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

• Main Authors: Derya Sargin, David K Oliver, Evelyn K Lambe
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2016-11-01
• Series: eLife
• Subjects: dorsal raphe; serotonin neurons; social isolation; calcium-activated potassium channels; SK3; depressive-like behaviors
• Online Access: https://elifesciences.org/articles/21416

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.