Impairment of thalamo-cortical network activities in animal models of multiple sclerosis

Abstract

Introduction: Infiltration of immune cells, demyelination, axonal damage and neuronal degeneration are all indicative of the impaired interplay between the immuneandnervous systemduringmultiple sclerosis (MS). The neuroinflammatory events and resulting alterations in neuronal excitability can cause changes in synaptic network function. The aim of this study was to evaluate the hypothesis that distinct histopathological changes like inflammation or demyelination can lead to alterations in neuronal network activities in thalamo-cortical network system. Methods: Control and cuprizone treated mice (general demyelination in the CNS) unilaterally equipped with micro-wire arrays (MWA, 1 array, 8 electrodes and one reference/array per brain region) in the 4th layer of the auditory cortex (AC-IV) and ventral part of the Medial Geniculate Nucleus (MGNv) of the thalamus. Unit activities were recorded before, during and after the presentation of auditory stimuli (2.5 and 10 kHz, 6 times each). The spikes of individual neurons were sorted by a time-amplitude window discrimination and principal component analysis and verified through quantification of cluster analysis. Baseline as well as stimulus-related neuronal firing rates were analyzed and compared between the demyelinated, remyelinating and remyelinated mice. Results: Compared to control mice, demyelinated mice show decreased neuronal activities, but with the time during remyelination, the activity comes back. In addition to that, the control mice show neuronal response to high frequency (10 kHz) auditory stimuli, but the cuprizone treated mice are not able to discriminate between high (10 kHz) and low frequency (2.5 kHz) auditory stimuli. Conclusion: Neurons in auditory cortex and auditory thalamus possess response specificity and discrimination properties. But after cuprizone treatment, sensory responsiveness is abolished and slowly recovers with remyelination, although discrimination properties and specificity remain impaired. Acknowledgements: This work is supported by the CRC TR 128, B6, Meuth, Pape and Budde.