Cellular-based Mechanisms Underlying Oscillatory Brain Dynamics

大脑是如何工作的？有节奏的大脑活动是大脑记录中的一个共同特征，现在有很多证据表明，在我们的大脑回路中产生这些节奏是我们的大脑组织信息的一种方式。然而，这些节奏是如何产生的还远不清楚。大脑的复杂网络是一个值得欣赏的挑战，因为大脑的多尺度性质及其无数的生物学细节。我们迫切需要数学模型来帮助我们解决这种复杂性，但如果我们想要理解生物系统，而不仅仅是数学模型系统，那么与我们模型的实验相互作用需要清楚。我的实验室的长期目标是确定振荡网络动力学背后的基于细胞的机制，我们在研究的初始阶段通过理论、实验和建模相结合的方式来做到这一点。重要的是要注意到，确定基于细胞的理解是至关重要的，因为我们知道细胞的特殊性很重要。*在这项提案中，我将重点放在特定的节律，特别是大脑结构上，以使我们能够包括生物学细节，并与实验研究密切联系。Theta(3-12赫兹)和伽马(25-140赫兹)节律及其在大脑中被称为海马体的区域的组合是我们关注的焦点。这是因为海马体中的这些节律不仅在记忆处理和空间导航中是必不可少的，而且已经被证明是大脑编码方案的组成部分。为了理解这些节律的产生，我们将建立神经元和神经元网络的计算模型，这些神经元和神经元网络以抑制性细胞类型为中心，因为它们表达了广泛的多样性，并以特定的方式控制这些节律。我们的一般方法是将我们的神经元和神经元网络模型的开发和分析与明确定义的实验环境中的数据紧密结合起来。通过这种方式，可以检验从我们的模型中产生的预测和假设。我们与实验学家和数学家合作，使我们能够获得实验数据，并能够利用深度理论。*鉴于这些节律对大脑工作的重要性，我们的工作所达成的任何理解都将是神经科学界的根本利益所在。此外，它还将为理解大脑回路出错时的神经疾病提供基础，并反映在这些节律的调节上。

How does the brain work? Rhythmic brain activities are a common feature in brain recordings and there is now much evidence indicating that the generation of these rhythms in our brain circuits is a way in which our brains work to organize information. However, it is far from clear how these rhythms are generated. The complex networks of the brain are a challenge to appreciate because of the multi-scale nature of the brain along with its myriad of biological details. Mathematical models are strongly needed to help us tackle this complexity, but experimental interactions with our models need to be clear if we are to achieve an understanding of the biological system, and not only the mathematical model system. The long-term goal of my lab is to determine cellular-based mechanisms underlying oscillatory network dynamics, and we do this by combining theory, experiment and modeling at initial stages of the research. It is important to note that determining a cellular-based understanding is critical as we know that cell specifics matter. ******In this proposal I focus on particular rhythms in particular brain structures to allow us to include biological details and to closely interface with experimental studies. Theta (3-12 Hz) and gamma (25-140 Hz) rhythms and combinations of them in a region of the brain called the hippocampus are our focus. This is because these rhythms in the hippocampus are not only known to be essential in memory processing and spatial navigation, but have also been shown to be components of the brain's coding scheme. To understand the generation of these rhythms, we will build computational models of neurons and networks of neurons that are centered on inhibitory cell types since they express a wide diversity and are controllers of these rhythms in specific ways. Our general approach is to closely align our neuronal and neuronal network model development and analyses with data in well-defined experimental contexts. In this way, predictions and hypotheses that arise from our models can be tested. We collaborate with both experimentalists and mathematicians allowing us to have access to experimental data and to be able to harness in depth theory. ******Given the importance of these rhythms to brain workings, any understanding achieved by our work would be of fundamental interest to the Neuroscience community. As well, it would provide a basis to understand neurological disease when brain circuits go awry and are reflected in modulation of these rhythms.*****