Cre-dependent ACR2-expressing reporter mouse strain for efficient long-lasting inhibition of neuronal activity.
Cre-dependent ACR2-expressing reporter mouse strain for efficient long-lasting inhibition of neuronal activity.
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DOI：
10.1038/s41598-023-30907-2
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发表时间：
2023-03-09
影响因子：
4.6
通讯作者：
Yamanaka, Akihiro
中科院分区：
文献类型：
--
作者：
Mukai, Yasutaka;Li, Yan;Nakamura, Akiyo;Fukatsu, Noriaki;Iijima, Daisuke;Abe, Manabu;Sakimura, Kenji;Itoi, Keiichi;Yamanaka, Akihiro
光遗传学是利用高时间和空间分辨率的光照来操纵神经元活动的有力工具。阴离子通道视紫红质（ACRs）是一种光门控阴离子通道，使研究人员能够有效地抑制神经元活动。一种蓝光敏感的ACR2最近被用于几项体内研究；然而，表达ACR2的报告小鼠品系尚未报道。在这里，我们产生了一个新的报告鼠品系LSL-ACR2，其中ACR2在Cre重组酶的控制下表达。我们将该菌株与去肾上腺素能神经元特异性驱动小鼠（NAT-Cre）杂交，生成NAT-ACR2小鼠。我们通过体外免疫组织化学和电生理记录证实了ACR2在目标神经元中的cre依赖性表达和功能，并通过体内行为实验证实了其生理功能。我们的研究结果表明，LSL-ACR2小鼠品系与cre驱动小鼠品系杂交后，可以应用于光遗传抑制目标神经元，特别是持久的连续抑制。LSL-ACR2菌株可用于制备在目标神经元中均匀表达ACR2的转基因小鼠，具有穿透率高、重复性好、无组织侵袭的特点。
Optogenetics is a powerful tool for manipulating neuronal activity by light illumination with high temporal and spatial resolution. Anion-channelrhodopsins (ACRs) are light-gated anion channels that allow researchers to efficiently inhibit neuronal activity. A blue light-sensitive ACR2 has recently been used in several in vivo studies; however, the reporter mouse strain expressing ACR2 has not yet been reported. Here, we generated a new reporter mouse strain, LSL-ACR2, in which ACR2 is expressed under the control of Cre recombinase. We crossed this strain with a noradrenergic neuron-specific driver mouse (NAT-Cre) to generate NAT-ACR2 mice. We confirmed Cre-dependent expression and function of ACR2 in the targeted neurons by immunohistochemistry and electrophysiological recordings in vitro, and confirmed physiological function using an in vivo behavioral experiment. Our results show that the LSL-ACR2 mouse strain can be applied for optogenetic inhibition of targeted neurons, particularly for long-lasting continuous inhibition, upon crossing with Cre-driver mouse strains. The LSL-ACR2 strain can be used to prepare transgenic mice with homogenous expression of ACR2 in targeted neurons with a high penetration ratio, good reproducibility, and no tissue invasion.
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影响因子：
46.9
作者：
Chen R;Gore F;Nguyen QA;Ramakrishnan C;Patel S;Kim SH;Raffiee M;Kim YS;Hsueh B;Krook-Magnusson E;Soltesz I;Deisseroth K
通讯作者：
Deisseroth K
影响因子：
16.2
作者：
McCall JG;Al-Hasani R;Siuda ER;Hong DY;Norris AJ;Ford CP;Bruchas MR
通讯作者：
Bruchas MR
影响因子：
25
作者：
Mathis, Alexander;Mamidanna, Pranav;Bethge, Matthias
通讯作者：
Bethge, Matthias
影响因子：
25
作者：
Boyden, ES;Zhang, F;Deisseroth, K
通讯作者：
Deisseroth, K
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H