Synapse-type-specific plasticity in neocortical microcircuits

新皮质微电路中突触类型特异性可塑性

• 批准号: RGPIN-2017-04730
• 负责人: Sjostrom, PerJesper
• 金额: $ 5.03万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711179
• 关键词: Synapse; type; specific; plasticity; neocortical

Neuroscientists believe that learning and memory as well as the refinement of neuronal circuits during development are due to changes in synaptic connections among interconnected neurons, known as synaptic plasticity. My team investigates plasticity in neocortex, with a focus on the more recently discovered Spike-Timing-Dependent Plasticity (STDP) paradigm, because of its excellent experimental control and biological plausibility. With classical STDP, pre before postsynaptic firing within a few milliseconds results in strengthening, whereas the opposite temporal order elicits weakening, which effectively enables the brain to learn causal relationships. But synaptic plasticity is known to vary with synapse type -- different mechanisms and phenomenology are found at inputs to different interneuronal classes. Why and how does synaptic plasticity vary? In this Discovery Grant proposal, we aim to confront this issue, using a battery of state-of-the-art methods such as paired recordings, 2-photon imaging, optogenetics, and computer modeling. Our unpublished data indicate that some interneuronal cell types possess “reversed” STDP at their excitatory inputs, while others do not. This synapse type specificity of STDP is not likely to be coincidental, but important for brain functioning. We will use this as a starting point, and trace out the STDP learning rules of key synapse types in developing visual cortex, while carefully classifying these interneurons based on their morphology, intrinsic firing patterns, and genetic markers. This research program will clarify the rules that govern information storage and rewiring during development of the neocortex. Our efforts will produce cutting-edge scientific results, while at the same time being safe. The proposal would enable three graduate students to learn advanced optical and electrophysiological techniques, and an undergraduate to learn imaging, morphological reconstructions, etc., thus providing an ideal setting for training of highly qualified personnel ranging from the junior to the relatively senior.

神经科学家认为，学习和记忆以及发育过程中神经元回路的完善是由于相互连接的神经元之间突触连接的变化（称为突触可塑性）造成的。我的团队研究新皮质的可塑性，重点关注最近发现的尖峰时间依赖性可塑性（STDP）范式，因为它具有出色的实验控制和生物学合理性。对于经典的 STDP，突触后放电之前的几毫秒内会导致增强，而相反的时间顺序会引起减弱，从而有效地使大脑能够学习因果关系。但众所周知，突触可塑性随着突触类型的不同而变化——在不同的中间神经元类别的输入中发现了不同的机制和现象学。突触可塑性为何以及如何变化？在这项发现资助提案中，我们的目标是使用一系列最先进的方法来解决这个问题，例如配对记录、2 光子成像、光遗传学和计算机建模。 我们未发表的数据表明，一些中间神经元细胞类型在其兴奋性输入上具有“反向”STDP，而其他细胞类型则没有。 STDP 的这种突触类型特异性不太可能是巧合，但对大脑功能很重要。我们将以此为起点，追踪视觉皮层发育过程中关键突触类型的 STDP 学习规则，同时根据这些中间神经元的形态、内在放电模式和遗传标记对这些中间神经元进行仔细分类。该研究计划将阐明新皮质发育过程中信息存储和重新布线的规则。我们的努力将产生尖端的科学成果，同时也是安全的。该方案将使三名研究生学习先进的光学和电生理技术，一名本科生学习成像、形态重建等，从而为培养从初级到高级的高素质人才提供了理想的环境。