张生家

邮箱： sheng-jia.zhang@biomed.tsinghua.edu.cn

 

研究方向：

2014年诺贝尔生理学或医学奖不仅肯定了发现大脑空间定位系统的多种特殊空间细胞在认知神经领域中的重要贡献，同时也为整个系统神经学提供了一个极好的研究平台，因为位置细胞、网格细胞、头方向细胞和边界细胞独特的放电模式有助于我们从基因到环路来研究大脑内置GPS的分子和细胞机制并解析与空间记忆相关的计算密码。我们将：

1.借助CRISPR/ Cas9的基因编辑平台来对海马-内嗅皮层各个亚区和各个亚层进行细胞特异性的激活和失活来研究各种空间细胞间的相关性。

2.利用神经环路特异性的光遗传学和药理遗传学来解密与空间记忆相关的计算密码。

3.对不同刺激有选择性标记的神经环路进行示踪，标记，成像，记录和计算建模。

4.将用老年痴呆症的动物模型试图修复内嗅皮层中受损的网格细胞，进行转化医学的研究。

  

代表性科研论文：

1.  Ito, HT, Zhang SJ, Witter MP, Moser EI, Moser MB. (2015). A prefrontal-thalamo-hippocampal circuit for goal-directed spatial coding. Nature in press.

2.  Zhang SJ*, Ye J*, Couey JJ, Witter MP, Moser EI, Moser MB. (2014). Functional connectivity of the entorhinal-hippocampal space circuit. Philos. Trans. R. Soc. Lond. B Bio. Sci. 369, 20120516.

3. Zhang SJ*#, Ye J*, Miao C, Tsao A, Cerniauskas I, Ledergerber D, Moser MB, Moser EI#. (2013). Optogenetic dissection of entorhinal-hippocampal functional connectivity. Science 340 (6128), 1232627 (Selected as an Enhanced 14-Page Research Article).

4.  Couey JJ*, Witoelar A*, Zhang SJ*, Zheng K, Ye, J, Dunn B, Czajkowski R, Moser, MB, Moser EI, Roudi Y, Witter MP. (2013). Recurrent inhibitory circuitry as a mechanism for grid formation. Nature Neuroscience 16, 318-324.

5.  Czajkowski R, Sugar J, Zhang SJ, Couey JJ, Ye J, Witter MP. (2013). Superficially projecting principal neurons in layer V of medial entorhinal cortex in the rat receive excitatory retrosplenial input. Journal of Neuroscience 33, 15779-15792.

6.   Zhang SJ, Buchthal B, Lau D, Hayer SN, Dick O, Schwaninger M, Veltkamp R, Zou M, Weiss U, Bading H. (2011). A signaling cascade of nuclear calcium-CREB-ATF3 activated by synaptic NMDA receptors defines a gene repression module that protects against extrasynaptic NMDA receptor-induced neuronal cell death and ischemic brain damage. Journal of Neuroscience 31, 4978-4990.

7.  Zhang SJ, Zou M, Lu L, Lau D, Ditzel DAW, Delucinge-Vivier C, Aso Y, Descombes P, Bading H. (2009). Nuclear calcium signaling controls expression of a large gene pool: identification of a gene program for acquired neuroprotection induced by synaptic activity. PLoS Genetics 5(8), e1000604.

8.  Zhang SJ, Steijaert MN, Lau D, Schütz G, Delucinge-Vivier C, Descombes P, Bading H. (2007). Decoding NMDA receptor signaling: identification of genomic programs specifying neuronal survival and death. Neuron 53, 549-562. 

 (*co-first/# co-corresponding):