Williams Brice, Speed Anderson, Haider Bilal
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University , Atlanta, Georgia.
J Neurophysiol. 2018 Dec 1;120(6):2975-2987. doi: 10.1152/jn.00500.2018. Epub 2018 Sep 26.
The mouse has become an influential model system for investigating the mammalian nervous system. Technologies in mice enable recording and manipulation of neural circuits during tasks where they respond to sensory stimuli by licking for liquid rewards. Precise monitoring of licking during these tasks provides an accessible metric of sensory-motor processing, particularly when combined with simultaneous neural recordings. There are several challenges in designing and implementing lick detectors during head-fixed neurophysiological experiments in mice. First, mice are small, and licking behaviors are easily perturbed or biased by large sensors. Second, neural recordings during licking are highly sensitive to electrical contact artifacts. Third, submillisecond lick detection latencies are required to generate control signals that manipulate neural activity at appropriate time scales. Here we designed, characterized, and implemented a contactless dual-port device that precisely measures directional licking in head-fixed mice performing visual behavior. We first determined the optimal characteristics of our detector through design iteration and then quantified device performance under ideal conditions. We then tested performance during head-fixed mouse behavior with simultaneous neural recordings in vivo. We finally demonstrate our device's ability to detect directional licks and generate appropriate control signals in real time to rapidly suppress licking behavior via closed-loop inhibition of neural activity. Our dual-port detector is cost effective and easily replicable, and it should enable a wide variety of applications probing the neural circuit basis of sensory perception, motor action, and learning in normal and transgenic mouse models. NEW & NOTEWORTHY Mice readily learn tasks in which they respond to sensory cues by licking for liquid rewards; tasks that involve multiple licking responses allow study of neural circuits underlying decision making and sensory-motor integration. Here we design, characterize, and implement a novel dual-port lick detector that precisely measures directional licking in head-fixed mice performing visual behavior, enabling simultaneous neural recording and closed-loop manipulation of licking.
小鼠已成为研究哺乳动物神经系统的一个有影响力的模型系统。小鼠相关技术能够在小鼠通过舔舐获取液体奖励以响应感觉刺激的任务过程中，对神经回路进行记录和操纵。在这些任务中对舔舐行为进行精确监测，可提供一个易于获取的感觉运动处理指标，尤其是当与同步神经记录相结合时。在设计和实施用于小鼠头部固定神经生理学实验的舔舐探测器时，存在几个挑战。首先，小鼠体型小，舔舐行为很容易受到大型传感器的干扰或偏差影响。其次，舔舐过程中的神经记录对电接触伪迹高度敏感。第三，需要亚毫秒级的舔舐检测延迟来生成在适当时间尺度上操纵神经活动的控制信号。在此，我们设计、表征并实现了一种非接触式双端口设备，该设备可精确测量进行视觉行为的头部固定小鼠的定向舔舐。我们首先通过设计迭代确定了探测器的最佳特性，然后在理想条件下量化了设备性能。接着，我们在体内同步神经记录的头部固定小鼠行为过程中测试了性能。我们最终展示了我们的设备检测定向舔舐并实时生成适当控制信号以通过神经活动的闭环抑制快速抑制舔舐行为的能力。我们的双端口探测器具有成本效益且易于复制，它应该能够在正常和转基因小鼠模型中实现广泛的应用，以探究感觉感知神经回路基础、运动行为以及学习过程。新内容与值得关注之处：小鼠很容易学会通过舔舐获取液体奖励来响应感觉线索的任务；涉及多个舔舐反应的任务允许研究决策和感觉运动整合背后的神经回路。在此，我们设计、表征并实现了一种新型双端口舔舐探测器，该探测器可精确测量进行视觉行为地头部固定小鼠的定向舔舐，从而实现对舔舐行为的同步神经记录和闭环操纵。
