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ORIGINAL RESEARCH article

Front. Cell. Neurosci.
Sec. Cellular Neurophysiology
Volume 18 - 2024 | doi: 10.3389/fncel.2024.1410275
This article is part of the Research Topic Glial Cells in Health and Disease: Impacts on Neural Circuits and Plasticity View all 6 articles

Ammonium chloride reduces excitatory synaptic transmission onto CA1 pyramidal neurons of mouse organotypic slice cultures

Provisionally accepted
Dimitrios Kleidonas Dimitrios Kleidonas 1Maximilian Lenz Maximilian Lenz 1Dieter Häussinger Dieter Häussinger 2Andreas Vlachos Andreas Vlachos 3,4,5*
  • 1 Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  • 2 Heinrich Heine University Düsseldorf, Düsseldorf, Germany
  • 3 Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany, Freiburg, Germany
  • 4 Center BrainLinks-BrainTools, University of Freiburg, Freiburg, Germany
  • 5 Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany

The final, formatted version of the article will be published soon.

    Acute liver dysfunction commonly leads to rapid increases in ammonia concentrations in both the serum and the cerebrospinal fluid. These elevations primarily affect brain astrocytes, causing modifications in their structure and function. However, its impact on neurons is not yet fully understood. In this study, we investigated the impact of elevated ammonium chloride levels (NH4Cl, 5 mM) on synaptic transmission onto CA1 pyramidal neurons in mouse organotypic entorhino-hippocampal tissue cultures. We found that acute exposure to NH4Cl reversibly attenuated excitatory synaptic transmission and affected CA3-CA1 synapses.Notably, NH4Cl modified astrocytic, but not CA1 pyramidal neuron, passive intrinsic properties.To further explore the role of astrocytes in NH4Cl-induced attenuation of synaptic transmission, we used methionine sulfoximine to target glutamine synthetase, a key astrocytic enzyme for ammonia clearance in the central nervous system. Inhibition of glutamine synthetase effectively prevented the downregulation of excitatory synaptic activity decrease, underscoring the significant role of astrocytes in adjusting excitatory synapses during acute ammonia elevation.

    Keywords: Ammonium Chloride, excitatory neurotransmission, Astrocytes, glutamine synthetase, CA1

    Received: 31 Mar 2024; Accepted: 03 Sep 2024.

    Copyright: © 2024 Kleidonas, Lenz, Häussinger and Vlachos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Andreas Vlachos, Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany, Freiburg, Germany

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