Department of Neuroscience, Brown University, Providence, Rhode Island 02912.
Carney Institute for Brain Science, Brown University, Providence, Rhode Island 02912.
J Neurosci. 2022 Jun 1;42(22):4470-4487. doi: 10.1523/JNEUROSCI.2433-19.2022. Epub 2022 Apr 27.
The cortico-basal ganglia circuit is needed to suppress prepotent actions and to facilitate controlled behavior. Under conditions of response conflict, the frontal cortex and subthalamic nucleus (STN) exhibit increased spiking and theta band power, which are linked to adaptive regulation of behavioral output. The electrophysiological mechanisms underlying these neural signatures of impulse control remain poorly understood. To address this lacuna, we constructed a novel large-scale, biophysically principled model of the subthalamopallidal (STN-globus pallidus externus) network and examined the mechanisms that modulate theta power and spiking in response to cortical input. Simulations confirmed that theta power does not emerge from intrinsic network dynamics but is robustly elicited in response to cortical input as burst events representing action selection dynamics. Rhythmic burst events of multiple cortical populations, representing a state of conflict where cortical motor plans vacillate in the theta range, led to prolonged STN theta and increased spiking, consistent with empirical literature. Notably, theta band signaling required NMDA, but not AMPA, currents, which were in turn related to a triphasic STN response characterized by spiking, silence, and bursting periods. Finally, theta band resonance was also strongly modulated by architectural connectivity, with maximal theta arising when multiple cortical populations project to individual STN "conflict detector" units because of an NMDA-dependent supralinear response. Our results provide insights into the biophysical principles and architectural constraints that give rise to STN dynamics during response conflict, and how their disruption can lead to impulsivity and compulsivity. The subthalamic nucleus exhibits theta band power modulation related to cognitive control over motor actions during conditions of response conflict. However, the mechanisms of such dynamics are not understood. Here we developed a novel biophysically detailed and data-constrained large-scale model of the subthalamopallidal network, and examined the impacts of cellular and network architectural properties that give rise to theta dynamics. Our investigations implicate an important role for NMDA receptors and cortico-subthalamic nucleus topographical connectivities in theta power modulation.
皮质-基底神经节回路对于抑制优势动作和促进控制行为是必要的。在反应冲突的情况下，前额皮质和丘脑底核（STN）表现出更高的尖峰和θ频段功率，这与行为输出的适应性调节有关。这些冲动控制的神经特征的电生理机制仍知之甚少。为了解决这一空白，我们构建了一个新的、大规模的、基于生物物理原理的丘脑底核-苍白球外侧（STN-GPe）网络模型，并研究了调节皮质输入下θ频段功率和尖峰的机制。模拟结果证实，θ频段功率不是由内在网络动力学产生的，而是作为代表动作选择动力学的爆发事件，在对皮质输入的反应中被强烈诱发。多个皮质群体的节律性爆发事件，代表皮质运动计划在θ频段内波动的冲突状态，导致 STN 的θ频段延长和尖峰增加，这与实证文献一致。值得注意的是，θ频段信号需要 NMDA，但不需要 AMPA 电流，而后者又与 STN 的三相反应有关，其特征是尖峰、沉默和爆发期。最后，θ频段共振也强烈受到架构连接性的调制，当多个皮质群体由于 NMDA 依赖性超线性反应而投射到单个 STN“冲突检测器”单元时，会产生最大的θ频段。我们的研究结果为 STN 在反应冲突期间产生动力学的生物物理原理和架构约束提供了深入了解，并探讨了它们的破坏如何导致冲动和强迫。
丘脑底核在反应冲突期间表现出与认知控制运动动作相关的θ频段功率调制。然而，这种动力学的机制尚不清楚。在这里，我们开发了一种新的、基于生物物理细节和数据约束的丘脑底核网络的大规模模型，并研究了产生θ动力学的细胞和网络架构特性的影响。我们的研究结果表明，NMDA 受体和皮质-丘脑底核拓扑连接在θ频段功率调制中起着重要作用。
