Abstract
INTRODUCTION: The two-pore domain potassium channel TREK-1 is a member of background K(+) channels that are thought to provide baseline regulation of membrane excitability. Recent studies have highlighted the putative role of TREK-1 in the action of antidepressants, and its antagonists might be potentially effective antidepressants. However, the mechanisms underlying the actions of TREK-1 are not yet fully understood. METHODS: The expression of TREK-1 was examined in a mouse model of chronic unpredictable mild stress (CUMS) using immunoblotting. Neuron-specific genetic manipulation of TREK-1 was performed through adeno-associated virus. Behavioral tests were performed to evaluate depression-related behaviors. Electrophysiological recordings were used to evaluate synaptic plasticity. Golgi staining was used to examine neuroplasticity. RESULTS: TREK-1 expression was increased in the mouse hippocampus after CUMS. Knockdown of TREK-1 in hippocampal neurons significantly attenuated depressive-like behaviors and prevented the decrease of CUMS-induced synaptic proteins in mice. Further examination indicated that neuron-specific knockdown of TREK-1 in the hippocampus prevented stress-induced impairment of glutamatergic synaptic transmission in the CA1 region. Moreover, chronic TREK-1 inhibition protected against CUMS-induced depressive-like behaviors and impairment of synaptogenesis in the hippocampus. CONCLUSION: Our results indicate a role for TREK-1 in the modulation of synaptic plasticity in a mouse model of depression. These findings will provide insight into the pathological mechanism of depression and further evidence for a novel target for antidepressant treatment.