Synapse-type-specific plasticity in neocortical microcircuits

神经学家认为，学习和记忆以及发育过程中神经元电路的细化是由于相互连接的神经元之间的突触连接发生了变化，这被称为突触可塑性。我的团队研究新大脑皮层的可塑性，重点是最近发现的依赖于峰的可塑性(STDP)范式，因为它具有出色的实验控制和生物学上的合理性。对于经典的STDP，在突触后几毫秒内放电之前的前几毫秒会导致增强，而相反的时间顺序会导致减弱，这有效地使大脑能够学习因果关系。但众所周知，突触的可塑性随着突触类型的不同而不同--在不同神经元间类的输入端发现了不同的机制和现象学。为什么以及如何改变突触的可塑性？在这份探索基金提案中，我们的目标是解决这个问题，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. 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.