Hydrogen Sulfide (H₂S- or H₂S_n-Polysulfides) in Synaptic Plasticity: Modulation of NMDA Receptors and...

Hydrogen sulfide (H₂S) has emerged as a pivotal gaseous transmitter in the central nervous system, influencing synaptic plasticity, learning, and memory by modulating various molecular pathways. This review examines recent evidence regarding how H₂S regulates NMDA receptor function and neurotransmitter release in neuronal circuits. By synthesizing findings from animal and cellular models, we investigate the impacts of enzymatic H₂S production and exogenous H₂S on excitatory synaptic currents, long-term potentiation, and intracellular calcium signaling. Data suggest that H₂S interacts directly with NMDA receptor subunits, altering receptor function and modulating neuronal excitability. Simultaneously, H₂S promotes the release of neurotransmitters such as glutamate and GABA, shaping synaptic dynamics and plasticity. Furthermore, reports indicate that disruptions in H₂S metabolism contribute to cognitive impairments and neurodegenerative disorders, underscoring the potential therapeutic value of targeting H₂S-mediated pathways. Although the precise mechanisms of H₂S-induced changes in synaptic strength remain elusive, a growing body of evidence positions H₂S as a significant regulator of memory formation processes. This review calls for more rigorous exploration into the molecular underpinnings of H₂S in synaptic plasticity, paving the way for novel pharmacological interventions in cognitive dysfunction.