Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Front Neural Circuits. 2021 Sep 24;15:728832. doi: 10.3389/fncir.2021.728832. eCollection 2021.
The cerebral cortex contains numerous neuronal cell types, distinguished by their molecular identity as well as their electrophysiological and morphological properties. Cortical function is reliant on stereotyped patterns of synaptic connectivity and synaptic function among these neuron types, but how these patterns are established during development remains poorly understood. Selective targeting not only of different cell types but also of distinct postsynaptic neuronal domains occurs in many brain circuits and is directed by multiple mechanisms. These mechanisms include the regulation of axonal and dendritic guidance and fine-scale morphogenesis of pre- and postsynaptic processes, lineage relationships, activity dependent mechanisms and intercellular molecular determinants such as transmembrane and secreted molecules, many of which have also been implicated in neurodevelopmental disorders. However, many studies of synaptic targeting have focused on circuits in which neuronal processes target different lamina, such that cell-type-biased connectivity may be confounded with mechanisms of laminar specificity. In the cerebral cortex, each cortical layer contains cell bodies and processes from intermingled neuronal cell types, an arrangement that presents a challenge for the development of target-selective synapse formation. Here, we address progress and future directions in the study of cell-type-biased synaptic targeting in the cerebral cortex. We highlight challenges to identifying developmental mechanisms generating stereotyped patterns of intracortical connectivity, recent developments in uncovering the determinants of synaptic target selection during cortical synapse formation, and current gaps in the understanding of cortical synapse specificity.
大脑皮层包含众多神经元细胞类型，这些细胞类型在分子特征、电生理特性和形态特征上存在差异。皮层功能依赖于这些神经元类型之间的突触连接和突触功能的刻板模式，但这些模式在发育过程中是如何建立的仍知之甚少。在许多脑回路中，不仅不同的细胞类型，而且不同的突触后神经元区域都存在选择性靶向，这是由多种机制指导的。这些机制包括轴突和树突导向的调节以及前后突触过程的精细形态发生、谱系关系、依赖于活动的机制以及细胞间分子决定因素，如跨膜和分泌分子，其中许多分子也与神经发育障碍有关。然而，许多关于突触靶向的研究都集中在神经元过程靶向不同层的回路中，因此细胞类型偏向性连接可能与层特异性机制混淆。在大脑皮层中，每个皮层层都包含来自混合神经元细胞类型的胞体和过程，这种排列对目标选择性突触形成的发育提出了挑战。在这里，我们探讨了大脑皮层中细胞类型偏向性突触靶向研究的进展和未来方向。我们强调了确定产生皮质内连接刻板模式的发育机制的挑战、揭示皮质突触形成过程中突触靶向选择决定因素的最新进展，以及对皮质突触特异性理解的当前差距。
