CELLULAR MECHANISM OF HIPPOCAMPAL LONG-TERM POTENTIATION

海马长时程增强的细胞机制

基本信息

批准号：
2264962
负责人：
JOHN M SARVEY
金额：
$ 15.67万
依托单位：
HENRY M. JACKSON FDN FOR THE ADV MIL/MED
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-04-01 至 2000-12-31
项目状态：
已结题

项目摘要

Long-term potentiation (LTP) is an example of activity-dependent plasticity, which has been studied intensively in the hippocampal formation. In the dentate gyrus, beta-adrenergic agonist-induced long- lasting potentiation (BAALLP) bears strong similarities to LTP. In particular, both require activation of N-methyl-D-aspartate (NMDA) receptors. The objective of the proposed research is to test the hypothesis that, at the medial perforant path-granule cell synapse, (1) LTP requires activation of the NMDA and metabotropic (ACPD) excitatory amino acid (EAA) receptors, and (2) beta-adrenergic agonists activate the NMDA receptor and either activate or circumvent the ACPD receptor to initiate the same events as those underlying LTP. Experiments at the medial perforant path-granule cell synapse of rat hippocampal slice are planned to determine: 1. The role of NMDA and ACPD receptors in LTP and BAALLP. Patch clamp, intracellular, and extracellular recording will be used to determine the roles of beta-adrenergic receptors and GABA-mediated inhibition in LTP and BAALLP, the ability of NMDA and ACPD, alone and in combination, to induce an LLP, and whether LTP and/or BAALLP results from increased release of EAA transmitter or increased postsynaptic sensitivity to EAA. 2. The role of second messengers and protein kinases in production and maintenance of LTP and BAALLP. Granule cells will be perfused internally with patch or intracellular pipets containing calcium chelators, cAMP analogs, or IP3. Effects of PKC activators, such as phobol esters, and PKC antagonists will be evaluated by electrophysiological and biochemical methods. Internal perfusion of cAMP- dependent protein kinase or PKC may give some insight into possible final common pathways for these two kinases. 3. The role of G proteins in the production and maintenance of LTP and BAALLP. Internal perfusion of granule cells with patch of intracellular pipets containing GTPgammaS or GDPbetaS will indicate whether (a) postsynaptic G protein(s) are required for LTP and BAALLP. Injection of purified G proteins and subunits into granule cells will be attempted in order to determine which G protein(s) is/are involved in LTP and BAALLP. The long-term goal of this research is to clarify the relationship between LTP and BAALLP, and thereby increase understanding of mechanisms of synaptic plasticity and cellular information storage.

长期增强（LTP）是活动依赖性的一个例子可塑性，在海马中进行了深入研究形成。在齿状回中，β-肾上腺素能激动剂诱导的长长持久的增强（Baallp）与LTP具有很强的相似性。在特别是，两者都需要激活N-甲基-D-天冬氨酸（NMDA）受体。拟议研究的目的是测试假设，在内侧穿孔路径颗粒细胞突触中，（1）LTP 需要激活NMDA和代谢性（ACPD）兴奋性氨基酸（EAA）受体，（2）β-肾上腺素能激动剂激活NMDA 受体并激活或绕过ACPD受体启动与基础LTP的事件相同。大鼠内侧穿孔式颗粒细胞突触的实验计划确定海马切片：1。NMDA和ACPD的作用 LTP和BAALLP中的受体。斑块夹，细胞内和细胞外记录将用于确定β-肾上腺素能受体的作用 LTP和BAALLP中GABA介导的抑制作用，NMDA和 ACPD，单独和组合诱导LLP，以及LTP和/或 BAALLP导致EAA发射器的释放增加或增加突触后对EAA的敏感性。 2。第二使者和 LTP和BAALLP生产和维持中的蛋白激酶。颗粒细胞将用斑块或细胞内移液器内部灌注包含钙螯合剂，营地类似物或IP3。 PKC的影响激活剂，例如phobol酯和PKC拮抗剂将通过电生理和生化方法。营地的内部灌注 - 依赖性蛋白激酶或PKC可能会深入了解可能的最终这两个激酶的常见途径。 3。G蛋白在 LTP和BAALLP的生产和维护。内部灌注带有含有GTPGAMMAS或 GDPBETAS将指示（a）突触后G蛋白是否需要用于LTP和Baallp。将纯化的G蛋白和亚基注入将尝试尝试颗粒细胞以确定哪种G蛋白 IS/参与LTP和BAALLP。这项研究的长期目标是阐明 LTP和Baallp，从而增加了对机制的理解突触可塑性和蜂窝信息存储。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Endogenous activation of mu and delta-1 opioid receptors is required for long-term potentiation induction in the lateral perforant path: dependence on GABAergic inhibition.

mu 和 delta-1 阿片受体的内源性激活是侧穿路径中长期增强诱导所必需的：依赖于 GABA 能抑制。

DOI：
10.1523/jneurosci.16-24-08123.1996
发表时间：
1996
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience.
影响因子：
0
作者：
Bramham,CR;Sarvey,JM
通讯作者：
Sarvey,JM

beta-NAAG rescues LTP from blockade by NAAG in rat dentate gyrus via the type 3 metabotropic glutamate receptor.

β-NAAG 通过 3 型代谢型谷氨酸受体将大鼠齿状回中的 LTP 从 NAAG 的阻断中解救出来。