Transparent graphene electrode arrays for simultaneous electrical and optical investigation of computations in the olfactory bulb

项目摘要和摘要 理解行为和神经元活动之间的联系的一个主要障碍是 电生理学记录大量神经元群体的活动，而不限制视觉接触。电极，电极 阵列直接测量电信号，并提供比光学信号高得多的时间分辨率 荧光技术，但由此产生的光学访问障碍限制了电极阵列配对的能力 有光遗传刺激和钙质成像。为了更好地将这些工具配对，一种新的方法 需要神经元-电极接口。我们计划制备高密度的活性石墨烯阵列 用于活体应用的透明柔性衬底上的设备。这一新颖的设计将解决关键问题 体内神经记录技术领域取得进展的障碍：信号强度提高，时间性高 高分辨率、高传感器密度，以及与透明的独特方面改进的生物兼容性。 在第一个目标中，我们将开发一种表面石墨烯电极阵列。最重要的是， 制造将允许我们通过对GEA设计的轻微更改进行迭代，例如电极几何形状和 支撑层的灵活性通过分形切割来优化其模拟环境的能力。这 仿生设计将通过与感兴趣的细胞更密切地接触而产生更高的灵敏度，同时 最大限度地减少对长期录音的损害。场效应响应引起的局部信号放大 石墨烯的合成将导致一种具有前所未有的生物兼容性和灵敏度的装置。这 首先将应用透明的GEA来记录嗅球的感觉输入活动，位于 位于大脑表面的肾小球。为了验证这个阵列，我们将把这个感官输入与GEA一起成像 正在录音。这将使我们能够确定GEA是否能忠实地恢复OB的空间格局 肾小球反应。然后我们将实现这个数组来映射感觉神经元之间的传递函数 OB的输入和输出神经元。 在第二个目标中，我们将把GEA插入大脑深处，并从颗粒细胞记录下来，这是一个群体 位于大脑深处的小中间神经元，它们与OB的输出神经元形成相互突触。 当从颗粒细胞进行电子记录时，我们将对输出神经元中的钙信号进行成像。比较 这些记录将阐明这些神经元执行的计算。总而言之，这些实验将 揭示当信息在神经回路中的不同细胞类型之间移动时信息是如何转换的。此外, 这项工作将使GEA成为研究神经回路的有力工具。

Project Summary and Abstract A major obstacle to understanding the link between behavior and neuronal activity is the difficulty of electrophysiologically recording the activity of large neuronal populations without limiting visual access. Electrode arrays directly measure electrical signals and offer significantly greater temporal resolution than optical fluorescence techniques, but the resulting obstruction of optical access limits the ability to pair electrode arrays with optogenetic stimulation and calcium imaging. In order to better pair these tools, a new approach to the neuron-electrode interface is required. We propose to fabricate a high-density array of active graphene devices on a transparent flexible substrate for in vivo applications. This novel design will address critical barriers to progress in the field of in vivo neural recording technology: improved signal strength, high temporal resolution, high sensor density, and improved biocompatibility with the unique aspect of transparency. In the first aim, we will develop a surface graphene electrode array (GEA). Critically, the ease of fabrication will allow us to iterate through slight alterations to the GEA design, such as electrode geometry and the flexibility of the support layer through fractal cuts to optimize its ability to mimic the environment. This biomimetic design will result in higher sensitivity through more intimate contact with cells of interest while minimizing damage for long term recordings. The local signal amplification resulting from the field effect response of graphene will make result in a device with an unprecedented level of biocompatibility and sensitivity. This transparent GEA will first be applied to record the activity of the sensory input to the olfactory bulb, located in glomeruli at the surface of the brain. To validate this array, we will image this sensory input in concert with GEA recording. This will allow us to determine whether the GEA can faithfully recover the spatial pattern of OB glomerular responses. We will then implement this array to map the transfer function between the sensory neuron inputs and the output neurons of the OB. In the second aim, we will insert the GEA deep into the brain and record from granule cells, a population of small interneurons located deep in the brain, which form reciprocal synapses with the output neurons of OB. While recording electrically from granule cells, we will image calcium signals in the output neurons. Comparison of these recordings will elucidate the computations that these neurons perform. Together, these experiments will reveal how information is transformed as it moves between different cell types within a neural circuit. In addition, this work will establish GEAs as a powerful tool for investigating neural circuits.