Input Zone-Selective Dysrhythmia in Motor Thalamus after Dopamine Depletion.
Input Zone-Selective Dysrhythmia in Motor Thalamus after Dopamine Depletion.
复制标题
多巴胺耗竭后运动丘脑输入区选择性心律失常。
DOI：
10.1523/jneurosci.1753-21.2021
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发表时间：
2021-12-15
期刊：
影响因子：
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通讯作者：
Magill PJ
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文献类型：
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作者：
Nakamura KC;Sharott A;Tanaka T;Magill PJ
大脑皮层、基底节和运动丘脑形成对有目的运动很重要的回路。在帕金森病患者中，基底节神经元经常在皮层以大脑状态依赖的方式出现慢波(∼1赫兹)和β频段(15-30赫兹)振荡时表现出节律失常的活动。然而，仍然迫切需要阐明与帕金森氏症相关的多巴胺耗竭后，丘脑运动活动变得类似节律紊乱的程度。为了解决这一问题，我们记录了麻醉雄性多巴胺完整大鼠和6-羟色胺损毁大鼠在两种大脑状态下运动丘脑的基底节接受区(BZ)和小脑接受区(CZ)的单个神经元和整体输出，这两种状态分别由皮质慢波活动和激活定义。多巴胺耗竭后表现出两种形式的丘脑输入区选择性心律失常：(1)BZ神经元，而不是CZ神经元，相对于慢波活动中普遍存在的皮质慢振荡，表现出异常的相移放电；(2)BZ神经元，但不是CZ神经元，不适当地同步它们的放电，并参与激活状态下产生的夸大的皮质β振荡。这些节律紊乱并不伴随典型的帕金森病基于放电频率的回路组织模型所预测的丘脑活动不足。对黑质网状部神经元的互补记录表明，它们活动动力学的改变可能是BZ节律失常的基础。最后，药理学研究表明，运动丘脑中持续的活动增强了运动皮质中的β振荡。我们的结论是，BZ神经元被选择性地启动，以介导异常的慢节奏和β频段节律对帕金森病电路信息处理的不利影响。意义陈述运动丘脑神经元介导基底节和小脑对大脑皮层的影响以控制运动。基底节多巴胺的慢性消耗会导致帕金森氏症的一些症状。在这里，我们阐明了多巴胺耗竭如何改变运动丘脑神经元参与体内皮质-基底神经节回路中出现的两种不同振荡的方式。我们发现，在多巴胺耗尽后，接受基底神经节输入的丘脑区的神经元特别容易变得节律失常，改变其动作电位放电的相位和/或同步(但不是速率)。这会导致大脑皮层节律不齐。我们的结果为帕金森病患者运动丘脑特定部分的异常节律如何有害地影响神经回路动力学和行为提供了重要的新见解。
The cerebral cortex, basal ganglia and motor thalamus form circuits important for purposeful movement. In Parkinsonism, basal ganglia neurons often exhibit dysrhythmic activity during, and with respect to, the slow (∼1 Hz) and beta-band (15-30 Hz) oscillations that emerge in cortex in a brain state-dependent manner. There remains, however, a pressing need to elucidate the extent to which motor thalamus activity becomes similarly dysrhythmic after dopamine depletion relevant to Parkinsonism. To address this, we recorded single-neuron and ensemble outputs in the basal ganglia-recipient zone (BZ) and cerebellar-recipient zone (CZ) of motor thalamus in anesthetized male dopamine-intact rats and 6-OHDA-lesioned rats during two brain states, respectively defined by cortical slow-wave activity and activation. Two forms of thalamic input zone-selective dysrhythmia manifested after dopamine depletion: (1) BZ neurons, but not CZ neurons, exhibited abnormal phase-shifted firing with respect to cortical slow oscillations prevalent during slow-wave activity; and (2) BZ neurons, but not CZ neurons, inappropriately synchronized their firing and engaged with the exaggerated cortical beta oscillations arising in activated states. These dysrhythmias were not accompanied by the thalamic hypoactivity predicted by canonical firing rate-based models of circuit organization in Parkinsonism. Complementary recordings of neurons in substantia nigra pars reticulata suggested that their altered activity dynamics could underpin the BZ dysrhythmias. Finally, pharmacological perturbations demonstrated that ongoing activity in the motor thalamus bolsters exaggerated beta oscillations in motor cortex. We conclude that BZ neurons are selectively primed to mediate the detrimental influences of abnormal slow and beta-band rhythms on circuit information processing in Parkinsonism. SIGNIFICANCE STATEMENT Motor thalamus neurons mediate the influences of basal ganglia and cerebellum on the cerebral cortex to govern movement. Chronic depletion of dopamine from the basal ganglia causes some symptoms of Parkinson's disease. Here, we elucidate how dopamine depletion alters the ways motor thalamus neurons engage with two distinct oscillations emerging in cortico-basal ganglia circuits in vivo. We discovered that, after dopamine depletion, neurons in the thalamic zone receiving basal ganglia inputs are particularly prone to becoming dysrhythmic, changing the phases and/or synchronization (but not rate) of their action potential firing. This bolsters cortical dysrhythmia. Our results provide important new insights into how aberrant rhythmicity in select parts of motor thalamus could detrimentally affect neural circuit dynamics and behavior in Parkinsonism.