Membrane potential states gate synaptic consolidation in human neocortex

Synaptic mechanisms that contribute to memory consolidation in the human brain remain largely unexplored. The formation of lasting memories critically relies on sleep ^1-3 . During slow wave sleep, neocortical neurons exhibit characteristic membrane potential oscillations known as UP and DOWN states ^4-7 . In this study, we show that sleep-like UP and DOWN states modulate axonal action potentials and temporarily enhance synaptic transmission between human layer 2 & 3 pyramidal neurons. In convergent microcircuit motifs, synaptic enhancement by synchronous UP and DOWN states leads to efficient recruitment of postsynaptic action potentials, which in turn results in long-term stabilization of synaptic strength. In contrast, synapses undergo lasting depression if presynaptic neurons fail to recruit postsynaptic action potentials. Taken together, our study offers a mechanistic framework in humans that can explain how precise coupling of neural activity to slow waves gates synaptic plasticity, which is the substrate of memory consolidation ^8-12 . This framework could inspire improved brain stimulation strategies targeting memory performance ^13-18 .