Zhang Lang-Qian, Yao Juan, Gao Jie, Sun Lin, Wang Li-Ting, Sui Jian-Feng
Experimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, PR China; Department of Medical Technology, Chongqing Medical and Pharmaceutical College, 82 University City Road, Shapingba District, Chongqing 401331, PR China.
Experimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing 400038, PR China.
Behav Brain Res. 2019 Feb 1;359:149-155. doi: 10.1016/j.bbr.2018.10.035. Epub 2018 Oct 29.
Classical eyeblink conditioning (EBC) is one of the simplest forms of associative learning that depends critically on the cerebellum. Using delay EBC (dEBC), a standard paradigm in which the unconditioned stimulus (US) is delayed and co-terminates with the conditioned stimulus (CS), converging lines of evidence has been accumulated and shows that the essential neural circuit mediating EBC resides in the cerebellum and brainstem. In addition to this essential circuit, multiple cerebral cortical and subcortical structures are required to modulate dEBC with suboptimal training parameters, and trace EBC (tEBC) in which a trace-interval separates the CS and US. However, it remains largely unclear why and how so many brain regions are involved for modulation of EBC. Previous research has suggested that the forebrain regions, such as medial prefrontal cortex (mPFC) and hippocampus, may be required to process weak CSs, or to realize temporal overlap between the CS and US signal inputs when the two stimuli were separated in time (i.e. during tEBC). Here, we proposed a multi-level network model for EBC modulation which focuses on sensory processing of CS. The model explains how different neural pathways projecting to pontine nucleus (PN) are involved to amplify or extend CS through heterosynaptic facilitation mechanism or "substitution effect" under different circumstances to achieve EBC. As such, our model can serve as a general framework to explain the modulating mechanism of EBC in a variety of conditions and to help understand the interaction among cerebellum, brainstem, cortical and subcortical regions in EBC modulation.
经典眨眼条件反射（EBC）是联想学习中最简单的形式之一，它严重依赖小脑。使用延迟EBC（dEBC）这种标准范式，即无条件刺激（US）被延迟并与条件刺激（CS）同时终止，已经积累了越来越多的证据表明，介导EBC的基本神经回路位于小脑和脑干中。除了这个基本回路外，还需要多个大脑皮层和皮层下结构，以次优训练参数来调节dEBC，以及调节痕迹EBC（tEBC，其中CS和US之间有一个痕迹间隔）。然而，目前仍不清楚为什么以及如此多的脑区如何参与EBC的调节。先前的研究表明，前脑区域，如内侧前额叶皮层（mPFC）和海马体，可能需要处理较弱的CS，或者当两个刺激在时间上分开时（即在tEBC期间）实现CS和US信号输入之间的时间重叠。在这里，我们提出了一个用于EBC调节的多层次网络模型，该模型侧重于CS的感觉处理。该模型解释了投射到脑桥核（PN）的不同神经通路如何在不同情况下通过异突触易化机制或“替代效应”参与放大或延长CS，以实现EBC。因此，我们的模型可以作为一个通用框架，来解释各种条件下EBC的调节机制，并有助于理解小脑、脑干、皮层和皮层下区域在EBC调节中的相互作用。
