Codianni Marcello G, Rubin Jonathan E
Department of Mathematics, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
Center for the Neural Basis of Cognition, Pittsburgh, PA, 15260, USA.
Brain Struct Funct. 2023 Mar;228(2):589-611. doi: 10.1007/s00429-022-02604-9. Epub 2023 Jan 18.
Cholinergic interneurons in the striatum, also known as tonically active interneurons or TANs, are thought to have a strong effect on corticostriatal plasticity and on striatal activity and outputs, which in turn play a critical role in modulating downstream basal ganglia activity and movement. Striatal TANs can exhibit a variety of firing patterns and responses to synaptic inputs; furthermore, they have been found to display various surges and pauses in activity associated with sensory cues and reward delivery in learning as well as with motor tic production. To help explain the factors that contribute to TAN activity patterns and to provide a resource for future studies, we present a novel conductance-based computational model of a striatal TAN. We show that this model produces the various characteristic firing patterns observed in recordings of TANs. With a single baseline tuning associated with tonic firing, the model also captures a wide range of TAN behaviors found in previous experiments involving a variety of manipulations. In addition to demonstrating these results, we explain how various ionic currents in the model contribute to them. Finally, we use this model to explore the contributions of the acetylcholine released by TANs to the production of surges and pauses in TAN activity in response to strong excitatory inputs. These results provide predictions for future experimental testing that may help with efforts to advance our understanding of the role of TANs in reinforcement learning and in motor disorders such as Tourette's syndrome.
纹状体内的胆碱能中间神经元，也被称为紧张性活动中间神经元或TANs，被认为对皮质纹状体可塑性、纹状体活动及输出有强大影响，而这反过来又在调节下游基底神经节活动和运动中起关键作用。纹状体TANs可表现出多种放电模式及对突触输入的反应；此外，人们发现它们在学习过程中与感觉线索和奖励传递相关的活动中，以及在运动性抽搐产生时，会出现各种活动激增和暂停。为帮助解释促成TAN活动模式的因素，并为未来研究提供资源，我们提出了一种新型的基于电导的纹状体TAN计算模型。我们表明，该模型产生了在TAN记录中观察到的各种特征性放电模式。通过与紧张性放电相关的单一基线调谐，该模型还捕捉到了先前实验中在各种操作下发现的广泛的TAN行为。除了展示这些结果，我们还解释了模型中的各种离子电流是如何促成这些结果的。最后，我们使用该模型来探索TANs释放的乙酰胆碱对TAN活动中响应强兴奋性输入时的激增和暂停产生的贡献。这些结果为未来的实验测试提供了预测，可能有助于推进我们对TANs在强化学习和诸如妥瑞氏综合征等运动障碍中作用的理解。
