Information Processing in the Olfactory Bulb: Plasticity and Neurogenesis

这个项目的目标是开发一个数学模型，描述大脑中嗅觉信息的初始处理，这是在嗅球中执行的。一般的信息论考虑以及实验表明，嗅球的主要任务是去关联气味刺激。它这样做的能力敏感地取决于神经网络的连通性和气味环境之间的匹配。该项目将专注于球状神经网络的能力，使其适应动物不断变化的嗅觉环境，同时保留辨别和识别先前重要气味的能力。为了模拟网络的可塑性，将包括突触的Hebbian长时程增强以及嗅球的一个几乎独特的特征--实质性的神经发生。首先，这项研究的目标是建立生物物理学上看似合理的突触可塑性规则，使由此产生的网络能够有效地解除气味输入的关联。然后，将研究仅由神经发生和细胞死亡导致的网络，并评估它们解除输入关联的能力。最后，突触可塑性和神经发生可塑性将结合在一起。预计在完整的模型中，突触的可塑性将在神经发生设置的连接框架内提供快速微调的适应，这反过来将保留关于过去环境的重要信息。在数学上，该模型将由一个由加权节点和链接组成的共同进化的二部网络组成。计算和渐近解方法将被开发来有效地处理网络结构的离散、随机演化和其权重的连续确定性演化的组合，分别涉及与神经活动、突触可塑性和网络连通性相关的三个不同的时间尺度。大脑的一个中心功能是从它从感官接收的信息中提取相关特征，并根据新的和先前存储的信息做出决策。执行第一次信息处理的大脑区域通过提供有助于提取相关信息的环境的内部表示而发挥重要作用。神经科学的一个重要目标是理解这些内部表征以及它们如何依赖于手头的任务。与视觉相比，视觉在理解动物在自然环境中看到的视觉场景的神经编码方面取得了很大进展，而嗅觉系统中气味信息的处理则少得多。与视觉世界不同，嗅觉世界是高维的，其特征随着时间的推移(季节、迁徙等)而发生显著变化。随着动物对这些变化的适应，特定气味的内部表现也可能发生变化。如果是这样的话，同样的玫瑰会被认为闻起来像春天的一朵花，秋天的另一朵花，动物将很难识别气味。这个项目的目标是阐明嗅觉系统如何应对相互冲突的任务，即适应不断变化的环境和在不同环境中可靠地识别重要气味。该模型的一个中心组成部分将是在动物整个生命过程中在嗅觉系统中观察到的新神经元的大量诞生(神经发生)。从这个项目中获得的见解很可能对“人工鼻子”的设计有用。该项目还将阐明海马体中神经发生的作用，在海马区，改变的神经发生与情绪障碍和神经退行性疾病有关。

The goal of this project is to develop a mathematical model of the initial processing of olfactory information in the brain, which is performed in the olfactory bulb. General information-theoretic considerations as well as experiments indicate that the main task of the olfactory bulb is to decorrelate odor stimuli. Its ability to do so depends sensitively on a match between the connectivity of the neural network and the odor environment. The project will focus on the ability of the bulbar neural network to adapt its connectivity to changing olfactory environments of the animal, while retaining the ability to discriminate and recognize significant previous odors. To model the plasticity of the network Hebbian long-term potentiation of the synapses will be included as well as the substantial neurogenesis that is an almost unique feature of the olfactory bulb. First the research will aim to establish biophysically plausible synaptic plasticity rules that enable the resulting network to decorrelate its odor inputs effectively. Then networks resulting from neurogenesis and cell death alone will be studied and their ability to decorrelate inputs will be assessed. Finally, synaptic and neurogenetic plasticity will be combined. It is expected that in the full model synaptic plasticity will provide fast fine-tuning of the adaptation within the connectivity framework set by neurogenesis, which in turn will retain significant information about past environments. Mathematically, the model will consist of a co-evolving bipartite network of weighted nodes and links. Computational and asymptotic solution methods will be developed to deal efficiently with the combination of discrete, stochastic evolution of the network structure and continuous deterministic evolution of its weights, involving three different time scales associated with neural activity, synaptic plasticity, and network connectivity, respectively.A central function of the brain is to extract relevant features from the information it receives from the sensory organs and to make decisions based on new and previously stored information. The brain areas that perform the first information processing play an essential role by providing an internal representation of the environment that facilitates the extraction of relevant information. An important goal in neuroscience is to understand these internal representations and how they depend on the task at hand. In contrast to vision, where great progress has been made in understanding the neural encoding of the visual scenes that an animal is seeing in its natural environment, the processing of odor information in the olfactory system is much less understood. Unlike the visual world the olfactory world is high-dimensional and its characteristic features change significantly over time (seasons, migration, etc.). As the animal adapts to these changes the internal representation of a given odor is likely to change, as well. If this were the case the same rose would be perceived as smelling like one flower in spring and like another flower in fall, say, and the animal would have difficulties to identify odors. The goal of this project is to elucidate how the olfactory system copes with the conflicting tasks of adapting to changing environments and recognizing significant odors reliably in different environments. A central component of the model will be the substantial birth of new neurons (`neurogenesis') that is observed in the olfactory system throughout the life of the animal. The insights gained in this project are likely to be useful for the design of `artificial noses'. The project will also shed light on the role of neurogenesis in the hippocampus, where altered neurogenesis has been associated with mood disorders and neurodegenerative diseases.