Optogenetic tools to distinguish neuronal class in behaving non-human primates

光遗传学工具可区分非人类灵长类动物的神经元类别

• 批准号: 8771361
• 负责人: CORY T MILLER
• 金额: $ 30.7万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8771361
• 关键词: 6-Cyano-7-nitroquinoxaline-2,3-dione; AMPA Receptors; Action Potentials; Animals; Area; Attention deficit hyperactivity disorder; Autistic Disorder; Behavior; Biological Assay; Biological Models; Breeding; Callithrix; Callithrix jacchus jacchus; Cebidae; Cells; Cercopithecidae; Charge; Cortical Column; Data; Development; Disease; Electrodes; Foundations; Glutamates; Goals; Head; Homologous Gene; Interneurons; Label; Lasers; Light; Location; Membrane Potentials; Methodology; Methods; Modeling; Monkeys; Mus; N-Methyl-D-Aspartate Receptors; Neurons; Opsin; Parvalbumins; Penetration; Physiologic pulse; Population; Primates; Relative (related person); Research; Response Latencies; Role; Schizophrenia; Sensory; Series; Serotyping; Site; Source; Stimulus; Subfamily lentivirinae; Surface; Synapsins; Syndrome; Target Populations; Techniques; Testing; Time; Transgenic Mice; Transgenic Organisms; Use of New Techniques; Visual; Visual Agnosias; area V2; area striata; awake; base; density; excitatory neuron; extracellular; extrastriate visual cortex; falls; genetic manipulation; interest; neglect; nervous system disorder; neural circuit; neuromechanism; neurophysiology; neuropsychological; nonhuman primate; novel; optogenetics; promoter; public health relevance; response; restraint; tool

DESCRIPTION (provided by applicant): A major obstacle to understanding the neural mechanisms underlying behavior is our inability to distinguish between neuronal classes in recordings from behaving animals. Mouse transgenic lines, including CRE lines, have made it possible to use optogenetic techniques to selectively activate different classes to determine their role in behavior. However, it remains a challenge to determine the neuronal identity based on optogenetic stimulation, as the latency of response to direct stimulation can overlap with strong but indirect disynaptic excitation. The proposed research will introduce novel methods for distinguishing direct from indirect stimulation in order to label neuronal identity. It will furthe develop these methods for extracellular recordings made with linear array electrodes and using current source density (CSD) analysis to identify laminar location. These methods will be validated in CRE mice, and then applied to the marmoset (Callithrix jacchus). The marmoset is a particularly interesting primate model because it offers opportunities for dissecting neural circuitry that are comparable to the mouse. It matures quickly and breeds well in captivity, so it is amenable to the kinds of genetic manipulation used in mice and has produced the first primate transgenic lines. It also has a lissencephalic (flat) cortex which aids in laminar recordings. Preliminary data show marmosets can perform visual tasks under head-restraint, making them suitable to awake neurophysiology. Establishing these methods will create opportunities to study cortical circuits at a mechanistic level, enabling the field to understand how aberrations in the cortical circuitry give rise to devastating disorders such as schizophrenia and autism.

描述（由申请人提供）：理解神经机制的主要障碍是我们无法区分录音中的神经元类别与行为动物。小鼠转基因线，包括CRE系，使使用光遗传技术有可能有选择地激活不同的类别以确定其 在行为中的作用。然而，确定基于光遗传学刺激的神经元同一性仍然是一个挑战，因为对直接刺激的响应潜伏期可能与强但间接的双突触激发重叠。拟议的研究将引入新的方法，以区分间接刺激，以标记神经元同一性。它将为用线性阵列电极制成的细胞外记录开发这些方法，并使用电流源密度（CSD）分析来识别层流位置。这些方法将在CRE小鼠中进行验证，然后应用于Marmoset（Callithrix Jacchus）。 Marmoset是一个特别有趣的灵长类动物模型，因为它为解剖与小鼠相当的神经电路提供了机会。它迅速成熟并在囚禁中繁殖得很好，因此它可以适合小鼠使用的遗传操纵种类，并产生了第一个灵长类动物的转基因线。它还具有lissphalic（Flat）皮层，可帮助层流录音。初步数据表明，Marmosets可以在头部延伸下执行视觉任务，使其适合清醒神经生理学。建立这些方法将创造机会在机械水平上研究皮质回路，从而使该领域了解皮质电路中的像差如何导致诸如精神分裂症和自闭症之类的毁灭性疾病。