Our understanding of depression and its treatment has advanced with the advent of ketamine as a rapid-acting antidepressant and the development and refinement of tools capable of selectively altering the activity of populations of neuronal subtypes. This work has resulted in a paradigm shift away from dysregulation of single neurotransmitter systems in depression towards circuit level abnormalities impacting function across multiple brain regions and neurotransmitter systems. Studies on the features of circuit level abnormalities demonstrate structural changes within the prefrontal cortex (PFC) and functional changes in its communication with distal brain structures. Treatments that impact the activity of brain regions, such as transcranial magnetic stimulation or rapid-acting antidepressants like ketamine, appear to reverse depression associated circuit abnormalities though the mechanisms underlying the reversal, as well as development of these abnormalities remains unclear. Recently developed optogenetic and chemogenetic tools that allow high-fidelity control of neuronal activity in preclinical models have begun to elucidate the contributions of the PFC and its circuitry to depression- and anxiety-like behavior. These tools offer unprecedented access to specific circuits and neuronal subpopulations that promise to offer a refined view of the circuit mechanisms surrounding depression and potential mechanistic targets for development and reversal of depression associated circuit abnormalities.

中文翻译：

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抑郁和焦虑症中的前额叶皮层回路：离散神经元群体和目标区域的贡献。

随着氯胺酮作为一种快速作用的抗抑郁药的出现以及对能够选择性改变神经元亚型群体活动的工具的开发和完善，我们对抑郁症及其治疗的认识不断提高。这项工作导致范式从抑郁中的单个神经递质系统失调转移到影响多个大脑区域和神经递质系统功能的电路水平异常。对电路水平异常特征的研究表明前额叶皮层（PFC）内的结构变化及其与远端大脑结构的通讯功能发生变化。影响大脑区域活动的治疗，例如经颅磁刺激或速效抗抑郁药（如氯胺酮）尽管逆转的潜在机制以及这些异常的发展仍不清楚，但似乎可以逆转与抑郁相关的电路异常。最近开发的允许在临床前模型中高保真地控制神经元活动的光遗传学和化学遗传学工具已经开始阐明PFC及其电路对抑郁和焦虑样行为的贡献。这些工具为特定的回路和神经元亚群提供了前所未有的访问权限，有望为围绕抑郁症的回路机制以及潜在的机械性靶标提供完善的视图，从而开发和逆转与抑郁症相关的回路异常。最近开发的允许在临床前模型中高保真地控制神经元活动的光遗传学和化学遗传学工具已经开始阐明PFC及其电路对抑郁和焦虑样行为的贡献。这些工具为特定的回路和神经元亚群提供了前所未有的访问权限，有望为围绕抑郁症的回路机制以及潜在的机械性靶标提供完善的视图，从而开发和逆转与抑郁症相关的回路异常。最近开发的允许在临床前模型中高保真地控制神经元活动的光遗传学和化学遗传学工具已经开始阐明PFC及其电路对抑郁和焦虑样行为的贡献。这些工具为特定的回路和神经元亚群提供了前所未有的访问权限，有望为围绕抑郁症的回路机制以及潜在的机械性靶标提供完善的视图，从而开发和逆转与抑郁症相关的回路异常。