Contributions
Abstract: P568
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Neurophysiology
Background: Pathophysiologic myelin loss is an event common to many neurodegenerative diseases like multiple sclerosis (MS). In many animal models of MS and patients such event was often associated to the appearance of cognitive deficits.
Objectives: Since myelin loss alone could not mediate alteration of higher cortical functionality such as cognition and learning, we hypothesized that altered cortical neuronal network mechanisms could be altered following de- and remyelination.
Methods: We investigated the auditory thalamocortical (TC) system as exemplary neuronal network composed of both white and grey matter regions. We used the cuprizone model of general demyelination to assess alterations of the primary auditory cortex (A1; n = 11). Taking advantage of the spontaneous remyelination occurring in this model upon suspending cuprizone administration we assessed the potential benefits of myelin re-gain by combining voltage sensitive dye imaging techniques, extracellular recordings and behavior.
Results: Decreased neuronal network activation was observed following demyelination in all cortical layers (-65.8 % vs. control) accompanied by increased latency to response (8.9 ms vs. 12.4 ± 0.06 ms). Heat maps showed a transitory hyperexcitation during the early remyelination phase (7 days) associated to altered spreading of the incoming cortical information into A1. Further analysis of the hierarchical activation of the different cortical layers revealed that a delayed activation of the cortical interneurons in layer 4 (0.005 ms longer than control) could mediate the hyperexcitation and the altered spreading of activity. Demyelination was also associated with a permanent loss of the tonotopic cortical organization in vivo, and the inability to induce tone-frequency-dependent conditioned behaviors, a status persistent after full remyelination (25 days).
Conclusions: Demyelination altered the functionality of auditory neuronal networks and the persistency of alterations would indicate that despite myelin re-growth was necessary but not sufficient to ameliorate an irreversibly compromised network. Moreover, the molecular mechanisms underlying the hyperexcitation observed during the early phase of remyelination should be further investigated given the effect of a prolonged higher excitability of neurons.
Disclosure: This study was supported by the DFG CRC TRG128 -B06
Manuela Cerina: nothing to disclose
Venu Narayanan: nothing to disclose
Patrick Meuth: nothing to disclose
Kerstin Göbel: nothing to disclose
Alexander M. Herrmann: nothing to disclose
Stephanie Graebenitz: nothing to disclose
Thiemo Daldrup: nothing to disclose
Thomas Seidenbecher: nothing to disclose
Heinz Wiendl: nothing to disclose
Erwin J. Speckmann: nothing to disclose
Hans-Christian Pape: nothing to disclose
Sven G. Meuth: nothing to disclose
Thomas Budde: nothing to disclose
Abstract: P568
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Neurophysiology
Background: Pathophysiologic myelin loss is an event common to many neurodegenerative diseases like multiple sclerosis (MS). In many animal models of MS and patients such event was often associated to the appearance of cognitive deficits.
Objectives: Since myelin loss alone could not mediate alteration of higher cortical functionality such as cognition and learning, we hypothesized that altered cortical neuronal network mechanisms could be altered following de- and remyelination.
Methods: We investigated the auditory thalamocortical (TC) system as exemplary neuronal network composed of both white and grey matter regions. We used the cuprizone model of general demyelination to assess alterations of the primary auditory cortex (A1; n = 11). Taking advantage of the spontaneous remyelination occurring in this model upon suspending cuprizone administration we assessed the potential benefits of myelin re-gain by combining voltage sensitive dye imaging techniques, extracellular recordings and behavior.
Results: Decreased neuronal network activation was observed following demyelination in all cortical layers (-65.8 % vs. control) accompanied by increased latency to response (8.9 ms vs. 12.4 ± 0.06 ms). Heat maps showed a transitory hyperexcitation during the early remyelination phase (7 days) associated to altered spreading of the incoming cortical information into A1. Further analysis of the hierarchical activation of the different cortical layers revealed that a delayed activation of the cortical interneurons in layer 4 (0.005 ms longer than control) could mediate the hyperexcitation and the altered spreading of activity. Demyelination was also associated with a permanent loss of the tonotopic cortical organization in vivo, and the inability to induce tone-frequency-dependent conditioned behaviors, a status persistent after full remyelination (25 days).
Conclusions: Demyelination altered the functionality of auditory neuronal networks and the persistency of alterations would indicate that despite myelin re-growth was necessary but not sufficient to ameliorate an irreversibly compromised network. Moreover, the molecular mechanisms underlying the hyperexcitation observed during the early phase of remyelination should be further investigated given the effect of a prolonged higher excitability of neurons.
Disclosure: This study was supported by the DFG CRC TRG128 -B06
Manuela Cerina: nothing to disclose
Venu Narayanan: nothing to disclose
Patrick Meuth: nothing to disclose
Kerstin Göbel: nothing to disclose
Alexander M. Herrmann: nothing to disclose
Stephanie Graebenitz: nothing to disclose
Thiemo Daldrup: nothing to disclose
Thomas Seidenbecher: nothing to disclose
Heinz Wiendl: nothing to disclose
Erwin J. Speckmann: nothing to disclose
Hans-Christian Pape: nothing to disclose
Sven G. Meuth: nothing to disclose
Thomas Budde: nothing to disclose