Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2016

Open Access 01-12-2016 | Research

Thalamocortical-auditory network alterations following cuprizone‐induced demyelination

Authors: Nikoo Ghaffarian, Masoud Mesgari, Manuela Cerina, Kerstin Göbel, Thomas Budde, Erwin-Josef Speckmann, Sven G. Meuth, Ali Gorji

Published in: Journal of Neuroinflammation | Issue 1/2016

Login to get access

Abstract

Background

Demyelination and remyelination are common pathological processes in many neurological disorders, including multiple sclerosis (MS). Clinical evidence suggests extensive involvement of the thalamocortical (TC) system in patients suffering from MS.

Methods

Using murine brain slices of the primary auditory cortex, we investigated the functional consequences of cuprizone-induced de- and remyelination on neuronal activity and auditory TC synaptic transmission in vitro.

Results

Our results revealed an impact of myelin loss and restoration on intrinsic cellular firing patterns, synaptic transmission, and neuronal plasticity in layer 3 and 4 neurons of the auditory TC network. While there was a complex hyper- and depolarizing shift of the resting membrane potential, spontaneous and induced action potential firing was reduced during demyelination and early remyelination. In addition, excitatory postsynaptic potential amplitudes were decreased and induction of LTP was reduced during demyelination.

Conclusions

These data indicate that demyelination-induced impairment of neurons and network activity within the TC system may underlie clinical symptoms observed in demyelinating diseases, corroborating human findings that disease progression is significantly correlated with microstructural tissue damage of the TC system. Further investigation into focal inflammation-induced demyelination models ex vivo and in vivo are needed to understand the functional implication of local and remote lesion formation on TC network activity in MS.
Literature
1.
Lassmann H, Bruck W, Lucchinetti CF. The immunopathology of multiple sclerosis: an overview. Brain Pathol. 2007;17:210–8.CrossRefPubMed
2.
Duncan ID, Brower A, Kondo Y, Curlee Jr JF, Schultz RD. Extensive remyelination of the CNS leads to functional recovery. Proc Natl Acad Sci U S A. 2009;106:6832–6.CrossRefPubMedPubMedCentral
3.
Fields RD. A new mechanism of nervous system plasticity: activity-dependent myelination. Nat Rev Neurosci. 2015;16:756–67.CrossRefPubMed
4.
Rasminsky M, Kearney RE, Aguayo AJ, Bray GM. Conduction of nervous impulses in spinal roots and peripheral nerves of dystrophic mice. Brain Res. 1978;143:71–85.CrossRefPubMed
5.
Felts PA, Kapoor R, Smith KJ. A mechanism for ectopic firing in central demyelinated axons. Brain. 1995;118:1225–31.CrossRefPubMed
6.
Kapoor R, Li YG, Smith KJ. Slow sodium-dependent potential oscillations contribute to ectopic firing in mammalian demyelinated axons. Brain. 1997;120:647–52.CrossRefPubMed
7.
Hamada MS, Kole MH. Myelin loss and axonal ion channel adaptations associated with gray matter neuronal hyperexcitability. J Neurosci. 2015;35:7272–86.CrossRefPubMedPubMedCentral
8.
Mori F, Kusayanagi H, Buttari F, Centini B, Monteleone F, Nicoletti CG, Bernardi G, Di Cantogno EV, Marciani MG, Centonze D. Early treatment with high-dose interferon beta-1a reverses cognitive and cortical plasticity deficits in multiple sclerosis. Funct Neurol. 2012;27:163–8.PubMed
9.
Kim do Y, Hao J, Liu R, Turner G, Shi FD, Rho JM. Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis. PLoS ONE. 2012;7:e35476.CrossRefPubMed
10.
