In Search of the Neural Underpinnings of Temporal Binding: Linking Synaptic Depression with Neural Adaptation in Auditory Cortex

对声音的感知与时间进化密切相关：大多数声音，特别是语音，只有在感觉到之前发生的事情的背景下才有意义。这需要记忆，从而在最近的过去的连续更新的表示的上下文中表示传入的声音。我们称这一过程为时间约束。虽然时间绑定的神经基础是一个悬而未决的问题，但最近的研究表明，突触抑制可能是其关键机制之一。突触抑制可以被认为是一种局部记忆形式，很难直接观察到。然而，其可观察到的效应之一被认为是适应，这是一种感觉记忆的形式，其表现为反复刺激导致神经反应的减弱。突触抑制和适应都可以用描述从这些影响中恢复的速度的时间常数来表征。我们打算通过结合申请者在听觉皮质的计算模型、猴子听觉皮质中单个神经元活动的记录以及人类脑磁图(MEG)和脑电(EEG)测量方面的互补专业知识来调查突触抑制、适应和时间绑定之间的联系。猴子和人类受试者的这种使用将使我们能够观察到听觉皮质小神经元和大神经元群体活动的适应和时间绑定。这些观察与计算模型相结合，将形成一个强大的工具，用于揭示时间绑定的神经基础。该项目的第一部分将通过模拟和实验的方式解决突触抑制和适应之间的关系。我们的初步结果表明，这种关系不是微不足道的和复杂的，但使用多种互补的实验范式来衡量适应将使我们能够单独估计每个受试者突触抑制的恢复时间常数的值。在第二部分中，我们将利用实验中获得的人类和猴子听觉皮质突触抑制恢复时间常数的估计，来测试建模工作的预测。这将使我们能够解决听觉皮质如何代表声音序列，以及它如何区分不同元素定时的序列。这个项目是及时的，它的实现需要融合猴子电生理学、人类脑磁图/脑电和计算神经科学的专业知识。位于马格德堡的莱布尼茨神经生物学研究所是世界上为数不多的将所需的专业知识和方法集中在一个地点的研究机构之一。

The perception of sound is intimately bound with time evolution: most sounds, speech sounds in particular, make sense only when perceived against the backdrop of what came immediately before. This requires memory whereby incoming sounds are represented in the context of a continuously updated representation of the immediate past. We term this process temporal binding. While the neural underpinnings of temporal binding are an open question, recent research suggests that synaptic depression might be one of its key mechanisms. Synaptic depression could be considered a local form of memory, and it is difficult to observe directly. However, one of its observable effects is thought to be adaptation, a form of sensory memory which expresses itself as the attenuation of neural responses with repeated stimulation. Both synaptic depression and adaptation can be characterized by the time constants describing the speed with which recovery from these effects occur. We intend to investigate the link between synaptic depression, adaptation, and temporal binding by combining the complementary expertise of the applicants in computational modelling of auditory cortex, recordings of single-neuron activity in monkey auditory cortex, and magnetoencephalography (MEG) and electroencephalography (EEG) measurements in humans. This use of monkey and human subjects will allow us to observe adaptation and temporal binding in the activity of small and large neuronal populations of auditory cortex. These observations combined with computational modelling will form a powerful tool for uncovering the neural underpinnings of temporal binding. The first part of the project will address the relationship between synaptic depression and adaptation by means of simulations and experiments. Our preliminary results suggest that this relationship is non-trivial and complex, but the use of multiple, complementary experimental paradigms for measuring adaptation will allow us to estimate values of the recovery time constant of synaptic depression individually for each subject. In the second part, we will test predictions of the modelling work, utilizing the experimentally gained estimates of the recovery time constant for synaptic depression in humans and monkey auditory cortex. This will allow us to address how auditory cortex represents sound sequences and how it discriminates between sequences differing in the timing of their elements.The project is timely, and its realization requires the amalgamation of expertise in monkey electrophysiology, human MEG/EEG, and computational neuroscience. The Leibniz Institute for Neurobiology in Magdeburg is one of the few research institutes in the world which brings together, to a single site, the required expertise and methodology.