in the Kv4.2 knockout mouse.
The Kv4.2 gene codes for an essential subunit of voltage-gated A-type potassium channels that are involved in dendritic signal integration and synaptic plasticity. Detailed cellular characterization in CA1 pyramidal neurons of the hippocampus has shown that knocking out the Kv4.2 gene increases neuronal excitability and promotes long-term potentiation. However, the overall behavioral consequences of these modifications have not been fully explored. Given the growing connection between neuronal plasticity and affect processing in the hippocampus and other Kv4.2 expressing regions, we proposed to investigate whether the absence of this gene would alter the stress response of mice to the forced swimming and tail suspension tests (TSTs) for depression-like behavior. Kv4.2 knockout (KO) mice, generated in the 129SvEv background, demonstrated elevated immobility and a loss of swimming, as well as antidepressant resistance to the selective 5-HT reuptake inhibitor fluoxetine (FLX). Characterization of a relatively new head movement behavior category, responsive to serotonergic treatment in wildtype (WT) mice, supported conclusions of abnormal 5-HT modulation. Electrophysiology recordings in the prefrontal cortex showed a blunting of postsynaptic response to direct 5-HT application following a single period of swim stress only in the animals without the Kv4.2 subunit. Based on our findings, we hypothesize that Kv4.2 KO mice may have an exaggerated 5-HT response to stress leading to a premature desensitization of postsynaptic receptors and a loss of continued behavior modulation. These results may shed some light on the involvement of A-type potassium channels in the effective action of selective serotonin reuptake inhibitor (SSRI) antidepressants.
Lockridge
A
A
Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA.
Su
J
J
Yuan
L L
LL
D000818:Animals; D001522:Behavior, Animal; D005473:Fluoxetine / Q000494:pharmacology; D006257:Head / Q000503:physiopathology; D007650:Ketanserin / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009068:Movement; D017397:Prefrontal Cortex / Q000503:physiopathology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D051672:Shal Potassium Channels / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology / Q000523:psychology*
D005473:Fluoxetine; D007650:Ketanserin; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D051672:Shal Potassium Channels