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Human cerebrospinal fluid promotes spontaneous gamma oscillations in the hippocampus in vitro

Journal article
Authors Andreas Björefeldt
F. Roshan
My Forsberg
Henrik Zetterberg
Eric Hanse
A. Fisahn
Published in Hippocampus
ISSN 1050-9631
Publication year 2019
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Physiology
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Language en
Keywords CSF, fast-spiking interneuron, hippocampal brain slice, neuromodulation, pyramidal cell, action-potential desynchronization, fast network oscillations, fast-spiking, receptor activation, feedback inhibition, gabaergic, neurons, pyramidal neurons, rhythmic activity, h-current, interneurons, Neurosciences & Neurology
Subject categories Neurosciences


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-h) 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.

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