Department of Psychiatry, Emory University, and Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes NPRC, 954 Gatewood Road, Atlanta, GA, 30329, USA.
Department of Psychiatry, Emory University, and Division of Behavioral Neuroscience and Psychiatric Disorders, Yerkes NPRC, 954 Gatewood Road, Atlanta, GA, 30329, USA.
Neuropharmacology. 2019 May 15;150:80-90. doi: 10.1016/j.neuropharm.2019.03.013. Epub 2019 Mar 14.
Distinct regions and cell types in the anterolateral group of the bed nucleus of the stria terminalis (BNST) act to modulate anxiety in opposing ways. A history of chronic stress increases anxiety-like behavior with lasting electrophysiological effects on the BNST. However, the opposing circuits within the BNST suggest that stress may have differential effects on the individual cell types that comprise these circuits to shift the balance to favor anxiogenesis. Yet, the effects of stress are generally examined by treating all neurons within a particular region of the BNST as a homogenoeus population. We used patch-clamp electrophysiology and single-cell quantitative reverse transcriptase PCR (scRT-PCR) to determine how chronic shock stress (CSS) affects electrophysiological and neurochemical properties of Type I, Type II, and Type III neurons in the BNST. We report that CSS resulted in changes in the input resistance, time constant, action potential waveform, and firing rate of Type III but not Type I or II neurons. Additionally, only the Type III neurons exhibited an increase in Crf mRNA and a decrease in striatal-enriched protein tyrosine phosphatase (Ptpn5) mRNA after CSS. In contrast, only non-Type III cells showed a reduction in calcium-permeable AMPA receptor (CP-AMPAR) current and changes in mRNA expression of genes encoding AMPA receptor subunits after CSS. Importantly, none of the effects of CSS observed were seen in all cell types. Our results suggest that Type III neurons play a unique role in the BNST circuit and represent a population of CRF neurons particularly sensitive to chronic stress.
终纹床核前外侧群中的不同区域和细胞类型以相反的方式调节焦虑。慢性应激的历史会增加焦虑样行为，并对 BNST 产生持久的电生理影响。然而，BNST 中的相反回路表明，应激可能对构成这些回路的单个细胞类型产生不同的影响，从而使平衡有利于焦虑的产生。然而，应激的影响通常通过将 BNST 特定区域内的所有神经元视为均质群体来进行检查。我们使用膜片钳电生理学和单细胞定量逆转录 PCR（scRT-PCR）来确定慢性休克应激（CSS）如何影响 BNST 中 I 型、II 型和 III 型神经元的电生理和神经化学特性。我们报告说，CSS 导致 III 型神经元的输入电阻、时间常数、动作电位波形和放电率发生变化，但 I 型或 II 型神经元没有变化。此外，只有 III 型神经元在 CSS 后表现出 Crf mRNA 的增加和纹状体丰富的蛋白酪氨酸磷酸酶（Ptpn5）mRNA 的减少。相比之下，只有非 III 型细胞显示 CP-AMPAR 电流减少和编码 AMPA 受体亚基的基因的 mRNA 表达变化后 CSS。重要的是，CSS 观察到的所有影响都没有在所有细胞类型中看到。我们的结果表明，III 型神经元在 BNST 回路中发挥独特作用，代表对慢性应激特别敏感的 CRF 神经元群体。
