中文摘要:
GABA能中间神经元被认为通过在不同的锥体细胞群上建立非选择性连接来调节兴奋性网络,但最近的研究表明存在细胞类型特异性抑制性连接组。中间神经元如何以及何时在混合的兴奋性神经元群之间建立精确的连接模式仍然是一个谜。我们探索了小鼠大脑皮层中细胞类型特异性抑制出现的分子机制。我们证明,第 5 层内 (L5 IT) 和端脑外 (L5 ET) 神经元表达特定的转录程序,使它们能够塑造小白蛋白 (PV) 和胆囊收缩素阳性 (CCK) 中间神经元线路。我们确定了 Cdh12 和 Cdh13 这两个钙粘蛋白超家族成员,作为 L5 锥体细胞群细胞类型和输入特异性抑制模式的基础。多重单突触追踪揭示了 IT 和 ET 突触前抑制网络之间的重叠极小,并表明不同的 PV 篮子细胞群支配不同的 L5 锥体细胞类型。在这里,我们揭示了钙粘蛋白在塑造细胞类型特异性皮质中间神经元布线中的贡献。
英文摘要:
GABAergic interneurons were thought to regulate excitatory networks by establishing unselective connections onto diverse pyramidal cell populations, but recent studies demonstrate the existence of a cell type-specific inhibitory connectome. How and when interneurons establish precise connectivity patterns among intermingled populations of excitatory neurons remains enigmatic. We explore the molecular mechanisms orchestrating the emergence of cell type-specific inhibition in the mouse cerebral cortex. We demonstrate that layer 5 intra- (L5 IT) and extra-telencephalic (L5 ET) neurons express unique transcriptional programs, allowing them to shape parvalbumin- (PV+) and cholecystokinin-positive (CCK+) interneuron wiring. We identified Cdh12 and Cdh13, two cadherin superfamily members, as underpinnings of cell type- and input-specific inhibitory patterns of L5 pyramidal cell populations. Multiplex monosynaptic tracing revealed a minimal overlap between IT and ET presynaptic inhibitory networks and suggests that different PV+ basket cell populations innervate distinct L5 pyramidal cell types. Here, we unravel the contribution of cadherins in shaping cell-type-specific cortical interneuron wiring.
论文信息:
论文题目:Cadherins orchestrate specific patterns of perisomatic inhibition onto distinct pyramidal cell populations
期刊名称:Nature Communications
时间期卷:16, Article number: 4481 (2025)
在线时间:2025年5月14日
DOI:doi.org/10.1038/s41467-025-59635-z
产品信息:
货号:R-180, G-180
规格:100ul
品牌:Lumafluor
产地:美国
名称:Fluorescent Retrobeads IX
办事处:Target Technology(靶点科技)
Lumafluor对于可靠,稳健的逆行运输,只有一个选择:来自Lumafluor的RetroBeads™。来自Lumafluor的RetroBeads™-用于逆行追踪的微球,以及在实验中证明有效的无替代微球:绿色和红色荧光RetroBeads™仅由Lumafluor提供。高度限制的注射-非常适合详细的连接性研究。活细胞无限期(1年!),无毒。与大多数其他顺行示踪剂,原位杂交和免疫组织化学兼容。Retrobeads™IX:Retrobeads™向局部区域提供生物活性剂(如神经营养因子和神经递质激动剂/拮抗剂);逆行运输允许确定哪些神经元暴露于药剂[Riddle等。Nature378:189,1995和Quattrochi等。Science245:984,1989]。Retrobeads™IX专门用于促进蛋白质和其他生物活性化合物的吸附。与标准的Retrobeads™相比,Retrobeads™IX在灵长类动物系统中也是更有效的示踪剂。美国Lumafluor逆向示踪荧光微球Fluorescent Retrobeads IX见刊于Nature Communications:钙粘蛋白将特定的围体抑制模式编排到不同的锥体细胞群上
Lumafluor逆向示踪荧光微球Fluorescent Retrobeads IX的材料和方法:
L5 pyramidal cell populations were targeted using green (488 nm) or red (555 nm) fluorescent retrobeads IX (Lumafluor Corp., FL). P2-3 pups were anesthetized with isoflurane (2.5%) and mounted on a stereotactic frame using a 3D printed isoflurane mask. Unilateral injections of 75 nl retrobeads at 30 nl/min were carried out as follows: L5 IT were labeled by targeting the contralateral somatosensory cortex (S1) (AP + 1.6, ML −1.9 to −2.2, DV −0.8 to −0.5), L5 ET were labeled by targeting the Pons (AP −0.3, ML + 0.3, DV −4.5 to −4.0). Retrobeads were sonicated prior to each injection to avoid aggregate formation. The pipette was retracted from the brain after 2 min to allow for diffusion.
材料和方法文献截图: