Constitutively active group I mGlu receptors and PKMzeta regulate synaptic transmission in developing perirhinal cortex.
Constitutively active group I mGlu receptors and PKMzeta regulate synaptic transmission in developing perirhinal cortex.
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DOI：
10.1016/j.neuropharm.2012.03.010
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发表时间：
2013-03
影响因子：
4.7
通讯作者：
Bashir ZI
中科院分区：
文献类型：
--
作者：
Panaccione I;King R;Molinaro G;Riozzi B;Battaglia G;Nicoletti F;Bashir ZI
突触传递对中枢神经系统的早期发育至关重要。然而，调节大脑皮层早期突触传递的机制尚不清楚。PKMζ是维持LTP所必需的激酶。我们首次表明，PKMζ的抑制产生的基础突触传递的新生儿，而不是成年，大鼠周围皮层深刻的抑制。这表明早期发育的突触处于一种类似ltp的结构状态。此外，在未成熟但未成熟的鼻周皮质中，基础突触传递依赖于代谢性谷氨酸（mGlu）受体、PI3Kinase和哺乳动物雷帕霉素靶点（mTOR）的持续活性。因此，在发育早期，皮质突触以ltp样状态存在，由强直活性的mGlu受体、mTOR和PKMζ依赖级联维持。这些结果对发育过程中控制突触的分子机制提供了新的认识，并可能有助于我们对自闭症和精神分裂症等发育障碍的理解。
Synaptic transmission is essential for early development of the central nervous system. However, the mechanisms that regulate early synaptic transmission in the cerebral cortex are unclear. PKMζ is a kinase essential for the maintenance of LTP. We show for the first time that inhibition of PKMζ produces a profound depression of basal synaptic transmission in neonatal, but not adult, rat perirhinal cortex. This suggests that synapses in early development are in a constitutive LTP-like state. Furthermore, basal synaptic transmission in immature, but not mature, perirhinal cortex relies on persistent activity of metabotropic glutamate (mGlu) receptor, PI3Kinase and mammalian target of rapamycin (mTOR). Thus early in development, cortical synapses exist in an LTP-like state maintained by tonically active mGlu receptor-, mTOR- and PKMζ- dependent cascades. These results provide new understanding of the molecular mechanisms that control synapses during development and may aid our understanding of developmental disorders such as autism and schizophrenia.
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