Turecek Josef, Han Victor Z, Cuzon Carlson Verginia C, Grant Kathleen A, Welsh John P
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98101.
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98101.
J Neurosci. 2016 Jun 15;36(24):6497-502. doi: 10.1523/JNEUROSCI.4495-15.2016.
Inferior olive (IO) neurons are critical for motor coordination and exhibit oscillations in membrane potential that are subthreshold for spiking. The prevalence, coherence, and continuity of those subthreshold oscillations (STOs) depend upon resonant interactions between neighboring neurons supported by electrical coupling. Many studies of the olivocerebellar system in rodents, in which STOs were related to tremor, whisking, and licking, fueled a debate over whether IO STOs were relevant for primates whose repertoire of movement is generally less periodic. The debate was never well informed due to the lack of a direct examination of the physiological properties of primate IO neurons. Here, we obtained dual patch-clamp recordings of neighboring IO neurons from young adult macaques in brainstem slices and compared them to identical recordings from rats. Macaque IO neurons exhibited an equivalent prevalence of continuous STOs as rats (45 vs 54%, respectively). However, macaque STOs were slower (1-4 Hz) and did not overlap with the dominant 4-9 Hz frequency of rats. The slower STO frequency of macaques was at least partially due to a prolonged membrane time constant and increased membrane capacitance that could be attributed to stronger electrical coupling and greater total dendritic length. The presence of synchronized STOs in the IO of adult macaques, coincident with strong and prevalent electrical coupling, answers a fundamental outstanding question in cerebellar neuroscience and is consistent with a prominent role for synchronized oscillation in primate sensory-motor control.
It was debated whether inferior olive (IO) neurons of primates behave as synchronized oscillators as was found for rodents using intracellular, optical, and multielectrode recordings. An inability to resolve this issue using single-Purkinje cell extracellular recordings in monkeys limited our understanding of timing mechanisms in the primate brain. Using dual whole-cell recordings from the IO of young adult rhesus macaques in acutely prepared brainstem slices, our work demonstrates that pairs of primate IO neurons show synchronized oscillations in membrane potential. The findings have strong mechanistic and translational relevance, as IO activation has been implicated in humans' perceptual timing of sensory events and motricity.
下橄榄核（IO）神经元对运动协调至关重要，其膜电位会出现低于动作电位阈值的振荡。这些阈下振荡（STOs）的发生率、相干性和连续性取决于电耦合所支持的相邻神经元之间的共振相互作用。在啮齿动物的橄榄小脑系统中，许多关于STOs与震颤、轻拂和舔舐相关的研究引发了一场争论，即IO STOs是否与灵长类动物相关，因为灵长类动物的运动模式通常周期性较弱。由于缺乏对灵长类动物IO神经元生理特性的确切研究，这场争论一直缺乏充分依据。在此，我们在脑干切片中对成年猕猴的相邻IO神经元进行了双膜片钳记录，并将其与大鼠的相同记录进行比较。猕猴IO神经元连续STOs的发生率与大鼠相当（分别为45%和54%）。然而，猕猴的STOs速度较慢（1 - 4赫兹），且与大鼠占主导的4 - 9赫兹频率不重叠。猕猴较慢的STO频率至少部分归因于膜时间常数延长和膜电容增加，这可能是由于更强的电耦合和更长的总树突长度所致。成年猕猴IO中同步STOs的存在，与强且普遍的电耦合相一致，回答了小脑神经科学中一个基本的悬而未决的问题，并且与同步振荡在灵长类动物感觉运动控制中的重要作用相符。
关于灵长类动物的下橄榄核（IO）神经元是否像在啮齿动物中通过细胞内、光学和多电极记录所发现的那样表现为同步振荡器，一直存在争论。在猴子中无法通过单浦肯野细胞胞外记录解决这个问题，限制了我们对灵长类动物大脑时间机制的理解。通过在急性制备的脑干切片中对成年恒河猴的IO进行双全细胞记录，我们的研究表明，成对的灵长类IO神经元在膜电位上表现出同步振荡。这些发现具有很强的机制和转化相关性，因为IO的激活与人类对感觉事件和运动能力的感知时间有关。
