Membrane potential up/down-states enhance synaptic transmission in the human neocortex – A framework for memory consolidation during slow wave sleep

Synaptic mechanisms of memory consolidation in the human brain remain largely unexplored. During slow wave sleep, which is critical for memory formation, neocortical neurons exhibit characteristic membrane potential oscillations known as UP and DOWN states. We demonstrate that sleep-like UP and DOWN states modulate axonal action potentials and enhance synaptic transmission between human layer 2 & 3 pyramidal neurons. In the cortical microcircuit, synaptic enhancement by synchronous UP and DOWN states gives rise to efficient recruitment of action potentials in postsynaptic neurons, which in turn results in long-term stabilization of synaptic strength. Conversely, synapses undergo lasting depression if presynaptic neurons fail to trigger postsynaptic action potentials. Taken together, our study offers a mechanistic framework in humans that can explain how coupling of neural activity to slow waves gates synaptic plasticity. Graphical abstract: