Collaborative Research: The Hemo-Neural Hypothesis

拟议中的研究将验证一个新的假设，即增强局部大脑区域的血液供应会影响神经处理。神经回路的一个关键特征是它们的灵活性，即它们根据环境做出不同反应的能力（例如，对感官刺激的反应）。这种灵活性使生物体，特别是人类能够完成生存的关键任务，比如转移注意力。这种灵活性对大脑健康也至关重要：正常的神经动力学机制失效？在正常的能力转移灵敏度？与从癫痫到精神分裂症等疾病有关。在这个项目中，pi将测试一种预测，即皮层感觉神经元血液供应的变化可以调节它们对感觉输入的反应。为了验证这一假设，他们将整合四种技术，汇集来自两个实验室的专业知识：全动物电生理和成像研究，以确定血流变化对神经活动的影响；脑切片电生理和成像研究，开始研究这种现象背后的机制。提出的研究的一个关键特征是开发一种双向血流调节的新手段，将光激活通道病毒转染到平滑肌中。通过使用定向光收缩或放松平滑肌，它们将扩张或收缩局部脑小动脉，调节血液供应。这种方法提供了一种独立于药物干预的潜在混淆的方法。拟议研究的第二个关键特征是麻省理工学院皇后学院学生的暑期研究计划。这个项目将为皇后学院的学生提供一个独特的机会，让他们体验麻省理工学院的环境，在研究计划的制定、计划的执行、研究伦理的培训以及撰写论文摘要方面进行系统的培训。

The proposed research will test the novel hypothesis that enhanced blood supply to a local brain region impacts neural processing. A key feature of neural circuits is their flexibility, their ability to respond differently (for example, to a sensory stimulus) depending on context. This flexibility allows organisms in general and humans in particular to perform crucial tasks for survival, such as shifting attention. This flexibility is also crucial to brain health: Failures in normal mechanisms of neural dynamics?in the normal ability to shift sensitivity?have been implicated in diseases ranging from epilepsy to schizophrenia.In this project the PIs will test the prediction that changes in blood supply to cortical sensory neurons can modulate their responses to sensory inputs. To test this hypothesis, they will integrate four techniques, bringing together expertise from two laboratories: whole animal electrophysiological and imaging studies to define the effect of changes in blood flow on neural activity and electrophysiological and imaging studies in brain slices to begin to investigate the mechanisms underlying this phenomenon. A key feature of the proposed research is development of a novel means of bidirectional blood flow regulation, the viral transfection of light-activated channels into smooth muscle. By constricting or relaxing smooth muscles using directed light, they will expand or contract local cerebral arterioles, regulating blood supply. This method provides an approach independent of the potential confounds of pharmacological intervention. A second key feature of the proposed research is a summer research initiative for Queens College students at MIT. This program will provide a unique opportunity for Queens College students to experience the MIT environment, systematic training in research proposal development, execution of this plan, training in research ethics, and writing a summary for publication.