Chang Isaac Y M, Paz Jeanne T
Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, California, United States.
Neuroscience Graduate Program, University of California San Francisco, San Francisco, California, United States.
J Neurophysiol. 2025 Apr 1;133(4):1329-1340. doi: 10.1152/jn.00052.2025. Epub 2025 Mar 25.
Numerous cortical and subcortical inputs innervate the thalamus and robustly control thalamic activity. These synaptic inputs differ in shape and undergo dynamic changes throughout development and disease conditions. How the shape of postsynaptic currents regulates thalamic neuronal firing has been studied mainly in young rodents with immature neural development and function. Here, we use adult mice with mature intrinsic excitability to address this question in two compartments of the thalamus-the nucleus reticularis thalami (nRT) and thalamocortical (TC) relay nuclei. Using whole cell patch-clamp electrophysiology, we simulated synthetic inhibitory (IPSCs) and synthetic excitatory postsynaptic currents (EPSCs), injected them in nRT and TC neurons, and examined how changes in their shape parameters regulated neuronal firing in different electrical states. We found that in response to synthetic IPSCs, TC neurons initiate low-threshold spikes (LTSs) earlier than nRT neurons, and the amplitude of IPSCs regulates the probability of initiating an LTS while the duration of IPSCs regulates the timing at which the LTS initiates. These results show that in the adult thalamus, LTS is regulated by IPSCs similarly to what has been reported for the immature thalamus. In addition, sharp driver-like EPSCs evoke more firing when nRT and TC neurons are silent; whereas slow modulator-like EPSCs evoke more firing when nRT and TC neurons are active. Critically, we have generated a quantitative map of how features of synaptic currents shape neuronal firing in relationship with activity states. We provide a systematic overview of how the shape parameters (i.e., amplitude, duration, and charge) of synthetic inhibitory and excitatory synaptic currents regulate neuronal firing in the adult murine thalamus across cell types (nRT vs. TC neurons) and electrical states (active vs. silent).
大量皮质和皮质下输入支配丘脑并有力地控制丘脑活动。这些突触输入在形态上存在差异，并且在整个发育过程和疾病状态中会发生动态变化。突触后电流的形态如何调节丘脑神经元的放电，主要是在神经发育和功能不成熟的幼年啮齿动物中进行研究的。在这里，我们使用具有成熟内在兴奋性的成年小鼠，在丘脑的两个区域——丘脑网状核（nRT）和丘脑皮质（TC）中继核中解决这个问题。我们采用全细胞膜片钳电生理学方法，模拟了合成抑制性突触后电流（IPSCs）和合成兴奋性突触后电流（EPSCs），将它们注入nRT和TC神经元，并研究其形态参数的变化如何在不同电状态下调节神经元放电。我们发现，对于合成IPSCs，TC神经元比nRT神经元更早地引发低阈值尖峰（LTSs），IPSCs的幅度调节引发LTS的概率，而IPSCs的持续时间调节LTS引发的时间。这些结果表明，在成年丘脑中，LTS受IPSCs的调节方式与未成熟丘脑的情况类似。此外，当nRT和TC神经元处于静息状态时，尖锐的驱动样EPSCs会引发更多放电；而当nRT和TC神经元处于活动状态时，缓慢的调制样EPSCs会引发更多放电。至关重要的是，我们已经生成了一个关于突触电流特征如何与活动状态相关联地塑造神经元放电的定量图谱。我们系统地概述了合成抑制性和兴奋性突触电流的形态参数（即幅度、持续时间和电荷量）如何在成年小鼠丘脑中跨细胞类型（nRT与TC神经元）和电状态（活动与静息）调节神经元放电。
