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的进化密切相关：大多数声音，尤其是语音，只有在之前的背景下才有意义。这需要记忆，通过这种方式，传入的声音在对刚刚过去的不断更新的描述中被呈现出来。我们称这个过程为时间绑定。虽然颞叶结合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形式的记忆，很难直接观察到。然而，它的一个可观察到的影响被认为是适应，一种感觉记忆的形式，表现为神经反应在反复刺激下的衰减。突触抑制和适应都可以用描述从这些影响中恢复速度的时间常数来表征。我们打算通过结合申请人在听觉皮层计算建模、猴子听觉皮层单神经元活动记录以及人类脑磁图（MEG）和脑电图（EEG）测量方面的互补专业知识，研究突触抑制、适应和时间绑定之间的联系。这种对猴子和人类受试者的使用将使我们能够观察听觉皮层大小神经元群活动的适应性和时间绑定。这些观察结合计算模型将形成一个强大的工具来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来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，但使用多个互补的实验范式来测量适应性，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，我们将测试模型工作的预测，利用实验获得的对人类和猴子听觉皮层突触抑制的恢复时间常数的估计。这将使我们能够解决听觉皮层如何表示声音序列，以及它如何区分不同时间序列的元素。这个项目很及时，它的实现需要融合猴子电生理学、人类脑电/脑电图和计算神经科学方面的专业知识。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汇集到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.