Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels

eLife

Derya Sargin¹  David K Oliver¹  Evelyn K Lambe¹ 

[1] Department of Physiology, University of Toronto, Toronto, Canada;

关键词: dorsal raphe;    serotonin neurons;    social isolation;    calcium-activated potassium channels;    SK3;    depressive-like behaviors;   

DOI  :  10.7554/eLife.21416

来源: DOAJ

【 摘 要 】

The activity of serotonin (5-HT) neurons is critical for mood regulation. In a mouse model of chronic social isolation, a known risk factor for depressive illness, we show that 5-HT neurons in the dorsal raphe nucleus are less responsive to stimulation. Probing the responsible cellular mechanisms pinpoints a disturbance in the expression and function of small-conductance Ca2+-activated K+ (SK) channels and reveals an important role for both SK2 and SK3 channels in normal regulation of 5-HT neuronal excitability. Chronic social isolation renders 5-HT neurons insensitive to SK2 blockade, however inhibition of the upregulated SK3 channels restores normal excitability. In vivo, we demonstrate that inhibiting SK channels normalizes chronic social isolation-induced anxiety/depressive-like behaviors. Our experiments reveal a causal link for the first time between SK channel dysregulation and 5-HT neuron activity in a lifelong stress paradigm, suggesting these channels as targets for the development of novel therapies for mood disorders.

【 授权许可】

Unknown