Inhibitory synaptic loss drives network changes in multiple sclerosis: An ex vivo to in silico translational study.

ABSTRACT:

Background

Synaptic and neuronal loss contribute to network dysfunction and disability in multiple sclerosis (MS). However, it is unknown whether excitatory or inhibitory synapses and neurons are more vulnerable and how their losses impact network functioning.

Objective

To quantify excitatory and inhibitory synapses and neurons and to investigate how synaptic loss affects network functioning through computational modeling.

Methods

Using immunofluorescent staining and confocal microscopy, densities of glutamatergic and GABAergic synapses and neurons were compared between post-mortem MS and non-neurological control cases. Then, a corticothalamic biophysical model was employed to study how MS-induced excitatory and inhibitory synaptic loss affect network functioning.

SUBMITTER: Huiskamp M 

PROVIDER: S-EPMC9574900 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature