Department of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Department of Neuroscience, Brown University, Providence, Rhode Island.
Hippocampus. 2020 Feb;30(2):101-113. doi: 10.1002/hipo.23135. Epub 2019 Jul 17.
Gamma oscillations (30-80 Hz) are fast network activity patterns frequently linked to cognition. They are commonly studied in hippocampal brain slices in vitro, where they can be evoked via pharmacological activation of various receptor families. One limitation of this approach is that neuronal activity is studied in a highly artificial extracellular fluid environment, as provided by artificial cerebrospinal fluid (aCSF). Here, we examine the influence of human cerebrospinal fluid (hCSF) on kainate-evoked and spontaneous gamma oscillations in mouse hippocampus. We show that hCSF, as compared to aCSF of matched electrolyte and glucose composition, increases the power of kainate-evoked gamma oscillations and induces spontaneous gamma activity in areas CA3 and CA1 that is reversed by washout. Bath application of atropine entirely abolished hCSF-induced gamma oscillations, indicating critical contribution from muscarinic acetylcholine receptor-mediated signaling. In separate whole-cell patch clamp recordings from rat hippocampus, hCSF increased theta resonance frequency and strength in pyramidal cells along with enhancement of h-current (I ) amplitude. We found no evidence of intrinsic gamma frequency resonance at baseline (aCSF) among fast-spiking interneurons, and this was not altered by hCSF. However, hCSF increased the excitability of fast-spiking interneurons, which likely contributed to gamma rhythmogenesis. Our findings show that hCSF promotes network gamma oscillations in the hippocampus in vitro and suggest that neuromodulators distributed in CSF could have significant influence on neuronal network activity in vivo.
伽马振荡（30-80 Hz）是一种快速的网络活动模式，通常与认知有关。它们在体外海马脑片中经常被研究，通过药理学激活各种受体家族来诱发。这种方法的一个局限性是，神经元活动是在高度人工的细胞外液环境中研究的，这种环境由人工脑脊液（aCSF）提供。在这里，我们研究了人脑脊液（hCSF）对小鼠海马中海马刀氨酸诱发和自发伽马振荡的影响。我们发现，与具有匹配电解质和葡萄糖组成的 aCSF 相比，hCSF 增加了刀氨酸诱发的伽马振荡的功率，并在 CA3 和 CA1 区诱导自发的伽马活动，这种活动可以通过冲洗来逆转。灌流应用阿托品完全消除了 hCSF 诱导的伽马振荡，表明其来源于毒蕈碱乙酰胆碱受体介导的信号转导。在来自大鼠海马的单独全细胞贴片记录中，hCSF 增加了锥体细胞中的θ共振频率和强度，同时增强了 h 电流（I ）的幅度。我们没有发现在基线（aCSF）时快突细胞固有伽马频率共振的证据，hCSF 也没有改变这一点。然而，hCSF 增加了快突细胞的兴奋性，这可能有助于产生伽马节律。我们的研究结果表明，hCSF 在体外促进海马中的网络伽马振荡，并表明分布在 CSF 中的神经调质可能对体内神经元网络活动产生重大影响。
