PDF(Pubmed)
Abstract：
Inhibitory parvalbumin (PV) interneurons regulate the activity of neural circuits within brain regions involved in emotional processing, including the prefrontal cortex (PFC). Recently, rodent studies have implicated a stress-induced increase in prefrontal PV neuron activity in the development of anxiety behaviors, particularly in females. However, the mechanisms through which stress increases activity of prefrontal PV neurons remain unknown. The fast-spiking properties of PV neurons in part come from their expression of voltage-gated potassium (K+) ion channels, particularly Kv3.1 channels. We therefore suggest that stress-induced changes in Kv3.1 channels contribute to the appearance of an anxious phenotype following chronic stress in female mice. Here, we first showed that unpredictable chronic mild stress (UCMS) increased expression of Kv3.1 channels on prefrontal PV neurons in female mice, a potential mechanism underlying the previously observed hyperactivity of these neurons after stress. We then showed that female mice deficient in Kv3.1 channels displayed resilience to UCMS-induced anxiety-like behaviors. Altogether, our findings implicate Kv3.1 channels in the development of anxiety-like behaviors following UCMS, particularly in females, providing a novel mechanism to understand sex-specific vulnerabilities to stress-induced psychopathologies.
摘要：
抑制性小白蛋白（PV）中间神经元调节参与情绪处理的大脑区域内神经回路的活动，包括前额叶皮层（PFC）。最近,啮齿动物的研究表明，在焦虑行为的发展过程中，压力引起的前额叶PV神经元活动增加，尤其是女性。然而,应激增加前额叶PV神经元活动的机制尚不清楚。PV神经元的快速尖峰特性部分来自其电压门控钾（K）离子通道的表达，特别是Kv3.1频道。因此，我们建议应激诱导的Kv3.1通道变化有助于雌性小鼠慢性应激后出现焦虑表型。这里,我们首先表明，不可预测的慢性轻度应激（UCMS）增加了雌性小鼠前额叶PV神经元上Kv3.1通道的表达，先前观察到的这些神经元在应激后过度活跃的潜在机制。然后，我们发现缺乏Kv3.1通道的雌性小鼠对UCMS诱导的焦虑样行为表现出弹性。总之,我们的发现暗示Kv3.1通道在UCMS后焦虑样行为的发展，尤其是女性，提供了一种新的机制来了解性别对压力诱发的精神病理学的脆弱性。
