Neuroinflammation in Synaptic Plasticity: Cellular Mechanisms and Cognitive Implications

Synaptic plasticity—the brain’s ability to strengthen, weaken, or reorganize synaptic connections—is essential for learning, memory, and cognitive adaptation. Traditionally studied through mechanisms like long-term potentiation (LTP) and long-term depression (LTD), plasticity has often been viewed in isolation from the brain’s immune system. However, growing evidence reveals that neuroinflammation—a response mediated by microglia, astrocytes, cytokines, and complement proteins—profoundly influences synaptic dynamics across the lifespan.This review examines how neuroinflammation modulates synaptic plasticity under both physiological and pathological conditions. We first describe the cellular and molecular mediators of neuroinflammation and their interactions with core mechanisms of synaptic modulation. Next, we explore how chronic inflammatory signaling impairs synaptic strength, promotes excessive pruning, and alters dendritic spine architecture. These changes are linked to cognitive dysfunction in conditions such as Alzheimer’s disease, multiple sclerosis, major depression, and schizophrenia. Finally, we evaluate emerging therapeutic strategies—including anti-inflammatory drugs, microglial modulators, lifestyle interventions, and precision medicine approaches—aimed at preserving synaptic function and cognitive resilience.By synthesizing current findings, this review highlights neuroinflammation as a central regulator of plasticity and a promising target for interventions that restore neural health across a range of neurodegenerative and neuropsychiatric disorders.