Mori F, Kusayanagi H, Nicoletti CG, Weiss S, Marciani MG, Centonze D. Cortical plasticity predicts recovery from relapse in multiple sclerosis. Mult Scler. 2014;20:451–7.CrossRefPubMed
11.
Liu X, Basavaraj S, Krishnan R, Yan J. Contributions of the thalamocortical system towards sound-specific auditory plasticity. Neurosci Biobehav Rev. 2011;35:2155–61.CrossRefPubMed
12.
O’Muircheartaigh J, Vollmar C, Barker GJ, Kumari V, Symms MR, Thompson P, Duncan JS, Koepp MJ, Richardson MP. Abnormal thalamocortical structural and functional connectivity in juvenile myoclonic epilepsy. Brain. 2012;135:3635–44.CrossRefPubMedPubMedCentral
13.
Nair A, Treiber JM, Shukla DK, Shih P, Müller RA. Impaired thalamocortical connectivity in autism spectrum disorder: a study of functional and anatomical connectivity. Brain. 2013;136:1942–55.CrossRefPubMedPubMedCentral
14.
Moyer CE, Delevich KM, Fish KN, Asafu-Adjei JK, Sampson AR, Dorph-Petersen KA, Lewis DA, Sweet RA. Intracortical excitatory and thalamocortical boutons are intact in primary auditory cortex in schizophrenia. Schizophr Res. 2013;149:127–34.CrossRefPubMedPubMedCentral
15.
Minagar A, Barnett MH, Benedict RH, Pelletier D, Pirko I, Sahraian MA, Frohman E, Zivadinov R. The thalamus and multiple sclerosis: modern views on pathologic, imaging, and clinical aspects. Neurology. 2013;80:210–9.CrossRefPubMedPubMedCentral
16.
17.
Dell’Acqua ML, Landi D, Zito G, Zappasodi F, Lupoi D, Rossini PM, Filippi MM, Tecchio F. Thalamocortical sensorimotor circuit in multiple sclerosis: an integrated structural and electrophysiological assessment. Hum Brain Mapp. 2010;31:1588–600.CrossRefPubMed
18.
Bergamaschi R, Romani A, Zappoli F, Versino M, Cosi V. MRI and brainstem auditory evoked potential evidence of eighth cranial nerve involvement in multiple sclerosis. Neurology. 1997;48:270–2.CrossRefPubMed
19.
Kallmann BA, Fackelmann S, Toyka KV, Rieckmann P, Reiners K. Early abnormalities of evoked potentials and future disability in patients with multiple sclerosis. Mult Scler. 2006;12:58–65.CrossRefPubMed
20.
Matas CG, Matas SL, Oliveira CR, Gonçalves IC. Auditory evoked potentials and multiple sclerosis. Arq Neuropsiquiatr. 2010;68:528–34.CrossRefPubMed
21.
Vakilzadeh G, Khodagholi F, Ghadiri T, Darvishi M, Ghaemi A, Noorbakhsh F, Gorji A, Sharifzadeh M. Protective effect of a cAMP analogue on behavioral deficits and neuropathological changes in cuprizone model of demyelination. Mol Neurobiol. 2015;52:130–41.CrossRefPubMed
22.
Vakilzadeh G, Khodagholi F, Ghadiri T, Ghaemi A, Noorbakhsh F, Sharifzadeh M, Gorji A. The effect of melatonin on behavioral, molecular, and histopathological changes in cuprizone model of demyelination. Mol Neurobiol. 2015 Aug 27. [Epub ahead of print].
23.
Gudi V, Gingele S, Skripuletz T, Stangel M. Glial response during cuprizone-induced de- and remyelination in the CNS: lessons learned. Front Cell Neurosci. 2014;8:73.CrossRefPubMedPubMedCentral
24.
Skripuletz T, Gudi V, Hackstette D, Stangel M. De- and remyelination in the CNS white and grey matter induced by cuprizone: the old, the new, and the unexpected. Histol Histopathol. 2011;26:1585–97.PubMed
25.
Broicher T, Bidmon HJ, Kamuf B, Coulon P, Gorji A, Pape HC, Speckmann EJ, Budde T. Thalamic afferent activation of supragranular layers in auditory cortex in vitro: a voltage sensitive dye study. Neuroscience. 2010;165:371–85.CrossRefPubMed
26.
Ghadiri MK, Kozian M, Ghaffarian N, Stummer W, Kazemi H, Speckmann EJ, Gorji A. Sequential changes in neuronal activity in single neocortical neurons after spreading depression. Cephalalgia. 2012;32:116–24.CrossRefPubMed
