Interleukin-1β Alters Hebbian Synaptic Plasticity in Multiple Sclerosis

Area of Science:

• Neuroscience
• Neuroimmunology
• Neurophysiology

Background:

• Inflammation significantly impacts synaptic transmission and plasticity in multiple sclerosis (MS).
• The proinflammatory cytokine Interleukin-1 beta (IL-1β) is implicated in MS pathogenesis.
• Understanding how IL-1β affects specific forms of synaptic plasticity is crucial for MS research.

Purpose of the Study:

• To investigate the influence of IL-1β on Hebbian synaptic plasticity, specifically input specificity, in relapsing-remitting MS patients.
• To examine the relationship between cerebrospinal fluid (CSF) IL-1β levels and synaptic plasticity measures.
• To assess intracortical excitability and its association with IL-1β in MS.

Main Methods:

• Paired associative stimulation (PAS) applied to the abductor pollicis brevis (APB) muscle in 33 MS patients and 15 healthy controls.
• Assessment of motor-evoked potentials (MEPs) in APB and abductor digiti minimi (ADM) muscles post-PAS.
• Measurement of intracortical excitability using paired-pulse transcranial magnetic stimulation (TMS) and quantification of CSF IL-1β levels.

Main Results:

• MS patients showed impaired long-term potentiation (LTP)-like effects after PAS in the APB muscle.
• A paradoxical increase in MEPs was observed in the ADM muscle of MS patients.
• Higher IL-1β levels correlated negatively with LTP-like responses and were associated with increased synaptic hyperexcitability.

Conclusions:

• IL-1β significantly disrupts Hebbian synaptic plasticity in MS, potentially causing a loss of topographic specificity.
• Synaptic hyperexcitability, driven by IL-1β, may be a key mechanism underlying altered plasticity in MS.
• These findings highlight the role of neuroinflammation in synaptic dysfunction in multiple sclerosis.