Long-Term Depression in Aplysia sensorimotor synapses

海兔感觉运动突触的长期抑制

• 批准号: 6769533
• 负责人: GREGORY J VILLAREAL
• 金额: $ 2.98万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6769533
• 关键词: AMPA receptors; Aplysia; NMDA receptors; calcium; glutamate receptor; learning; neural plasticity; phosphoprotein phosphatase; predoctoral investigator; receptor expression; receptor mediated endocytosis; synapses; tissue /cell culture

DESCRIPTION (provided by applicant): The main objective of the grant proposal will be to determine the mechanisms that underlie homosynaptic long-term depression (LTD) in Aplysia californica sensorimotor synapses in culture. LTD is a form of synaptic plasticity that is thought to represent a cellular correlate for mammalian learning and memory. Although it is believed to underlie learning, LTD remains inconclusive regarding a behavioral role in learning. Our laboratory believes that LTD can underlie long-term habituation a simple learning behavior that has been well defined and studied in Aplysia. Thus, determining mechanisms of LTD in culture will lend insight into the behavior of the animal. Previous work from our lab has shown that LTD of Aplysia sensorimotor synapses requires a postsynaptic rise in intracellular calcium. Experiments will test if the rise in calcium is mediated by activation of postsynaptic N-methyl-D-aspartate (NMDA) receptors. Experiments will also test for other possible targets such as metabotropic glutamate receptors, L-Type calcium channels or intracellular calcium store activation. Furthermore, the proposed project will test for the role of protein phosphatase activation and the role of AMPA receptor endocytosis in the induction of LTD at Aplysia sensorimotor synapses in culture. Ultimately, the results from the project will increase our knowledge on the cellular correlates of synaptic plasticity in the Aplysia central nervous system while contributing to the general understanding of human related diseases such as Alzheimers and other related human-learning deficits.

描述（由申请人提供）：该资助提案的主要目标是确定培养的加州阿氏藻感觉运动突触中同源突触长期抑制（LTD）的机制。LTD是突触可塑性的一种形式，被认为代表了哺乳动物学习和记忆的细胞相关性。虽然它被认为是学习的基础，但LTD在学习中的行为作用方面仍然没有定论。我们的实验室认为，LTD可以作为长期习惯化的基础，这是一种简单的学习行为，在Arachsia已经得到了很好的定义和研究。因此，确定LTD在文化中的机制将有助于深入了解动物的行为。我们实验室以前的工作表明，LTD的感觉运动突触需要突触后细胞内钙离子的上升。实验将测试钙的升高是否由突触后N-甲基-D-天冬氨酸（NMDA）受体的激活介导。实验还将测试其他可能的靶点，如代谢型谷氨酸受体、L型钙通道或细胞内钙储存激活。此外，拟议的项目将测试蛋白磷酸酶激活的作用和AMPA受体内吞作用在培养的海兔感觉运动突触诱导LTD中的作用。最终，该项目的结果将增加我们对失智症中枢神经系统中突触可塑性的细胞相关性的了解，同时有助于对人类相关疾病（如阿尔茨海默氏症和其他相关人类学习缺陷）的普遍理解。