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

描述(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过程。对这些系统的更多了解可以帮助治疗目前通过侵入性脑深部刺激缓解的疾病。因此，对许多神经学家来说，非侵入性、远程控制神经元活动的方法是他们最想要的。其目标是开发一种方法来刺激大脑深处的特定神经元亚群，而不需要与外部世界建立物理连接。这项提议的目的是证明交变磁场可以用来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，这使得它们非常适合于深层组织刺激。所使用的磁场和频率将与标准MRI机器中使用的场和频率相当。该方法包含了几个极其创新和新颖的概念：(1)磁神经刺激，(2)将磁场转化为热以产生局部和生物可检测的刺激，(3)将纳米颗粒靶向细胞膜，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颗粒，这些都是新颖的创新想法。这项拟议的研究具有非常重要的意义，因为它提供了一种方法，可以用来研究神经元回路与动物行为的关系。这种能力将(I)增加我们对正常和病理大脑功能的了解，(Ii)为在自然刺激减少的情况下进行远程刺激提供新的治疗途径，如创伤性脑损伤、帕金森氏症、肌张力障碍或严重抑郁症。

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.