在体大鼠海马区侧枝联合纤维通路和TA通路的不同空间整合特性

在麻醉Wistar大鼠上,结合脑室给药,应用双电极刺激技术刺激海马独立的两条侧枝／联合纤维通 路、TA通路,并在CAl区放射层记录兴奋性突触后电位(EPSP),对海马CAl区锥体细胞近、远端树突EPSP 的空间整合进行了初步探讨。结果表明,海马CAl区锥体细胞近、远端树突的空间整合都是亚线性的;近端树 突的空间整合不受期望值大小的影响,但远端树突的空间整合随期望值增加而减小(更趋于亚线性)。此外, 荷包牡丹碱没有影响EPSP的空间整合;但瞬时A型钾通道(IAK+)的拮抗剂氨基吡啶-4却使得近端树突的 空间整合趋于线性发展。本研究表明,海马CAl锥体细胞近、远端树突不同的被动、主动特征使它们具有了不 同的空间整合特性。由于近端树突接受海马内部侧枝／联合纤维投射的信息,远端树突通过TA通路接受内嗅皮 层投射的信息,由此提示,CAl区锥体细胞对来自海马内部和直接来自皮层的信息输入采用了不同的整合方 式。

PLCß介导的钙调腺苷酸环化酶在突触可塑性相关基因转录中的作用和FE65对海马依赖学习及LTP的调节

Gene regulation is required for activity-dependent changes in synaptic plasticity and remodeling. The metabotropic glutamate receptors (mGluRs) contribute to different brain functions, including learning/memory, mental disorders, drug addiction, and persistent pain in the CNS. We found that Gp I mGluRs activate PLCß through Gq and then lead to activation of several calcium-dependent signaling pathways, including ERK, which play an important role in gene transcription. These findings support a calcium-dependent role for Gq in release of Calcium and activation of calcium-stimulated adenylyl cyclases I in activity-dependent transcription in response to application of group I metabotropic glutamate receptors agonist and may provide insights into group I mGluRs-dependent synaptic plasticity through MAP kinases signaling. Moreover, the present study investigated the transcription-dependent changes of Arc in response to the activation of group I mGluRs and suggested the central role of ERK1/2 in group I mGluR-mediated Arc transcription. Further, we selected APP-interaction protein FE65 to investigate the mechanism of transcription-related process in synaptic plasticity. FE65 is expressed predominantly in the brain, and interacts with the C-terminal domain of β-amyloid precursor protein (APP). We examined hippocampus-dependent memory and in vivo long-term potentiation (LTP) at the CA1 synapses with the isoform-specific FE65 knock-out (p97FE65-/-) mice. p97FE65 knock-out mice showed impaired short-term memory for both TDPA and CFC when tested 10min after training, which is transcription-independent. Consistently, at the Schaffer collateral-CA1 synapses, p97FE65 knock-out mice showed defective early phase LTP. These results demonstrate novel roles of FE65 in synaptic plasticity, acquisition, and retention for certain forms of memory formation.