The Slack Channel Regulates Anxiety-Like Behaviors via Basolateral Amygdala Glutamatergic Projections to Ventral Hippocampus

Abstract

Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. In the present study, we find that the global Slack KO male mice exhibit anxious behaviors, whereas the Slack Y777H male mice manifest anxiolytic behaviors. The expression of Slack channels is rich in basolateral amygdala (BLA) glutamatergic neurons and downregulated in chronic corticosterone-treated mice. In addition, electrophysiological data show enhanced excitability of BLA glutamatergic neurons in the Slack KO mice and decreased excitability of these neurons in the Slack Y777H mice. Furthermore, the Slack channel deletion in BLA glutamatergic neurons is sufficient to result in enhanced avoidance behaviors, whereas Kcnt1 gene expression in the BLA or BLA-ventral hippocampus (vHPC) glutamatergic projections reverses anxious behaviors of the Slack KO mice. Our study identifies the role of the Slack channel in controlling anxious behaviors by decreasing the excitability of BLA-vHPC glutamatergic projections, providing a potential target for anxiolytic therapies.

Overexpression of EphB2 in the basolateral amygdala is crucial for inducing visceral pain sensitization in rats subjected to water avoidance stress

“…Furthermore, some other brain regions such as CeA, mPFC, or insular cortex may also participate in maintaining visceral hypersensitivity, 14 which merits further investigation. Besides, it is not surprising that inactivation of BLA abolished anxiety‐like behaviors due to its role as an integrative center in regulating anxiety responses 40 …”

“…Besides, it is not surprising that inactivation of BLA abolished anxiety-like behaviors due to its role as an integrative center in regulating anxiety responses. 40 The Eph RTKs family consists of 14 identified transmembrane proteins which are divided into EphA and EphB receptor subfamilies. Eph receptors localize mainly at both pre-and postsynapses and participate in not only brain development but also the regulation of synaptic functions.…”

“…Previous rodent studies in IBS mainly focused on CeA named as the “nociceptive amygdala,” which is critical in response to the hypothalamic–pituitary–adrenal axis 20,38 . Although BLA, a center for encoding negative emotions, was seldom investigated in visceral pain, 39 emerging evidence has shown that it is also involved in modulation of pain 18,40 . For example, BLA inputs to the medial prefrontal cortex (mPFC) are critical in pain and related cognitive deficits 41,42 .…”

“… 20 , 38 Although BLA, a center for encoding negative emotions, was seldom investigated in visceral pain, 39 emerging evidence has shown that it is also involved in modulation of pain. 18 , 40 For example, BLA inputs to the medial prefrontal cortex (mPFC) are critical in pain and related cognitive deficits. 41 , 42 The enhancement of long‐term depression at BLA‐CeA synapses is related to the pathogenesis of neuropathic pain and negative emotion.…”

“…Besides, it is not surprising that inactivation of BLA abolished anxiety‐like behaviors due to its role as an integrative center in regulating anxiety responses. 40 …”