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解开控制动物行为的神经回路和处理。更好地了解这些系统可以帮助治疗目前使用侵入性脑深部刺激缓解的疾病。因此，神经元活动的非侵入性远程控制方法是许多神经科学家愿望清单的顶部。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进行物理连接。该提案的目的是证明交变磁场可用于刺激哺乳动物大脑深处的神经元，方法是使用纳米颗粒将磁场能量转化为局部热，并在基因上表达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，因此非常适合深部组织刺激。所使用的场和频率将与标准MRI机器中使用的场和频率相当。 该方法包含几个极具创新性和新颖性的概念：（1）磁神经刺激，（2）将磁场转化为热以产生局部和生物学可检测的刺激，（3）将纳米颗粒靶向细胞膜以实现加热的亚细胞定位，（4）利用神经元基因工程合成磁性纳米粒子都是新颖的创新思想。这项研究非常重要，因为它提供了一种研究神经元回路与动物行为关系的方法。这种能力将（i）增加我们对正常和病理性脑功能的理解，以及（ii）为自然刺激减少的条件下的远程刺激提供新的治疗途径，例如创伤性脑损伤，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.