Glutamate induces de novo growth of functional spines in developing cortex.
Glutamate induces de novo growth of functional spines in developing cortex.
复制标题
DOI：
10.1038/nature09986
复制
发表时间：
2011-06-02
期刊：
影响因子：
64.8
通讯作者：
Sabatini, Bernardo L.
中科院分区：
文献类型：
--
作者：
Kwon, Hyung-Bae;Sabatini, Bernardo L.
成熟的皮质锥体神经元接受来自其树突(称为棘突)的小突起的兴奋性输入。脊椎在发育过程中经历依赖活动的重塑、稳定和修剪，类似的结构变化可以由学习和感官体验的变化触发。然而，在发育中的大脑中，新的脊椎形成的生化触发和机制以及新的脊椎对神经元连接的功能意义在很大程度上是未知的。我们开发了一种方法，利用双光子激光扫描显微镜和双光子激光对谷氨酸的浸泡，实时诱导和监测新生脊柱的形成。我们的数据表明，在小鼠皮质第2/3层锥体神经元中，谷氨酸足以以一种特定位置的方式从树突干触发从头开始的脊椎生长。我们发现，谷氨酸诱导的脊髓发生需要NMDA型谷氨酸受体的开放和PKA的激活，但不依赖CaMKII和TrkB受体。此外，新形成的脊椎表达谷氨酸受体，并具有快速功能，将突触前活动转化为突触后信号。总而言之，我们的数据表明，早期神经连接是由空间精确方式的活动塑造的，新生的树突刺在功能上迅速整合到皮质回路中。
Mature cortical pyramidal neurons receive excitatory inputs onto small protrusions emanating from their dendrites called spines. Spines undergo activity-dependent remodeling, stabilization, and pruning during development and similar structural changes can be triggered by learning and changes in sensory experiences. However, the biochemical triggers and mechanisms of de novo spine formation in the developing brain and the functional significance of new spines to neuronal connectivity are largely unknown. We developed an approach to induce and monitor de novo spine formation in real-time using combined two-photon laser-scanning microscopy and two-photon laser uncaging of glutamate. Our data demonstrate that, in mouse cortical layer 2/3 pyramidal neurons, glutamate is sufficient to trigger de novo spine growth from the dendrite shaft in a location-specific manner. We find that glutamate-induced spinogenesis requires opening of NMDA-type glutamate receptors and activation of PKA but is independent of CaMKII and TrkB receptors. Furthermore, newly formed spines express glutamate receptors and are rapidly functional such that they transduce presynaptic activity into postsynaptic signals. Together, our data demonstrate that early neural connectivity is shaped by activity in a spatially precise manner and that nascent dendrite spines are rapidly functionally incorporated into cortical circuits.
登录
查看更多内容
影响因子：
64.8
作者：
Engert, F;Bonhoeffer, T
通讯作者：
Bonhoeffer, T
影响因子：
5.5
作者：
Busetto, Giuseppe;Higley, Michael J.;Sabatini, Bernardo L.
通讯作者：
Sabatini, Bernardo L.
影响因子：
2.9
作者：
HAMORI, J
通讯作者：
HAMORI, J
影响因子：
16.2
作者：
Chalifoux JR;Carter AG
通讯作者：
Carter AG
影响因子：
64.8
作者：
Matsuzaki, M;Honkura, N;Kasai, H
通讯作者：
Kasai, H