27.
Mesgari M, Ghaffarian N, Khaleghi Ghadiri M, Sadeghian H, Speckmann EJ, Stummer W, Gorji A. Altered inhibition in the hippocampal neural networks after spreading depression. Neuroscience. 2015;304:190–7.CrossRefPubMed
28.
Anderson WW, Collingridge GL. Capabilities of the WinLTP data acquisition program extending beyond basic LTP experimental functions. J Neurosci Methods. 2007;162:346–56.CrossRefPubMed
29.
Skripuletz T, Lindner M, Kotsiari A, Garde N, Fokuhl J, Linsmeier F, Trebst C, Stangel M. Cortical demyelination is prominent in the murine cuprizone model and is strain-dependent. Am J Pathol. 2008;172:1053–61.CrossRefPubMedPubMedCentral
30.
Smith PH, Populin LC. Fundamental differences between the thalamocortical recipient layers of the cat auditory and visual cortices. J Comp Neurol. 2001;436:508–19.CrossRefPubMed
31.
32.
Kratz MB, Manis PB. Spatial organization of excitatory synaptic inputs to layer 4 neurons in mouse primary auditory cortex. Front Neural Circuits. 2015;9:17.CrossRefPubMedPubMedCentral
33.
Evangelou N, Konz D, Esiri MM, Smith S, Palace J, Matthews PM. Regional axonal loss in the corpus callosum correlates with cerebral white matter lesion volume and distribution in multiple sclerosis. Brain. 2000;123:1845–9.CrossRefPubMed
34.
Raybaud C. The corpus callosum, the other great forebrain commissures, and the septum pellucidum: anatomy, development, and malformation. Neuroradiology. 2010;52:447–77.CrossRefPubMed
35.
Steelman AJ, Thompson JP, Li J. Demyelination and remyelination in anatomically distinct regions of the corpus callosum following cuprizone intoxication. Neurosci Res. 2012;72:32–42.CrossRefPubMed
36.
Henry RG, Shieh M, Amirbekian B, Chung S, Okuda DT, Pelletier D. Connecting white matter injury and thalamic atrophy in clinically isolated syndromes. J Neurol Sci. 2009;282:61–6.CrossRefPubMed
37.
38.
Ojima H, Murakami K. Intracellular characterization of suppressive responses in supragranular pyramidal neurons of cat primary auditory cortex in vivo. Cereb Cortex. 2002;12:1079–91.CrossRefPubMed
39.
Tarczy-Hornoch K, Martin KAC, Jack JJB, Stratford KJ. Synaptic interactions between smooth and spiny neurones in layer 4 of cat visual cortex in vitro. J Physiol Lond. 1998;508:351–63.CrossRefPubMedPubMedCentral
40.
Helmstaedter M, Staiger JF, Sakmann B, Feldmeyer D. Efficient recruitment of layer 2/3 interneurons by layer 4 input in single columns of rat somatosensory cortex. J Neurosci. 2008;28:8273–84.CrossRefPubMed
41.
Pluta S, Naka A, Veit J, Telian G, Yao L, Hakim R, Taylor D, Adesnik H. A direct translaminar inhibitory circuit tunes cortical output. Nat Neurosci. 2015;18:1631–40.CrossRefPubMedPubMedCentral
42.
Bendfeldt K, Kappos L, Radue EW, Borgwardt S. Longitudinal spatiotemporal distribution of gray and white matter pathology in multiple sclerosis. AJNR Am J Neuroradiol. 2010;31:E45.CrossRefPubMed
43.
Tomassy GS, Berger DR, Chen HH, Kasthuri N, Hayworth KJ, Vercelli A, Seung HS, Lichtman JW, Arlotta P. Distinct profiles of myelin distribution along single axons of pyramidal neurons in the neocortex. Science. 2014;344:319–24.CrossRefPubMedPubMedCentral
44.
Tagge I, O’Connor A, Chaudhary P, Pollaro J, Berlow Y, Chalupsky M, Bourdette D, Woltjer R, Johnson M, Rooney W. Spatio-temporal patterns of demyelination and remyelination in the cuprizone mouse model. PLoS ONE. 2016;11:e0152480.CrossRefPubMedPubMedCentral
45.
Matsushima GK, Morell P. The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathol. 2001;11:107–16.CrossRefPubMed
