Stüttgen Maik C, Nonkes Lourens J P, Geis H Rüdiger A P, Tiesinga Paul H, Houweling Arthur R
Department of Neuroscience, Erasmus University Medical Center, Rotterdam, The Netherlands;
Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
J Neurophysiol. 2017 Mar 1;117(3):1363-1378. doi: 10.1152/jn.00479.2016. Epub 2017 Jan 11.
Temporal patterns of action potentials influence a variety of activity-dependent intra- and intercellular processes and play an important role in theories of neural coding. Elucidating the mechanisms underlying these phenomena requires imposing spike trains with precisely defined patterns, but this has been challenging due to the limitations of existing stimulation techniques. Here we present a new nanostimulation method providing control over the action potential output of individual cortical neurons. Spikes are elicited through the juxtacellular application of short-duration fluctuating currents ("kurzpulses"), allowing for the sub-millisecond precise and reproducible induction of arbitrary patterns of action potentials at all physiologically relevant firing frequencies (<120 Hz), including minute-long spike trains recorded in freely moving animals. We systematically compared our method to whole cell current injection, as well as optogenetic stimulation, and show that nanostimulation performance compares favorably with these techniques. This new nanostimulation approach is easily applied, can be readily performed in awake behaving animals, and thus promises to be a powerful tool for systematic investigations into the temporal elements of neural codes, as well as the mechanisms underlying a wide variety of activity-dependent cellular processes. Assessing the impact of temporal features of neuronal spike trains requires imposing arbitrary patterns of spiking on individual neurons during behavior, but this has been difficult to achieve due to limitations of existing stimulation methods. We present a technique that overcomes these limitations by using carefully designed short-duration fluctuating juxtacellular current injections, which allow for the precise and reliable evocation of arbitrary patterns of neuronal spikes in single neurons in vivo.
动作电位的时间模式会影响多种与活动相关的细胞内和细胞间过程，并且在神经编码理论中发挥着重要作用。阐明这些现象背后的机制需要施加具有精确界定模式的尖峰序列，但由于现有刺激技术的局限性，这一直具有挑战性。在此，我们展示了一种新的纳米刺激方法，可对单个皮层神经元的动作电位输出进行控制。通过短持续时间波动电流（“短脉冲”）的近细胞施加来引发尖峰，从而能够在所有生理相关的放电频率（<120Hz）下，以亚毫秒级的精度和可重复性诱导任意模式的动作电位，包括在自由活动动物中记录的长达数分钟的尖峰序列。我们系统地将我们的方法与全细胞电流注入以及光遗传学刺激进行了比较，并表明纳米刺激性能与这些技术相比具有优势。这种新的纳米刺激方法易于应用，可以在清醒行为动物中轻松进行，因此有望成为系统研究神经编码的时间要素以及各种与活动相关的细胞过程背后机制的强大工具。评估神经元尖峰序列的时间特征的影响需要在行为期间对单个神经元施加任意的尖峰模式，但由于现有刺激方法的局限性，这一直难以实现。我们提出了一种技术，通过使用精心设计的短持续时间波动近细胞电流注入来克服这些局限性，该技术能够在体内单个神经元中精确且可靠地诱发任意模式的神经元尖峰。
