Behavioral Paradigm for the Evaluation of Stimulation-Evoked Somatosensory Perception Thresholds in Rats.
Behavioral Paradigm for the Evaluation of Stimulation-Evoked Somatosensory Perception Thresholds in Rats.
复制标题
评估大鼠刺激诱发体感知觉阈值的行为范式。
DOI：
10.1101/2023.05.04.537848
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Hernandez-Reynoso,AnaG
中科院分区：
文献类型：
--
作者：
Smith,ThomasJ;Wu,Yupeng;Cheon,Claire;Khan,ArlinA;Srinivasan,Hari;Capadona,JeffreyR;Cogan,StuartF;Pancrazio,JosephJ;Engineer,CrystalT;Hernandez-Reynoso,AnaG
通过穿透性微电极阵列(MEAs)对躯体感觉皮层进行皮质内微刺激(ICMS)可以唤起皮肤和本体感觉，从而恢复脊髓损伤患者的知觉。然而，在植入后，唤起这些感官知觉所需的ICMS电流幅度往往会随着时间的推移而变化。动物模型已被用来研究这些变化发生的机制，并帮助开发新的工程策略来缓解这些变化。非人灵长类动物通常是研究ICMS的首选动物，但关于它们的使用存在伦理问题。啮齿动物因其可获得性、可负担性和易操纵性而成为首选的动物模型，但用于研究ICMS的行为任务选择有限。在这项研究中，我们研究了一种创新的行为GO/NO-GO范式的应用，该范式能够在自由活动的大鼠中估计ICMS诱发的感觉知觉阈值。我们将动物分为两组，一组接受ICMS，另一组接受听觉音调。然后，我们训练动物按照ICMS电流控制的脉冲序列或频率控制的听觉音调进行鼻子戳--这是大鼠的一项公认的行为任务。当正确地戳鼻子时，动物会得到糖丸奖励。当不正确地戳鼻子时，动物会被轻轻吹一口气。在动物熟练地完成这项任务后，根据准确度、精密度和其他性能指标的定义，它们继续进行下一阶段的感知阈值检测，在这一阶段，我们使用改进的阶梯法改变ICMS幅度。最后，我们使用非线性回归来估计感知阈值。结果表明，我们的行为方案可以基于大鼠对条件刺激的鼻戳反应~95%的准确率来估计ICMS感知阈值。这一行为范式为评估刺激诱发的大鼠体感知觉提供了一种可靠的方法，可与听觉知觉评估相媲美。在未来的研究中，这种有效的方法可以用来研究新的MEA设备技术在ICMS诱发的感觉阈值稳定性方面的性能，使用自由运动的大鼠，或者研究与感觉识别相关的神经回路中的信息处理原理。
Intracortical microstimulation (ICMS) of the somatosensory cortex via penetrating microelectrode arrays (MEAs) can evoke cutaneous and proprioceptive sensations for restoration of perception in individuals with spinal cord injuries. However, ICMS current amplitudes needed to evoke these sensory percepts tend to change over time following implantation. Animal models have been used to investigate the mechanisms by which these changes occur and aid in the development of new engineering strategies to mitigate such changes. Non-human primates are commonly the animal of choice for investigating ICMS, but ethical concerns exist regarding their use. Rodents are a preferred animal model due to their availability, affordability, and ease of handling, but there are limited choices of behavioral tasks for investigating ICMS. In this study, we investigated the application of an innovative behavioral go/no-go paradigm capable of estimating ICMS-evoked sensory perception thresholds in freely moving rats. We divided animals into two groups, one receiving ICMS and a control group receiving auditory tones. Then, we trained the animals to nose-poke – a well-established behavioral task for rats – following either a suprathreshold ICMS current-controlled pulse train or frequency-controlled auditory tone. Animals received a sugar pellet reward when nose-poking correctly. When nose-poking incorrectly, animals received a mild air puff. After animals became proficient in this task, as defined by accuracy, precision, and other performance metrics, they continued to the next phase for perception threshold detection, where we varied the ICMS amplitude using a modified staircase method. Finally, we used non-linear regression to estimate perception thresholds. Results indicated that our behavioral protocol could estimate ICMS perception thresholds based on ~95% accuracy of rat nose-poke responses to the conditioned stimulus. This behavioral paradigm provides a robust methodology for evaluating stimulation-evoked somatosensory percepts in rats comparable to the evaluation of auditory percepts. In future studies, this validated methodology can be used to study the performance of novel MEA device technologies on ICMS-evoked perception threshold stability using freely moving rats or to investigate information processing principles in neural circuits related to sensory perception discrimination.