Deep Tissue Magneto-Genetic Cell-Stimulation for Neuroscience and Therapy

描述（由申请人提供）：神经科学的一个主要目标是揭示控制动物行为的神经回路和处理。对这些系统的深入了解可以帮助治疗目前使用侵入性深部脑刺激减轻的疾病。因此，非侵入性、远程控制神经元活动的方法是许多神经科学家最想要的。目标是开发一种方法来刺激大脑深处的特定神经元子集，而不需要与外部世界建立物理连接。这个提议的目的是证明交替磁场可以用来刺激哺乳动物大脑深处的神经元，通过使用纳米颗粒将磁场能量转化为局部热量，并通过基因表达一个温度敏感的离子通道，然后将热刺激转化为膜去极化。磁场与组织的相互作用很弱，因此非常适合用于深层组织刺激。所使用的场和频率将与标准核磁共振成像仪中使用的场和频率相当。该方法包含了几个非常创新和新颖的概念：(1)磁神经刺激，(2)将磁场转化为热量以产生局部和生物可检测的刺激，(3)将纳米颗粒靶向细胞膜以实现加热的亚细胞定位，以及(4)神经元基因工程合成磁性纳米颗粒都是新颖和创新的想法。这项研究非常重要，因为它提供了一种研究动物行为与神经元回路关系的方法。这种能力将(i)增加我们对正常和病理脑功能的理解，（ii）为自然刺激减少的情况下的远程刺激提供新的治疗途径，如创伤性脑损伤、帕金森病、肌张力障碍或重度抑郁症。

DESCRIPTION (provided by applicant): One major goal of neuroscience is to unravel the neural circuitry and processing that control animal behaviors. A greater understanding of these systems can help in the treatment of diseases which are currently alleviated using invasive deep brain stimulation. Hence, methods for non-invasive, remote control of neuronal activity are at the top of the wish list for many neuroscientists. The goal is to develop a method to stimulate specific subsets of neurons deep in the brain without requiring a physical connection to the outside world. The objective of this proposal is to demonstrate that alternating magnetic fields may be used to stimulate neurons deep inside mammalian brains by using nanoparticles to convert the magnetic field energy into localized heat and genetically expressing a temperature sensitive ion-channel which then converts the heat stimulus into membrane depolarization. Magnetic fields interact only weakly with tissue, making them well suited for deep tissue stimulation. The fields and frequencies used will be comparable to those used in standard MRI machines. The approach contains several extremely innovative and novel concepts: (1) magnetic neuro- stimulation, (2) conversion of magnetic fields into heat to create a local and biologically detectable stimulus, (3) targeting nanoparticles to the cell membrane to achieve sub-cellular localization of the heating, and (4) genetic engineering of neurons to synthesize magnetic nanoparticles are all novel and innovative ideas. The proposed research is highly significant because it provides a method by which the relationship of neuronal circuits to animal behavior can be studied. This capability will (i) increase our understanding of normal and pathological brain function, and (ii) provide new therapeutic avenues for remote stimulations in conditions with reduced natural stimulations, such as traumatic brain injuries, Parkinson's disease, dystonia or major depression.