清华校友最新Nature文章

　　

生物通报道，来自纪念斯隆-卡特琳癌症中心发育生物学和康内尔大学医学院药理学系的研究者在Nature在线版上发布了突触研究新成果。

 

文章的通讯作者是来自纪念斯隆-卡特琳癌症研究中心的Song-Hai Shi（施松海，生物通注），他早年毕业于清华大学（1996届毕业生）生命科学与生物技术专业，曾在冷泉港Dr Roberto Malinow的实验室从事脑神经元获取和存取信息的长效增强效应。2001年，27岁的施松海因在Science上发表记忆与学习的研究而获得由Amersham Biosciences &Science颁发的年轻科学家奖，获得25000美金。

 

在Nature最新的文章中，施松海以：Specific synapses develop prederentially among sister excitatory neurons in the neocortex为题解析了大脑新皮质中姐妹兴奋性神经元（sister excitatory neurons）中特异突触优先发育的机制。

 

研究发现呈放射状的姐妹兴奋性神经元更倾向于发育单向的化学突触。此外，在成熟的大脑新皮质中，突触联合处表现出极间的方向性。

 

这些结果表明，在皮质发育过程中，来自同一克隆群的神经元更优先形成微环路，这就导致在成熟的皮质中最终发育成独立的有功能的微结构。

 

生物通推荐原文检索：Specific synapses develop preferentially among sister excitatory neurons in the neocortex

【Abstract】

Neurons in the mammalian neocortex are organized into functional columns1, 2. Within a column, highly specific synaptic connections are formed to ensure that similar physiological properties are shared by neuron ensembles spanning from the pia to the white matter. Recent studies indicate that synaptic connectivity in the neocortex is sparse and highly specific3, 4, 5, 6, 7, 8 to allow even adjacent neurons to convey information independently9, 10, 11, 12. How this fine-scale microcircuit is constructed to create a functional columnar architecture at the level of individual neurons largely remains a mystery. Here we investigate whether radial clones of excitatory neurons arising from the same mother cell in the developing neocortex serve as a substrate for the formation of this highly specific microcircuit. We labelled ontogenetic radial clones of excitatory neurons in the mouse neocortex by in utero intraventricular injection of enhanced green fluorescent protein (EGFP)-expressing retroviruses around the onset of the peak phase of neocortical neurogenesis. Multiple-electrode whole-cell recordings were performed to probe synapse formation among these EGFP-labelled sister excitatory neurons in radial clones and the adjacent non-siblings during postnatal stages. We found that radially aligned sister excitatory neurons have a propensity for developing unidirectional chemical synapses with each other rather than with neighbouring non-siblings. Moreover, these synaptic connections display the same interlaminar directional preference as those observed in the mature neocortex. These results indicate that specific microcircuits develop preferentially within ontogenetic radial clones of excitatory neurons in the developing neocortex and contribute to the emergence of functional columnar microarchitectures in the mature neocortex.

 

Song-Hai Shi的研究简介

Our primary focus is to understand the mechanisms underlying the mammalian central nervous system development. In particular, we are interested in understanding how neurons originate from the neuroepithelium and how neurons gradually yet faithfully acquire their unique and often complex morphologies and form functional circuits to fulfill their physiological roles. To approach these questions, we combine mouse genetics, in uterus embryonic manipulation, and ex vivo preparations (e.g. hippocampal dissociated neuronal culture, organotypic brain slice culture) with various assays including two-photon/confocal laser scanning microscopy imaging and electrophysiology. Currently we are working on three related topics in mammalina neuronal development and circuit formation:

 

1.  Neuronal polarity and migration

2.  Dendrite development

3.  Synapse development and plasticity

 

纪念斯隆－凯特琳癌症中心（Memorial Sloan - Kettering Cancer Center）

纪念斯隆－凯特琳癌症中心（MSKCC）是世界上历史最悠久、规模最大的私立癌症中心。最早的前身是1884年由John J. Astor夫妇等人共同建立的纽约癌症医院，最初痤落于曼哈顿上西区（Upper West Side of Manhattan）。1936年，John D. Rockefeller, Jr向医院捐赠了约克街（York Avenue）的一片土地。1939年，在这片新址建立了纪念医院（Memorial Hospital）。1940年代，通用汽车公司的两位前负责人，Alfred P. Sloan和Charles F. Kettering在纪念医院附近建立了斯隆－凯特琳研究所（Sloan-Kettering Institute，SKI）。1948年，SKI与纪念医院开始合作。1980年，正式合并成立纪念斯隆－凯特琳癌症中心。2004年，中心建立了Louis V. Gerstner, Jr.生物医学研究生院，提供癌症生物学的PhD学位教育。

 

中心目前拥有超过9000名雇员，其中包括纪念医院的717名主治医生（attending staff）和SKI的123名成员。2006年，收治21000名患者，门诊431160人。病床数425张。