SYNAPSES AS INFORMATION PROCESSING & MEMORY ELEMENTS

突触作为信息处理

基本信息

批准号：
3396286
负责人：
WILLIAM B LEVY
金额：
$ 15.09万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
1979
资助国家：
美国
起止时间：
1979-07-01 至 1993-08-31
项目状态：
已结题

项目摘要

It has always been expected that understanding normal brain function, particularly the cellular bases of learning and memory, would lead to clinically relevant results, but no one dared guess how quickly this relevance would arrive. A hypothesis held by several researchers is that brain pathologies resulting from ischemia and anoxia develop because of excessive neural activity. It is not just activity, however, but activity that activates NMDA receptors. The activation of NMDA receptors requires associative activity of the very type we are studying. That is, the NMDA receptors are not there to kill cells but are there to mediate associative learning. The proposed research continues our NIH- funded research and uses anatomy, physiology, and biophysical modeling to extend our knowledge of long-term associative synaptic modification. The extension goes in two directions: one extension is to another synaptic system; the other extension is to relate long-term associative potentiation to induced brain pathologies. The other synaptic system is formed by entorhinal cortical (EC) afferents on the spiny pyramids of hippocampal CAl. Associative potentiation at these synapses is of interest in its own right but has an additional importance. The CAl pyramids represent a sensible transition which should allow a bridging of knowledge gained from the dentate granule cells to the pyramids of cerebral cortex. That is, the distal spine synapses of CAl are quite similar to the EC-DG synapses we have studied and to the layer-l spine synapses of cerebral cortex. In CAl we will study two types of changes: a homogeneous associative potentiation of the bilateral EC projections to the CAl molecular layer, and a heterogenous interaction in which the EC-CAl synapses generate the permissive event for CA3-CAl synaptic modification. The research will evaluate both the ultrastructural and physiological characteristics of these changes. Biophysical models will examine the implications of the morphological alterations for cellular spatiotemporal integration and the rules of LTP. By correlating the ultrastructural characteristics of LTP with the ultrastructural characteristics of epilepsy and of ischemic/traumatic brain injury, we will examine the relationship between associative modification and the relevant class of brain methodologies. The question is: to what extent is LTP a correlate of these pathologies? Key observations will be any ultrastructural correlates shared by LTP and these pathologies. LTP-like changes may be a transitional state before ischemic cell death while the epileptic state may require LTP.

人们一直期望了解正常的大脑功能，特别是学习和记忆的细胞基础，会导致临床相关的结果，但没人敢猜测这种相关性多久就会出现。持有的一个假设一些研究人员认为，大脑病变是由由于过度的神经活动而导致缺血和缺氧。然而，激活 NMDA 的不仅仅是活动受体。 NMDA 受体的激活需要结合正是我们正在研究的那种活动。也就是说，国家药品监督管理局受体不是用来杀死细胞的，而是用来介导的联想学习。拟议的研究继续我们的 NIH- 资助研究并使用解剖学、生理学和生物物理学建模以扩展我们对长期关联突触的了解修改。延伸有两个方向：一个延伸是另一个突触系统；另一个扩展是关联诱发大脑病理的长期联想增强。另一个突触系统由内嗅皮质（EC）形成海马 CA1 多刺金字塔上的传入。联想式这些突触的增强作用本身就很有趣，但是还有一个额外的重要性。 CAl 金字塔代表合理的过渡应该能够架起知识的桥梁从齿状颗粒细胞获得到大脑金字塔皮质。也就是说，CA1 的远端棘突触相当类似于我们研究过的 EC-DG 突触和 l 层大脑皮层的棘突触。在CAl中我们将研究两种类型变化：双边的同质联想增强 EC 投影到 CA1 分子层，以及异质 EC-CAl突触产生许可性的相互作用 CA3-CA1突触修饰的事件。该研究将评估超微结构和生理特征这些变化。生物物理模型将研究其影响细胞时空形态变化集成和 LTP 规则。通过关联 LTP 的超微结构特征癫痫和缺血性/创伤性脑损伤的特征，我们将研究联想修饰之间的关系以及相关的大脑方法论类别。问题是： LTP 在多大程度上与这些病理相关？钥匙观察结果将是 LTP 共享的任何超微结构相关性和这些病症。类似 LTP 的变化可能是过渡性的缺血性细胞死亡前的状态，而癫痫状态可能需要 LTP。