Miniature Microdrive for Intracellular Recordings in Freely Behaving Mice

描述（由申请人提供）：通过细胞外电极测量的动作电位是计算的冰山一角，在它下面操作着一个巨大的电化学信号系统，包括快速神经递质，神经调节剂，激素，结合这些信号分子的受体，以及这些受体所在的神经元的固有膜特性。因此，通常用于研究自由行为动物的神经活动的细胞外电极对广泛的大脑活动是盲目的。这种不敏感限制了我们对正常脑功能背后的神经机制的理解，也限制了我们对神经和神经精神疾病背后的紊乱神经活动的了解。要克服这一限制，就需要能够克服从自由行为的动物大脑神经元中获取细胞内记录这一艰巨挑战的技术。本提案旨在通过实现三个特定目标来克服这一挑战：1)开发一种微型微驱动器，其中细胞内电极可以快速加载并灵活地定位于大脑表面。2)使驱动器的体积和质量小型化，使一只老鼠可以轻松携带至少两个设备，从而便于评估神经元和大脑区域之间的功能连接。3)对行为自由的小鼠的听觉皮层进行细胞内记录，因为它们在已知的强烈调节听觉反应的条件下处理听觉刺激。这项技术的改进将广泛有利于神经科学界，其在小鼠中的应用将为分析紊乱的神经活动如何成为疾病的基础打开大门。！

DESCRIPTION (provided by applicant): The action potentials measured by an extracellular electrode are the tip of a computational iceberg, beneath which operates a vast electrochemical signaling system involving fast neurotransmitters, neuromodulators, hormones, the receptors that bind these signaling molecules, and the intrinsic membrane properties of the neurons in which these receptors reside. Consequently, the extracellular electrodes commonly used to study neural activity in freely behaving animals are blind to a wide spectrum of brain activity. This insensitivity limits our understanding of the neural mechanisms underlying normal brain function and also limits insights into disordered neural activity that underlies neurological and neuropsychiatric diseases. Surmounting this limitation requires technology that can overcome the formidable challenge of obtaining intracellular recordings from neurons in the brain of a freely behaving animal. This proposal seeks to overcome this challenge by accomplishing three Specific Aims: 1) To develop a miniature microdrive in which the intracellular electrode can be rapidly loaded and flexibly positioned over the brain surface. 2) To miniaturize the size and mass of the drive so that a mouse can readily carry at least two devices, facilitating an assessment of functional connectivity between neurons and brain areas. 3) To make intracelular recordings in the auditory cortex of freely behaving mice as they process auditory stimuli in conditions that are known to strongly modulate auditory responses. The refinement of this technology will be widely beneficial to the neuroscience community and its application in the mouse will open the door to analyzing how disordered neural activity underlies diseases. !