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接受背内侧丘脑投射的前额叶皮层锥体神经元的电生理学和形态学特性(英文)

范祖权, 陶晓冬, 魏亚茹, 张雪寒^*

复旦大学脑科学研究院，医学神经生物学国家重点实验室，教育部脑科学前沿中心，上海 200032

摘要

脑高级功能对生物体的生存至关重要。内侧前额叶皮层(medial prefrontal cortex, mPFC)和背内侧丘脑(mediodorsal thalamus, MD)之间存在的密集交互投射在多种认知功能和执行功能的调控中发挥重要作用。根据神经元的形态学和电生理学特性，mPFC的锥体神经元已被分成多种亚类，但是特定神经环路的mPFC神经元的形态学和电生理学特性尚不清楚。本文旨在研究mPFC中接受MD投射的锥体神经元的形态学和电生理学特性。在过去，研究神经元的形态学和电生理学特性主要依赖大量的神经元电生理记录和其形态重构，但是在研究特定神经环路的神经元电生理和形态学特性时，这种方法效率较低。针对这一不足，本研究将传统形态学和电生理学方法与聚类分析等机器学习的方法相结合，建立mPFC锥体神经元形态学和电生理特性的分类模型。采用神经环路跨突触示踪策略标记mPFC中接受MD投射的锥体神经元，应用全细胞膜片钳记录和神经元重构技术获取mPFC中接受MD投射的锥体神经元的形态学特征。结果显示，本研究所建立的分类模型能够通过锥体神经元的形态预测其电生理特征。与mPFC中的非MD神经支配神经元相比，MD神经支配的mPFC锥体神经元表现出更大的基底树突长度，但顶端树突的复杂性更低。MD支配的mPFC锥体神经元的两种亚型(ET-1和ET-2)的形态特征不同，ET-1神经元的顶端树突比ET-2神经元更长、更复杂。本研究结果表明接受MD投射的mPFC锥体神经元的电生理特性与其形态学特征相关，提示接受MD投射的mPFC锥体神经元的两个电生理亚类在PFC局部回路以及PFC与其他皮层或皮层下脑区的环路中的作用不同。

关键词： 锥体神经元; 前额叶皮层; 背内侧丘脑; 聚类分析; 神经元重构

Electrophysiological and morphological properties of prefrontal pyramidal neurons innervated by mediodorsal thalamus

FAN Zu-Quan, TAO Xiao-Dong, WEI Ya-Ru, ZHANG Xue-Han^*

State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China

Abstract

The high-order cognitive and executive functions are necessary for an individual to survive. The densely bidirectional innervations between the medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) play a vital role in regulating high-order functions. Pyramidal neurons in mPFC have been classified into several subclasses according to their morphological and electrophysiological properties, but the properties of the input-specific pyramidal neurons in mPFC remain poorly understood. The present study aimed to profile the morphological and electrophysiological properties of mPFC pyramidal neurons innervated by MD. In the past, the studies for characterizing the morphological and electrophysiological properties of neurons mainly relied on the electrophysiological recording of a large number of neurons and their morphologic reconstructions. But, it is a low efficient method for characterizing the circuit-specific neurons. The present study combined the advantages of traditional morphological and electrophysiological methods with machine learning to address the shortcomings of the past method, to establish a classification model for the morphological and electrophysiological properties of mPFC pyramidal neurons, and to achieve more accurate and efficient identification of the properties from a small size sample of neurons. We labeled MD-innervated pyramidal neurons of mPFC using the trans-synaptic neural circuitry tracing method and obtained their morphological properties using whole-cell patch-clamp recording and morphologic reconstructions. The results showed that the classification model established in the present study could predict the electrophysiological properties of MD-innervated pyramidal neurons based on their morphology. MD-innervated pyramidal neurons exhibit larger basal dendritic length but lower apical dendrite complexity compared to non-MD-innervated neurons in the mPFC. The morphological characteristics of the two subtypes (ET-1 and ET-2) of mPFC pyramidal neurons innervated by MD are different, with the apical dendrites of ET-1 neurons being longer and more complex than those of ET-2 neurons. These results suggest that the electrophysiological properties of MD- innervated pyramidal neurons within mPFC correlate with their morphological properties, indicating that the different roles of these two subclasses in local circuits within PFC, as well as in PFC-cortical/subcortical brain region circuits.

Key words: Pyramidal neurons; prefrontal cortex; mediodorsal thalamus; cluster analysis; neuronal reconstruction

收稿日期：　　录用日期：

通讯作者：张雪寒　　E-mail: xuehanzhang@fudan.edu.cn

DOI: 10.13294/j.aps.2023.0074

引用本文：

范祖权, 陶晓冬, 魏亚茹, 张雪寒. 接受背内侧丘脑投射的前额叶皮层锥体神经元的电生理学和形态学特性(英文)[J]. 生理学报 2024; 76 (2): 233-246.

FAN Zu-Quan, TAO Xiao-Dong, WEI Ya-Ru, ZHANG Xue-Han. Electrophysiological and morphological properties of prefrontal pyramidal neurons innervated by mediodorsal thalamus. Acta Physiol Sin 2024; 76 (2): 233-246