Activity-dependent organization of prefrontal hub-networks for associative learning and signal transformation

Activity-dependent organization of prefrontal hub-networks for associative learning and signal transformation
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用于联想学习和信号转换的前额叶中枢网络的活动依赖组织

DOI:
10.1101/2021.08.31.458461
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发表时间:
2021
期刊:
bioRxiv
影响因子:
--
通讯作者:
Nagai Takeharu
Nagai Takeharu
中科院分区:
--
文献类型:
--
作者:
Agetsuma Masakazu;Sato Issei;Tanaka Yasuhiro R;Carrillo-Reid Luis;Kasai Atsushi;Arai Yoshiyuki;Yoshitomo Miki;Inagaki Takashi;Hashimoto Hitoshi;Nabekura Junichi;Nagai Takeharu

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联想学习对于适应环境变化至关重要。涉及背内侧前额叶皮层(dmPFC)的神经元群体之间的相互作用被提出来调节联想学习,但这些神经元群体如何存储和处理有关该协会的信息仍不清楚。在这里,我们开发了一个管道,用于在恐惧条件反射过程中对雄性小鼠dmPFC中的神经群体活动进行纵向双光子成像和计算解剖,使我们能够检测dmPFC网络拓扑结构中的学习依赖性变化。使用正则化回归方法和图形建模,我们发现,恐惧条件反射驱动dmPFC重组,产生一个神经元合奏编码条件反应(CR),其特征在于增强内部的协同性,功能连接,并与条件刺激(CS)的关联。重要的是,神经元强烈响应于非条件刺激条件随后成为枢纽的这种新的联想网络的CS到CR的转换。总之,我们证明了学习依赖的动态调制人口编码结构上的活动依赖形成的枢纽网络内的dmPFC。
Associative learning is crucial for adapting to environmental changes. Interactions among neuronal populations involving the dorso-medial prefrontal cortex (dmPFC) are proposed to regulate associative learning, but how these neuronal populations store and process information about the association remains unclear. Here we developed a pipeline for longitudinal two-photon imaging and computational dissection of neural population activities in male mouse dmPFC during fear-conditioning procedures, enabling us to detect learning-dependent changes in the dmPFC network topology. Using regularized regression methods and graphical modeling, we found that fear conditioning drove dmPFC reorganization to generate a neuronal ensemble encoding conditioned responses (CR) characterized by enhanced internal coactivity, functional connectivity, and association with conditioned stimuli (CS). Importantly, neurons strongly responding to unconditioned stimuli during conditioning subsequently became hubs of this novel associative network for the CS-to-CR transformation. Altogether, we demonstrate learning-dependent dynamic modulation of population coding structured on the activity-dependent formation of the hub network within the dmPFC.
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