46.
Hibbits N, Pannu R, Wu TJ, Armstrong RC. Cuprizone demyelination of the corpus callosum in mice correlates with altered social interaction and impaired bilateral sensorimotor coordination. ASN Neuro. 2009;1:153-164.
47.
Crawford DK, Mangiardi M, Xia X, López-Valdés HE, Tiwari-Woodruff SK. Functional recovery of callosal axons following demyelination: a critical window. Neuroscience. 2009;164:1407–21.CrossRefPubMed
48.
Bando Y, Takakusaki K, Ito S, Terayama R, Kashiwayanagi M, Yoshida S. Differential changes in axonal conduction following CNS demyelination in two mouse models. Eur J Neurosci. 2008;28:1731–42.CrossRefPubMed
49.
Smith PM, Jeffery ND. Histological and ultrastructural analysis of white matter damage after naturally-occurring spinal cord injury. Brain Pathol. 2006;16:99–109.CrossRefPubMed
50.
Gautier HO, Evans KA, Volbracht K, James R, Sitnikov S, Lundgaard I, James F, Lao-Peregrin C, Reynolds R, Franklin RJ, Káradóttir RT. Neuronal activity regulates remyelination via glutamate signalling to oligodendrocyte progenitors. Nat Commun. 2015;6:8518.CrossRefPubMedPubMedCentral
51.
Smith KJ. Sodium channels and multiple sclerosis: roles in symptom production, damage and therapy. Brain Pathol. 2007;17:230–42.CrossRefPubMed
52.
Rose HJ, Metherate R. Auditory thalamocortical transmission is reliable and temporally precise. J Neurophysiol. 2005;94:2019–30.CrossRefPubMed
53.
Wehr M, Zador AM. Synaptic mechanisms of forward suppression in rat auditory cortex. Neuron. 2005;47:437–45.CrossRefPubMed
54.
Di Filippo M, Chiasserini D, Gardoni F, Viviani B, Tozzi A, Giampà C, Costa C, Tantucci M, Zianni E, Boraso M, Siliquini S, de Iure A, Ghiglieri V, Colcelli E, Baker D, Sarchielli P, Fusco FR, Di Luca M, Calabresi P.. Effects of central and peripheral inflammation on hippocampal synaptic plasticity. Neurobiol Dis. 2013;52:229–36.CrossRefPubMed
55.
Novkovic T, Shchyglo O, Gold R, Manahan-Vaughan D. Hippocampal function is compromised in an animal model of multiple sclerosis. Neuroscience. 2015;309:100–12.CrossRefPubMed
56.
Prochnow N, Gold R, Haghikia A. An electrophysiologic approach to quantify impaired synaptic transmission and plasticity in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2013;264:48–53.CrossRefPubMed
57.
Weiss S, Mori F, Rossi S, Centonze D. Disability in multiple sclerosis: when synaptic long-term potentiation fails. Neurosci Biobehav Rev. 2014;43:88–99.CrossRefPubMed
Metadata
Title
Thalamocortical-auditory network alterations following cuprizone‐induced demyelination
Authors
Nikoo Ghaffarian
Masoud Mesgari
Manuela Cerina
Kerstin Göbel
Thomas Budde
Erwin-Josef Speckmann
Sven G. Meuth
Ali Gorji
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2016
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-016-0629-0

Other articles of this Issue 1/2016

Journal of Neuroinflammation 1/2016 Go to the issue

Research

A murine model of inflammation-induced cerebral microbleeds

Research

Characterization of a novel adult murine immortalized microglial cell line and its activation by amyloid-beta

Research

Chemokine CXCL13 mediates orofacial neuropathic pain via CXCR5/ERK pathway in the trigeminal ganglion of mice

Research

Characterization of the binding pattern of human aquaporin-4 autoantibodies in patients with neuromyelitis optica spectrum disorders

Research

The glucagon-like peptide-1 receptor agonist exendin-4 ameliorates warfarin-associated hemorrhagic transformation after cerebral ischemia

Research

Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke