Abstract
The serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN) is implicated in various mood- and emotion-related disorders, such as anxiety, fear and stress. Abnormal activity of DRN 5-HT neurons is the key factor in the development of these disorders. Here, we describe a crucial role for the Kv7.4 potassium channel in modulating DRN 5-HT neuronal excitability. We demonstrate that Kv7.4 is selectively expressed in 5-HT neurons of the DRN. Using selective Kv7.4 opener fasudil and Kv7.4 knock-out mice, we demonstrate that Kv7.4 is a potent modulator of DRN 5-HT neuronal excitability. Furthermore, we demonstrate that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4. The current study suggests a new strategy for treating psychiatric disorders related to altered activity of DRN 5-HT neurons using K+ channel modulators.
Highlights
The serotonergic (5-HT) system originating in the dorsal raphe nucleus (DRN) is involved in regulating various physiological and behavioral functions, including mood- and emotionrelated behaviors (Michelsen et al, 2008; Olivier, 2015)
The results show that Kv7.4 positive neurons accounted for approximately 67% of the 5-HT neurons in the DRN (Figure 1C)
The electrophysiological recordings were made on the neurons located on the midline in the ventromedial subdivision of the DRN which is most densely populated by 5-HT neurons (Paxinos and Watson, 2007; Gocho et al, 2013)
Summary
The serotonergic (5-HT) system originating in the dorsal raphe nucleus (DRN) is involved in regulating various physiological and behavioral functions, including mood- and emotionrelated behaviors (Michelsen et al, 2008; Olivier, 2015). Aversive stimuli-produced stress, anxiety and fear increase neuronal activity in subpopulations of serotonergic neurons and increase serotonin levels in the vicinity of DRN neurons (Amat et al, 2005). Activity of the 5-HT neurons needs to be well controlled to maintain emotional homeostasis. For 5-HT neurons, some K+ channels, including SK channels (Crespi, 2010; Sargin et al, 2016), TREK1 channels (Ye et al, 2015) and Kir3/GIRK channels (Llamosas et al, 2015, 2017; Montalbano et al, 2015) have been suggested as playing important roles in controlling the intrinsic neuronal activity, and modulating these channels may alleviate emotional disorders. Up-regulation of SK3 channels in serotoninproducing neurons are responsible for greatly reduced activity in these neurons from a model of
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