Impairment of frequency-specific responses associated with altered electrical activity patterns in auditory thalamus following focal and general demyelination

Exp Neurol. 2018 Nov;309:54-66. doi: 10.1016/j.expneurol.2018.07.010. Epub 2018 Jul 23.

Abstract

Multiple sclerosis is characterized by intermingled episodes of de- and remyelination and the occurrence of white- and grey-matter damage. To mimic the randomly distributed pathophysiological brain lesions observed in MS, we assessed the impact of focal white and grey matter demyelination on thalamic function by directing targeted lysolecithin-induced lesions to the capsula interna (CI), the auditory cortex (A1), or the ventral medial geniculate nucleus (vMGN) in mice. Pathophysiological consequences were compared with those of cuprizone treatment at different stages of demyelination and remyelination. Combining single unit recordings and auditory stimulation in freely behaving mice revealed changes in auditory response profile and electrical activity pattern in the thalamus, depending on the region of the initial insult and the state of remyelination. Cuprizone-induced general demyelination significantly diminished vMGN neuronal activity and frequency-specific responses. Targeted lysolecithin-induced lesions directed either to A1 or to vMGN revealed a permanent impairment of frequency-specific responses, an increase in latency of auditory responses and a reduction in occurrence of burst firing in vMGN neurons. These findings indicate that demyelination of grey matter areas in the thalamocortical system permanently affects vMGN frequency specificity and the prevalence of bursting in the auditory thalamus.

Keywords: Burst activity; Demyelination; Multiple sclerosis; Remyelination; Single unit activity; Thalamocortical system; Thalamus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation / methods
  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Auditory Cortex / drug effects
  • Auditory Cortex / physiopathology
  • Cuprizone / toxicity
  • Demyelinating Diseases / chemically induced
  • Demyelinating Diseases / drug therapy
  • Demyelinating Diseases / pathology*
  • Demyelinating Diseases / physiopathology
  • Disease Models, Animal
  • Female
  • Functional Laterality
  • Geniculate Bodies / pathology
  • Gliosis / chemically induced
  • Gliosis / pathology
  • Gray Matter / pathology
  • Lysophosphatidylcholines / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Monoamine Oxidase Inhibitors / toxicity
  • Myelin Proteolipid Protein / metabolism
  • Neurons / drug effects
  • Neurons / physiology
  • Psychoacoustics
  • Thalamus / drug effects
  • Thalamus / physiopathology*

Substances

  • Lysophosphatidylcholines
  • Monoamine Oxidase Inhibitors
  • Myelin Proteolipid Protein
  • Cuprizone