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Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro

Journal article
Authors Marta Perez-Alcazar
Georgia Culley
Tim Lyckenvik
Kristoffer Mobarrez
Andreas Björefeldt
Pontus Wasling
Henrik Seth
Fredrik Asztely
A. Harrer
B. Iglseder
L. Aigner
Eric Hanse
Sebastian Illes
Published in Frontiers in Cellular Neuroscience
Volume 10
ISSN 1662-5102
Publication year 2016
Published at Institute of Neuroscience and Physiology
Language en
Links dx.doi.org/10.3389/fncel.2016.00054
Keywords human cerebrospinal fluid, hippocampal neuronal function, hippocampal neuronal survival, alzheimers-disease, organotypic cultures, brain, model, csf, Neurosciences & Neurology
Subject categories Neurosciences, Neurology

Abstract

For decades it has been hypothesized that molecules within the cerebrospinal fluid (CSF) diffuse into the brain parenchyma and influence the function of neurons. However, the functional consequences of CSF on neuronal circuits are largely unexplored and unknown. A major reason for this is the absence of appropriate neuronal in vitro model systems, and it is uncertain if neurons cultured in pure CSF survive and preserve electrophysiological functionality in vitro. In this article, we present an approach to address how human CSF (hCSF) influences neuronal circuits in vitro. We validate our approach by comparing the morphology, viability, and electrophysiological function of single neurons and at the network level in rat organotypic slice and primary neuronal cultures cultivated either in hCSF or in defined standard culture media. Our results demonstrate that rodent hippocampal slices and primary neurons cultured in hCSF maintain neuronal morphology and preserve synaptic transmission. Importantly, we show that hCSF increases neuronal viability and the number of electrophysiologically active neurons in comparison to the culture media. In summary, our data indicate that hCSF represents a physiological environment for neurons in vitro and a superior culture condition compared to the defined standard media. Moreover, this experimental approach paves the way to assess the functional consequences of CSF on neuronal circuits as well as suggesting a novel strategy for central nervous system (CNS) disease modeling.

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