CRCNS: Collaborative Research: The Role of Dendritic Processing in Persistent Neural Activity

在几秒到几十秒的时间尺度上的记忆被存储为神经活动的模式，这种模式在刺激抵消后持续很长时间。这种持续的神经活动被认为对处理新信息和形成认知感知至关重要。最近的研究表明，纯粹基于电路的机制不足以解释持续活动对生物噪声和扰动的稳健性。这一提议将检验一种假说，即持续活动是由一种混合的细胞/电路机制维持的，在这种机制中，电路级反馈介导了神经元树突中被称为平台电位的记忆过程的激活。为了定量地了解活性树突特性如何对持续活动做出贡献，将开发一个新的建模框架，以直接和同时将记忆网络与来自一系列不同实验的数据相匹配，这些实验表征了固有的兴奋性、解剖连接、神经编码和对扰动的反应。这些模型将被用来预测可以用荧光钙成像观察到的树突状细胞活动模式。为了验证这些预测，斑马鱼制剂将被用来直接测量眼球运动行为中存储所需眼部位置记忆的细胞的树突活动。钙指示剂的双光子成像将被用来测量树突神经束中活动的时空模式，以及单独在树突小枝中的活动，以确定平台电位的存在。总之，这些计算和实验结果将有助于确定细胞和电路属性如何协同工作，以产生最重要的大脑动力学之一--持久的神经活动。

Memories on the time scale of seconds to tens of seconds are stored as patterns of neural activity that persist long after the offset of a stimulus. This persistent neural activity is believed to be critical for processing new information and forming cognitive perceptions. Recent studies suggest that purely circuit-based mechanisms are insufficient to explain the robustness of persistent activity to biological noise and perturbation. This proposal will test the hypothesis that persistent activity is maintained by a hybrid cellular/circuit mechanism in which circuit level feedback mediates the activation of memory processes in a neuron's dendrites known as plateau potentials. To quantitatively understand how active dendritic properties contribute to persistent activity, a new modeling framework will be developed to directly and simultaneously fit a memory network to data from a diverse set of experiments characterizing intrinsic excitability, anatomical connectivity, neural coding, and response to perturbations. These models will be used to predict the patterns of dendritic activity that can be seen with fluorescence calcium imaging. To test these predictions, the zebrafish preparation will be used to directly measure dendritic activity during eye movement behavior from cells storing a memory of desired eye position. Two-photon imaging of calcium indicators will be used to measure spatiotemporal patterns of activity in the dendritic neuropil, and separately in individual dendritic branchlets, to determine the presence of plateau potentials. Together, these computational and experimental results will help determine how cellular and circuit properties work in concert to generate one of the most important brain dynamics, persistent neural activity.