Department of Biology, James Madison University, Harrisonburg, Virginia, USA.
Glia. 2022 Apr;70(4):697-711. doi: 10.1002/glia.24134. Epub 2021 Dec 28.
Microglial cells (MGCs) are highly dynamic and have been implicated in shaping discrete neural maps in several unimodal systems. MGCs respond to numerous cues in their microenvironment, including the neuronally expressed chemokine, fractalkine (CX3CL1), via interactions with its corresponding fractalkine receptor (CX3CR1). The present study examines microglial and CX3CL1 patterns with regard to the emerging modular-extramodular matrix organization within the lateral cortex of the inferior colliculus (LCIC). The LCIC is a multisensory shell region of the midbrain inferior colliculus where discrete compartments receive modality-specific connections. Somatosensory inputs terminate within modular confines, while auditory inputs target the surrounding matrix. Glutamic acid decarboxylase (GAD) is an established marker of LCIC modules in developing mouse. During early postnatal development, multimodal LCIC afferents segregate into discrete, neurochemically defined compartments. Here, we analyzed neonatal GAD67-GFP (GFP is defined as green fluorescent protein) and CX3CR1-GFP mice to assess: (1) whether MGCs are recruited to distinct LCIC compartments known to be undergoing active circuit assembly, and (2) if such behaviors are fractalkine signaling-dependent. MGCs colonize the nascent LCIC by birth and increase in density until postnatal day 12 (P12). At the peak critical period (P4-P8), MGCs conspicuously border emerging LCIC modules, prior to their subsequent invasion by P12. CX3CL1 expression becomes distinctly modular at P12, in keeping with the notion of fractalkine-mediated recruitment of microglia to modular centers. In CX3CR1 mice with compromised fractalkine signaling, microglial recruitment into modules is delayed. Taken together, these results suggest a potential role for microglia and fractalkine signaling in sculpting multisensory LCIC maps during an early critical period.
小胶质细胞（MGCs）是高度动态的，并且被认为在几个单模态系统中塑造离散的神经图谱。MGCs 对其微环境中的许多线索做出反应，包括神经元表达的趋化因子 fractalkine（CX3CL1），通过与相应的 fractalkine 受体（CX3CR1）相互作用。本研究检查了小胶质细胞和 CX3CL1 的模式，以了解中脑下丘外侧皮质（LCIC）中新兴的模块-外模块基质组织。LCIC 是中脑下丘的一个多感觉壳区，其中离散的隔室接收特定模式的连接。体感输入终止于模块范围内，而听觉输入则靶向周围的基质。谷氨酸脱羧酶（GAD）是发育中小鼠 LCIC 模块的一个既定标志物。在早期产后发育过程中，多模态 LCIC 传入神经分离成离散的、神经化学定义的隔室。在这里，我们分析了新生 GAD67-GFP（GFP 定义为绿色荧光蛋白）和 CX3CR1-GFP 小鼠，以评估：（1）MGC 是否被募集到已知正在进行主动电路组装的不同 LCIC 隔室，以及（2）这种行为是否依赖 fractalkine 信号。MGC 于出生时殖民新生 LCIC，并在出生后第 12 天（P12）之前增加密度。在关键期高峰（P4-P8），MGC 明显位于新兴 LCIC 模块的边界，然后在 P12 之前被入侵。CX3CL1 表达在 P12 时变得明显模块化，与 fractalkine 介导的小胶质细胞募集到模块中心的概念一致。在 fractalkine 信号受损的 CX3CR1 小鼠中，小胶质细胞向模块的募集被延迟。综上所述，这些结果表明小胶质细胞和 fractalkine 信号在早期关键期塑造多感觉 LCIC 图谱中可能发挥作用。
