A CRE/DRE dual recombinase transgenic mouse reveals synaptic zinc-mediated thalamocortical neuromodulation.
A CRE/DRE dual recombinase transgenic mouse reveals synaptic zinc-mediated thalamocortical neuromodulation.
复制标题
DOI：
10.1126/sciadv.adf3525
复制
发表时间：
2023-06-09
期刊：
影响因子：
13.6
通讯作者：
Tzounopoulos, Thanos
中科院分区：
文献类型：
--
作者：
Kouvaros, Stylianos;Bizup, Brandon;Solis, Oscar;Kumar, Manoj;Ventriglia, Emilya;Curry, Fallon P.;Michaelides, Michael;Tzounopoulos, Thanos
突触锌是一种影响突触传递和感觉加工的神经调质。突触锌的维持依赖于囊泡锌转运体ZnT 3。因此，ZnT 3基因敲除小鼠已成为研究突触锌的机制和功能的关键工具。然而，这种组成型基因敲除小鼠的使用具有显著的局限性，包括发育、代偿以及脑和细胞类型特异性问题。为了克服这些局限性，我们开发和表征了双重组酶转基因小鼠，其结合了Cre和Dre重组酶系统。这种小鼠允许他莫昔芬诱导的Cre依赖性外源基因表达或敲除ZnT 3表达神经元中的floxed基因，以及成年小鼠中的DreO依赖性区域和细胞类型特异性条件性ZnT 3敲除。使用这个系统，我们揭示了一种神经调节机制，即从丘脑神经元锌释放调节N-甲基-D-天冬氨酸受体活性在第5层锥体束神经元，揭露以前未知的功能皮质神经调节。来自丘脑神经元的突触锌调节皮质神经元中的NMDA受体活性。
Synaptic zinc is a neuromodulator that shapes synaptic transmission and sensory processing. The maintenance of synaptic zinc is dependent on the vesicular zinc transporter, ZnT3. Hence, the ZnT3 knockout mouse has been a key tool for studying the mechanisms and functions of synaptic zinc. However, the use of this constitutive knockout mouse has notable limitations, including developmental, compensatory, and brain and cell type specificity issues. To overcome these limitations, we developed and characterized a dual recombinase transgenic mouse, which combines the Cre and Dre recombinase systems. This mouse allows for tamoxifen-inducible Cre-dependent expression of exogenous genes or knockout of floxed genes in ZnT3-expressing neurons and DreO-dependent region and cell type–specific conditional ZnT3 knockout in adult mice. Using this system, we reveal a neuromodulatory mechanism whereby zinc release from thalamic neurons modulates N-methyl-d-aspartate receptor activity in layer 5 pyramidal tract neurons, unmasking previously unknown features of cortical neuromodulation. Synaptic zinc from thalamic neurons modulates NMDA receptor activity in cortical neurons.
登录
查看更多内容
影响因子：
8.2
作者：
Froemke, Robert C.;Jones, Bianca J.
通讯作者：
Jones, Bianca J.
DOI：
10.1073/pnas.1512296112
发表时间：
2015-12-22
影响因子：
11.1
作者：
Kalappa, Bopanna I.;Anderson, Charles T.;Tzounopoulos, Thanos
通讯作者：
Tzounopoulos, Thanos
影响因子：
3.7
作者：
Kouvaros, Stylianos;Kumar, Manoj;Tzounopoulos, Thanos
通讯作者：
Tzounopoulos, Thanos
影响因子：
2.5
作者：
Brown, CE;Dyck, RH
通讯作者：
Dyck, RH
影响因子：
5.3
作者：
Cody, Patrick A.;Tzounopoulos, Thanos
通讯作者：
Tzounopoulos, Thanos