Testing the Hemo-Neural Hypothesis: Tetrode, Two-photon & Computational Studies

测试血液神经假说：四极管，双光子

• 批准号: 7810264
• 负责人: Nathan E Vierling-Claassen
• 金额: $ 5.05万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7810264
• 关键词: Action Potentials; Astrocytes; Biological Neural Networks; Blood; Blood Vessels; Calcium; Cells; Computer Simulation; Coupling; Data; Development; Disinhibition; Down-Regulation; Elements; Epilepsy; Event; Fellowship; Figs - dietary; Foundations; Functional Magnetic Resonance Imaging; Future; Gated Ion Channel; Hyperemia; Image; Individual; Instruction; Interdisciplinary Study; Interneurons; Knowledge; Label; Lead; Measures; Mediating; Membrane; Mentors; Migraine; Modeling; Mus; Names; Neuroglia; Neurologic; Nitric Oxide; Parvalbumins; Photons; Physiological; Positioning Attribute; Process; Pyramidal Cells; Rattus; Regulation; Research; Sensory; Signal Transduction; Smooth Muscle; Source; Stroke; System; Techniques; Temperature; Testing; Training; Vascular blood supply; Vibrissae; Work; barrel cortex; base; cell type; computer studies; hemodynamics; hippocampal pyramidal neuron; in vivo; neural model; neuroimaging; novel; relating to nervous system; research study; response; therapeutic development; therapeutic target; two-photon

DESCRIPTION (provided by applicant): Neural activity creates a spatio-temporally localized increase in blood supply known as functional hyperemia, known to underlie neuroimaging signals such as functional magnetic resonance imaging. The 'Hemo-Neural hypothesis,' recently proposed by sponsor Dr. Christopher Moore, predicts that hyperemia may also modulate neural excitability. Hemo-Neural influence may be mediated indirectly via glial cells or directly by temperature change, blood borne diffusible messengers such as nitric oxide, or activation of force-gated ion channels in neural membranes. I will test the specific hypotheses that hyperemia enhances the sensory response of pyramidal neurons, and diminishes the response of fast-spiking interneurons in mouse barrel cortex. I will test these predictions using a two-fold approach that combines physiological experimental techniques of tetrode recording and two-photon imaging with biophysically realistic computational modeling. These techniques will be used to test the activation of fast spiking interneurons and pyramidal cells in baseline and pharmacalogically induced hyperemia. Use of mice will allow me to identify genetically labeled specific cell-types in the 2-photon portion of my research. My results will direct the development of a computational model of a cortical neural and vascular network, from which we will investigate how hemo-induced effects may modulate neural activity. From the model, we will develop quantitative predictions of the direct effects of hyperemia on network activity that will guide future experiments. Abnormal interactions between the vascular and neural systems are associated with many neurological illnesses, including Alzhelmers, migraine, stroke and epilepsy, though these interactions have not been a subject of therapeutic development. Thus, the experimental and computational work proposed here may lay the groundwork for study of a new class of possible therapeutic targets in these conditions. PHS 416-1 (Rev. 9/08) Page 2 Number pages consecutively at the bottom throughout Form Page 2 the application. Do not use suffixes such as 2a, 2b. Kirschstein-NRSA Individual Fellowship Application NAME OF APPLICANT (Last, first, middle initial) Vierling-Claassen, Dorea L (To be completed by applicant- follow PHS 416-1 Instructions) 18.

描述（由申请人提供）：神经活动产生了被称为功能性充血的血液供应的时空局部增加，已知其是神经成像信号（如功能性磁共振成像）的基础。最近由发起人克里斯托弗摩尔博士提出的“血液-神经假说”预测，充血也可能调节神经兴奋性。血液-神经影响可通过神经胶质细胞间接介导，或通过温度变化、血液传播的可扩散信使（如一氧化氮）或神经膜中力门控离子通道的激活直接介导。我将测试特定的假设，即充血增强锥体神经元的感觉反应，并减少在小鼠桶皮质的快速尖峰中间神经元的反应。我将测试这些预测使用一个双重的方法，结合生理实验技术的四极管记录和双光子成像与生物物理学现实的计算建模。这些技术将用于检测基线和药物诱导充血中快速尖峰中间神经元和锥体细胞的激活。使用小鼠将使我能够在我的研究的双光子部分中识别遗传标记的特定细胞类型。我的研究结果将指导皮质神经和血管网络的计算模型的发展，我们将研究血液诱导的效应如何调节神经活动。从该模型中，我们将开发充血对网络活动的直接影响的定量预测，这将指导未来的实验。血管和神经系统之间的异常相互作用与许多神经系统疾病有关，包括阿尔茨海默病、偏头痛、中风和癫痫，尽管这些相互作用尚未成为治疗发展的主题。因此，这里提出的实验和计算工作可能为研究这些条件下一类新的可能的治疗靶点奠定基础。PHS 416-1（修订版9/08）第2页在整个表格第2页的底部连续编号。不要使用后缀，如2a，2b。Kirschstein-NRSA个人奖学金申请申请人姓名（最后，第一，中间首字母）Vierling-Claassen，Dorea L（由申请人填写-按照PHS 416-1说明）18。