Integrating flexible neural probes with a giant cranial window for combined electrophysiology and 2-photon calcium imaging of cortex-hippocampal interactions

将柔性神经探针与巨大颅窗集成，用于皮层-海马相互作用的电生理学和 2 光子钙成像相结合

• 批准号: 9197792
• 负责人: Peyman Golshani
• 金额: $ 15.26万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-23 至 2018-09-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9197792
• 关键词: Animals; Automobile Driving; BRAIN initiative; Brain; Brain region; Calcium; Cephalic; Chronic; Complex; Data; Decision Making; Electrodes; Electrophysiology (science); Environment; Fire - disasters; Funding; Goals; Grant; Head; Hippocampus (Brain); Image; Implant; Laboratories; Learning; Maps; Medial; Memory; Memory impairment; Mus; Nature; Neocortex; Neurodegenerative Disorders; Neurons; Noise; Occipital lobe; Operative Surgical Procedures; Parietal; Pattern; Performance; Polymers; Population; Prefrontal Cortex; Preparation; Public Health; Resolution; Rest; Retrieval; Running; Shapes; Short-Term Memory; Slow-Wave Sleep; Stimulus; Structure; Surface; Techniques; Technology; Testing; Time; Training; Travel; Visit; Wakefulness; Water; Work; awake; base; calcium indicator; cell type; cortex mapping; design; excitatory neuron; flexibility; implantation; laboratory development; memory encoding; memory retrieval; multisensory; neocortical; neuronal circuitry; neuropsychiatric disorder; relating to nervous system; research study; response; sensory cortex; treadmill; two-photon

Project Summary: Hippocampal sharp-wave ripples are 150-250 Hz oscillations during slow-wave sleep or immobility during which large populations of hippocampal neurons sequentially replay activity patterns that occurred during exploration of the environment. Disruption of ripples during wakefulness disrupts working memory. Recent work has shown that many other extra-hippocampal brain regions are specifically activated during ripples, and this coordination of hippocampal and neocortical networks during ripples may be critical for learning and retrieval. Yet the precise identity of cell types across different neocortical regions and reliability of activation during ripples is not known. The Golshani Laboratory has recently developed a large cranial window preparation that allows us to perform systematic and unbiased calcium imaging of neurons across all brain regions extending from frontal to occipital cortex bilaterally. Here we propose to implant flexible electrode arrays developed by the Tolosa and Frank Labs as a part of the BRAIN initiative into the hippocampus in mouse implanted with the large cranial window. These flexible electrode arrays will be optimal for this purpose because they allow long lasting recordings of local field potential for >200 days; moreover, because they are flexible they can be shaped so they don't obscure the imaging window. We will first learn implantation of electrodes by visiting the Frank Lab at UCSF. We will then obtain flexible electrode arrays from the Tolosa Lab (10 arrays), and implant them into the hippocampus in Thy-1 GCAMP6s animals with the large cranial window. After assuring that we can perform low noise electrophysiological recordings and calcium imaging in head-fixed animals resting on the treadmill, we will train animals to perform a memory retrieval task. We will determine proportion of neurons in different cortical regions activated during ripples during the task and their reliability activation across days. This one year R03 will allow us to collect data showing feasibility of these experiments that we will use as preliminary data for a collaborative BRAIN initiative grant.

项目概要： 海马尖波波纹是慢波睡眠或静止期间 150-250 Hz 的振荡，在此期间 大量海马神经元依次重放探索过程中发生的活动模式 环境的。清醒时涟漪的中断会扰乱工作记忆。最近的工作有 表明许多其他海马外大脑区域在波纹期间被特别激活，并且这 波纹期间海马和新皮质网络的协调可能对于学习和检索至关重要。 然而，不同新皮质区域细胞类型的精确识别以及波纹期间激活的可靠性 尚不清楚。 Golshani 实验室最近开发了一种大型颅窗制备装置，可以 我们对所有大脑区域的神经元进行系统且公正的钙成像 双侧额叶至枕叶皮质。在这里，我们建议植入由该公司开发的柔性电极阵列 Tolosa 和 Frank 实验室作为 BRAIN 计划的一部分，在小鼠的海马体中植入了大 颅窗。这些柔性电极阵列将是此目的的最佳选择，因为它们可以实现持久的 超过 200 天的当地现场潜力记录；此外，由于它们具有柔韧性，因此可以塑形 不要遮挡成像窗口。我们将首先参观 Frank 实验室，学习电极植入： 加州大学旧金山分校。然后，我们将从 Tolosa 实验室获取柔性电极阵列（10 个阵列），并将它们植入到 具有大颅窗的 Thy-1 GCAMP6s 动物的海马体。在保证我们可以表现低后 在跑步机上休息的头部固定动物的噪声电生理记录和钙成像中，我们将 训练动物执行记忆检索任务。我们将确定不同皮质中神经元的比例 任务期间的涟漪期间激活的区域及其在几天内的可靠性激活。这一年R03 将使我们能够收集显示这些实验可行性的数据，我们将使用这些数据作为初步数据 协作 BRAIN 倡议拨款。