鈣粘蛋白將特定的圍體抑制模式編排到不同的錐體細胞群上

中文摘要：

GABA能中間神經(jīng)元被認(rèn)為通過在不同的錐體細胞群上建立非選擇性連接來調(diào)節(jié)興奮性網(wǎng)絡(luò)，但最近的研究表明存在細胞類型特異性抑制性連接組。中間神經(jīng)元如何以及何時在混合的興奮性神經(jīng)元群之間建立精確的連接模式仍然是一個謎。我們探索了小鼠大腦皮層中細胞類型特異性抑制出現(xiàn)的分子機制。我們證明，第 5 層內(nèi) （L5 IT） 和端腦外 （L5 ET） 神經(jīng)元表達特定的轉(zhuǎn)錄程序，使它們能夠塑造小白蛋白 （PV） 和膽囊收縮素陽性 （CCK） 中間神經(jīng)元線路。我們確定了 Cdh12 和 Cdh13 這兩個鈣粘蛋白超家族成員，作為 L5 錐體細胞群細胞類型和輸入特異性抑制模式的基礎(chǔ)。多重單突觸追蹤揭示了 IT 和 ET 突觸前抑制網(wǎng)絡(luò)之間的重疊極小，并表明不同的 PV 籃子細胞群支配不同的 L5 錐體細胞類型。在這里，我們揭示了鈣粘蛋白在塑造細胞類型特異性皮質(zhì)中間神經(jīng)元布線中的貢獻。

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.

論文信息：

論文題目：Cadherins orchestrate specific patterns of perisomatic inhibition onto distinct pyramidal cell populations

期刊名稱：Nature Communications

時間期卷：16, Article number: 4481 (2025)

在線時間：2025年5月14日

DOI：doi.org/10.1038/s41467-025-59635-z

產(chǎn)品信息：

貨號：R-180, G-180

規(guī)格：100ul

品牌：Lumafluor

產(chǎn)地：美國

名稱：Fluorescent Retrobeads IX

辦事處：Target Technology(靶點科技)

Lumafluor對于可靠，穩(wěn)健的逆行運輸，只有一個選擇：來自Lumafluor的RetroBeads™。來自Lumafluor的RetroBeads™-用于逆行追蹤的微球，以及在實驗中證明有效的無替代微球：綠色和紅色熒光RetroBeads™僅由Lumafluor提供。高度限制的注射-非常適合詳細的連接性研究。活細胞無限期（1年！），無毒。與大多數(shù)其他順行示蹤劑，原位雜交和免疫組織化學(xué)兼容。Retrobeads™IX：Retrobeads™向局部區(qū)域提供生物活性劑（如神經(jīng)營養(yǎng)因子和神經(jīng)遞質(zhì)激動劑/拮抗劑）;逆行運輸允許確定哪些神經(jīng)元暴露于藥劑[Riddle等。Nature378：189,1995和Quattrochi等。Science245：984,1989]。Retrobeads™IX專門用于促進蛋白質(zhì)和其他生物活性化合物的吸附。與標(biāo)準(zhǔn)的Retrobeads™相比，Retrobeads™IX在靈長類動物系統(tǒng)中也是更有效的示蹤劑。美國Lumafluor逆向示蹤熒光微球Fluorescent Retrobeads IX見刊于Nature Communications：鈣粘蛋白將特定的圍體抑制模式編排到不同的錐體細胞群上

Lumafluor逆向示蹤熒光微球Fluorescent Retrobeads IX的材料和方法：

Retrobeads

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.

材料和方法文獻截圖：