Synaptic Plasticity in Neocortical Interneurons

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的突触连接的变化，称为突触可塑性。一般来说，我的团队研究新皮层的可塑性，但我们专注于最近发现的尖峰时间依赖可塑性（STDP）范式，因为它具有良好的实验控制和生物可操作性。在经典的STDP中，突触前和突触后放电在几毫秒内会导致强化，而相反的时间顺序会导致弱化，这有效地使大脑能够学习因果关系。但是，突触可塑性是众所周知的不同细胞类型-不同的机制和现象被发现在不同的中间神经元类。突触可塑性为何以及如何变化？在这个发现补助金提案中，我们的目标是面对这个问题，使用一系列最先进的方法，如配对记录，双光子成像，光遗传学和计算机建模。

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. Generally speaking, my team investigates plasticity in neocortex, but we focus on the 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 cell type -- different mechanisms and phenomenology are found in 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.