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.

项目摘要： 海马锋利波纹波为150-250 Hz的慢波睡眠或不动时的振荡 大量的海马神经元依次重播活动模式 环境。清醒期间涟漪的破坏会破坏工作记忆。最近的工作有 表明许多其他海马外脑区域是在波纹期间特别激活的，这 波纹期间海马和新皮质网络的协调对于学习和检索至关重要。 然而，跨不同新皮质区域的细胞类型的精确身份以及波纹期间激活的可靠性 不知道。 Golshani实验室最近开发了大型的颅窗准备，允许 我们要对所有大脑区域的神经元进行系统和公正的钙成像 双侧额叶至枕皮层。在这里，我们建议植入由 Tolosa和Frank Labs作为大脑倡议的一部分，以植入大的小鼠中的海马 颅窗。这些柔性电极阵列将是最佳的，因为它们允许持久 记录当地现场潜力> 200天；而且，因为它们很灵活，它们可以被塑造，所以它们 不要掩盖成像窗口。我们将首先通过访问弗兰克实验室来学习电极的植入 UCSF。然后，我们将从tolosa实验室（10个阵列）获得柔性电极阵列，然后将其植入 Thy-1 Gcamp6s动物中的海马，带有大颅窗。保证我们可以表现较低 落在跑步机上的噪声电生理记录和钙成像，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 任务过程中的涟漪及其可靠性激活在几天内激活的区域。这一年R03 我们将允许我们收集显示这些实验可行性的数据，这些实验将用作A的初步数据 协作大脑倡议赠款。