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Neuromodulation of fast-spiking and non-fast-spiking hippocampal CA1 interneurons by human cerebrospinal fluid.

Journal article
Authors Andreas Björefeldt
Pontus Wasling
Henrik Zetterberg
Eric Hanse
Published in The Journal of physiology
Volume 594
Issue 4
Pages 937-52
ISSN 1469-7793
Publication year 2016
Published at Institute of Neuroscience and Physiology, Department of Physiology
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 937-52
Language en
Subject categories Neurochemistry


GABAergic interneurons intricately regulate the activity of hippocampal and neocortical networks. Their function in vivo is likely to be tuned by neuromodulatory substances in brain extracellular fluid. However, in vitro investigations of GABAergic interneuron function do not account for such effects, as neurons are kept in artificial extracellular fluid. To examine the neuromodulatory influence of brain extracellular fluid on GABAergic activity, we recorded from fast-spiking and non-fast-spiking CA1 interneurons, as well as from pyramidal cells, in the presence of human cerebrospinal fluid (hCSF), using a matched artificial cerebrospinal (aCSF) fluid as control. We found that hCSF increased the frequency of spontaneous firing more than twofold in the two groups of interneurons, and more than fourfold in CA1 pyramidal cells. hCSF did not affect the resting membrane potential of CA1 interneurons but caused depolarization in pyramidal cells. The increased excitability of interneurons and pyramidal cells was accompanied by reductions in afterhyperpolarization amplitudes and a left-shift in the frequency-current relationships. Our results suggest that ambient concentrations of neuromodulators in the brain extracellular fluid powerfully influence the excitability of neuronal networks. This article is protected by copyright. All rights reserved.

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