慢性应激通过增加直接通路神经元的兴奋驱动来促进基底神经节的去抑制

IF 4.3 2区 医学 Q1 NEUROSCIENCES Neurobiology of Stress Pub Date : 2023-09-22 DOI:10.1016/j.ynstr.2023.100571
Diana Rodrigues , Patricia Monteiro
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引用次数: 0

摘要

慢性压力(CS)是公认的强迫症(OCD)和抽动秽语综合征(TS)的触发因素,这两种神经精神疾病的特征是存在刻板的运动症状。运动动作的计划和执行由背侧纹状体控制,背侧纹状体是一个大脑区域,通过分别从直接或间接途径激活纹状体神经元来促进或抑制运动。尽管背侧纹状体在运动障碍和CS暴露中受到影响,但CS如何影响两种相反的途径尚不完全清楚。在这里,我们报道了CS在小鼠中选择性地增强直接途径,同时保留间接途径。具体而言,我们发现CS既增加了对背内侧纹状体(DMS)直接通路神经元的兴奋,又减少了对其的抑制。此外,位于DMS中的抑制性中间神经元在慢性应激后也表现出兴奋性驱动减弱,从而增强纹状体的去抑制作用。总之,我们提出了一个模型,在该模型中,纹状体中兴奋性驱动的增加和抑制性驱动的减少都会导致基底神经节运动直接通路的去抑制,这一机制可能解释了压力下运动刻板印象和抽动障碍的出现。
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Chronic stress promotes basal ganglia disinhibition by increasing the excitatory drive of direct-pathway neurons

Chronic stress (CS) is a well-recognized triggering factor in obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS), two neuropsychiatric disorders characterized by the presence of stereotypic motor symptoms. Planning and execution of motor actions are controlled by the dorsal striatum, a brain region that promotes or suppresses motor movement by activating striatal neurons from the direct- or indirect-pathway, respectively. Despite the dorsal striatum being affected in motor disorders and by CS exposure, how CS affects the two opposing pathways is not fully understood. Here, we report that CS in mice selectively potentiates the direct-pathway, while sparing the indirect-pathway. Specifically, we show that CS both increases excitation and reduces inhibition over direct-pathway neurons in the dorsomedial striatum (DMS). Furthermore, inhibitory interneurons located in the DMS also display reduced excitatory drive after chronic stress, thus amplifying striatal disinhibition. Altogether, we propose a model where both increased excitatory drive and decreased inhibitory drive in the striatum causes disinhibition of basal ganglia's motor direct pathway - a mechanism that might explain the emergence of motor stereotypies and tic disorders under stress.

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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
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