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FUNCTION OF GLUTAMATE RECEPTORS IN VISUAL CORTEX

视觉皮层谷氨酸受体的功能

基本信息

批准号：
6524922
负责人：
NIGEL W DAW
金额：
$ 24.53万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-05-01 至 2004-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6524922
关键词：
NMDA receptors action potentials age difference brain mapping calcium flux cell type developmental neurobiology electrophysiology glutamate receptor laboratory rat long term potentiation neural plasticity neural transmission neurophysiology phosphatidylinositols protein kinase A receptor expression visual cortex

项目摘要

DESCRIPTION (Adapted from applicant's abstract): Plasticity in the visual cortex is demonstrated in the whole animal by ocular dominance shifts that occur after monocular deprivation. It can also be demonstrated in the form of long-term potentiation (LTP) and long-term depression (LTD). Even though ocular dominance plasticity takes days to occur, and involves anatomical changes, and LTP and LTD are physiological changes produced in minutes, the initial steps in both forms of plasticity are same. For example, both depend in part on the activation of NMDA receptors.These initial steps can be studied with LTP and LTD much more quickly than they can be studied in the intact animal. Moreover, using whole cell recordings, one can study intracortical plasticity and distinguish presynaptic mechanisms from postsynaptic mechanisms, both of which are difficult to do in the intact animal. Both ocular dominance plasticity and LTP have a critical period that varies with age and layer in the visual cortex. We will pursue the hypothesis that there are different mechanisms in different layers and maybe at different ages that account for these variations. NMDA receptors and metabotropic glutamate receptors are both known to be involved in plasticity. Based on our previous work, we suggest that NMDA receptors are important late in the critical period in the upper layers II and III, but not in the lower layers V and VI. Based on our current work, we suggest that Group I metabotropic glutamate receptors play a potentiating role in lower layers, while Group II metabotropic glutamate receptors play a depressive role in upper layers. The second messenger cAMP is increased by metabotropic glutamate receptors by a quantity that is closely related to the critical period. We therefore also suggest that cAMP plays a long-term potentiating role, and based on our current work, that cGMP plays a depressive role.

描述（改编自申请人的摘要）：视觉上的可塑性皮层在整个动物中通过眼优势转移得到证明发生在单眼剥夺后。也可以通过以下形式表现出来长时程增强（LTP）和长时程抑制（LTD）。尽管眼优势可塑性需要几天的时间才能发生，并且涉及解剖学的变化，并且 LTP 和 LTD 是在几分钟内产生的生理变化，是两种形式的可塑性是相同的。例如，两者都部分取决于 NMDA 受体的激活。这些初始步骤可以用 LTP 和限制的速度比在完整动物中研究它们的速度要快得多。而且，利用全细胞记录，人们可以研究皮质内可塑性和区分突触前机制和突触后机制，两者在完整的动物身上很难做到。眼部优势可塑性和 LTP有一个关键期，该期随年龄和视觉层次的不同而变化皮质。我们将追求以下假设：存在不同的机制不同的层次，可能是不同的年龄，导致了这些差异。 NMDA 受体和代谢型谷氨酸受体均已知涉及可塑性。根据我们之前的工作，我们建议 NMDA 受体在上层II和关键期的后期很重要 III，但不在下层 V 和 VI 中。根据我们目前的工作，我们表明 I 类代谢型谷氨酸受体发挥增强作用在下层，而 II 类代谢型谷氨酸受体则发挥着上层的抑制作用。第二信使 cAMP 增加代谢型谷氨酸受体的数量与关键时期。因此，我们还建议 cAMP 发挥长期作用增强作用，并且根据我们目前的工作，cGMP 具有抑制作用角色。