Untethered high channel count electrophysiology for freely-moving animals

项目摘要 以单神经元分辨率和毫秒级时间尺度精度记录全脑活动对于 了解单个细胞和复杂的神经回路如何在时间和空间中相互作用。同时 需要记录和刺激分布在整个大脑中的大量神经元， 严格评估哺乳动物细胞水平上的神经计算理论， 需要记录来建立神经元回路/动力学的一般原理，以及神经元回路/动力学的复杂程度。 神经元活动与行为有关，这不仅有助于我们对大脑的基本理解， 神经和精神疾病的表面潜在原因，如阿尔茨海默氏症，帕金森氏症，TBI， 癫痫和抑郁症，并帮助开发新的和更有效的治疗方法。 这些是BRAIN计划的关键目标，也是LeafLabs的杨柳背后的驱动力， 电生理学记录系统，旨在利用新颖的，紧密包装的1000通道硅 探针最初由麻省理工学院的合成神经生物学小组开发。这些超高通道数 探针允许同时记录更多的神经元，开辟了科学探究的新途径， 电极的密集堆积允许神经元的空间过采样，允许自动尖峰脉冲， 分类技术，大大提高了跟踪单个单元的能力。 此外，LeafLabs的Catkin是一种定制的1000通道神经传感IC芯片（滤波、放大、多路复用， 和模数转换）已经被开发成与这些探头集成， 适合于在自由移动的电生理学实验中使用的探针/头台组合， 重量和成本都是市售云台的10倍。目前，The Catkin 探头/头台组合体通过一根超薄轻质电缆（单根）连接到杨柳DAQ系统 屏蔽的32 AWG双绞线），使系统成为许多长时间自由移动实验的理想选择。 然而，在某些行为设置中，即使是重量轻、极简的电缆也是不可取的。比如说， 因为高数据速率与用于管理电缆系绳的方法不兼容 （解缠器），研究人员必须偶尔进行干预，以解开电缆;或者，系绳的存在可能 导致动物行为的改变。为了满足这些需求，本申请提出开发 首个完全不受束缚的1000通道同步30 kHz体内电生理 记录模块，可作为一个轻量级的附加到现有的杨柳系统。

PROJECT SUMMARY Recording whole-brain activity with single neuron resolution and millisecond timescale precision is crucial to understanding how individual cells and complex neural circuits interact in both time and space. Simultaneous recording and stimulation of large populations of neurons distributed throughout the brain are needed to rigorously evaluate theories of neural computation at the cellular level in mammals, and extended longitudinal recordings are required to establish general principles for neuronal circuits/dynamics and how complex neuronal activity relates to behavior, both to further our fundamental understanding of the brain, but also to surface underlying causes of neurological and psychiatric conditions such as Alzheimer’s, Parkinson’s, TBI, epilepsy, and depression, and to aid development of novel and more effective treatments. These are key goals of the BRAIN initiative, and the driving force behind LeafLabs' Willow, an electrophysiology recording system designed to take advantage of novel, close-packed 1000-channel silicon probes originally developed by the Synthetic Neurobiology Group at MIT. These ultra-high-channel-count probes allow for more neurons to be recorded simultaneously, opening up new lines of scientific inquiry, and the dense packing of the electrodes permits spatial oversampling of the neurons, allowing for automated spike sorting techniques with greatly increased capability for tracking individual units. Additionally, LeafLabs' Catkin, a custom 1000 channel neurosensing IC chip (filter, amplification, multiplexing, and analog-digital conversion) has been developed to integrate with these probes, resulting in a probe/headstage combo suitable for use in freely-moving electrophysiology experiments that reduces size, weight, and cost each by a factor of 10 compared to commercially available headstages. Currently, the Catkin probe/headstage combo is tethered to the Willow DAQ system by an ultra thin and lightweight cable (a single shielded 32 AWG twisted pair), resulting in a system ideal for many prolonged freely moving experiments. However, in certain behavioral setups, even a lightweight, minimalist cable is undesirable. For example, because the high data rates are incompatible with approaches used to manage the cable tether (commutators), researchers must occasionally intervene to de-tangle cables; or, the presence of a tether may result in altered behavior from animals. To address these needs, this application proposes the development of a first-of-its-kind fully untethered 1000-channel-simultaneous 30kHz in-vivo electrophysiological recording module, to be made available as a lightweight add-on to the extant Willow system.