[en] Peripheral inflammation is known to impact brain function, resulting in lethargy, loss of appetite and impaired cognitive abilities. However, the channels for information transfer from the periphery to the brain, the corresponding signaling molecules and the inflammation-induced interaction between microglia and neurons remain obscure. Here, we used longitudinal in vivo two-photon Ca2+ imaging to monitor neuronal activity in the mouse cortex throughout the early (initiation) and late (resolution) phases of peripheral inflammation. Single peripheral lipopolysaccharide injection induced a substantial but transient increase in ongoing neuronal activity, restricted to the initiation phase, whereas the impairment of visual processing was selectively observed during the resolution phase of systemic inflammation. In the frontal/motor cortex, the initiation phase-specific cortical hyperactivity was seen in the deep (layer 5) and superficial (layer 2/3) pyramidal neurons but not in the axons coming from the somatosensory cortex, and was accompanied by reduced activity of layer 2/3 cortical interneurons. Moreover, the hyperactivity was preserved after depletion of microglia and in NLRP3-/- mice but absent in TNF-α-/- mice. Together, these data identify microglia-independent and TNF-α-mediated reduction of cortical inhibition as a likely cause of the initiation phase-specific cortical hyperactivity and reveal the resolution phase-specific impairment of sensory processing, presumably caused by activated microglia.
Disciplines :
Neurology
Author, co-author :
Odoj, Karin; Institute of Physiology, Department of Neurophysiology, Eberhard Karls University Tübingen, Tübingen, Germany
Brawek, Bianca; Institute of Physiology, Department of Neurophysiology, Eberhard Karls University Tübingen, Tübingen, Germany
Asavapanumas, Nithi; Institute of Physiology, Department of Neurophysiology, Eberhard Karls University Tübingen, Tübingen, Germany
Mojtahedi, Nima; Institute of Physiology, Department of Neurophysiology, Eberhard Karls University Tübingen, Tübingen, Germany
HENEKA, Michael ; Department of Neurodegenerative Disease and Geriatric Psychiatry, University of Bonn, Bonn, Germany, German Center for Neurodegenerative Diseases, Bonn, Germany
Garaschuk, Olga; Institute of Physiology, Department of Neurophysiology, Eberhard Karls University Tübingen, Tübingen, Germany. Electronic address: olga.garaschuk@uni-tuebingen.de
External co-authors :
yes
Language :
English
Title :
In vivo mechanisms of cortical network dysfunction induced by systemic inflammation.
We thank E. Zirdum, A. Weible, and K. Schöntag for technical assistance and Y. Kovalchuk for experimental help during the revision of this study. This work was partially supported by the DFG grant GA 654/13-1 to O.G. PLX 5622 drug was provided by Plexxikon Inc. under Material Transfer Agreement.
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