Deterministic and Stochastic Components of Cortical Down States: Dynamics and Modulation

Slow oscillations are an emergent activity of the cerebral cortex network consisting of alternating periods of activity (Up states) and silence (Down states). Up states are periods of persistent cortical activity that share properties with that of under-lying wakefulness. However, the occurrence of Down states is almost invariably associated with unconsciousness, both in ani-mal models and clinical studies. Down states have been attributed relevant functions, such as being a resetting mechanism or breaking causal interactions between cortical areas. But what do Down states consist of? Here, we explored in detail the network dynamics (e.g., synchronization and phase) during these silent periods in vivo (male mice), in vitro (ferrets, ei-ther sex), and in silico, investigating various experimental conditions that modulate them: anesthesia levels, excitability (electric fields), and excitation/inhibition balance. We identified metastability as two complementary phases composing such quiescence states: a highly synchronized "deterministic" period followed by a low-synchronization "stochastic" pe-riod. The balance between these two phases determines the dynamical properties of the resulting rhythm, as well as the responsiveness to incoming inputs or refractoriness. We propose detailed Up and Down state cycle dynamics that bridge cortical properties emerging at the mesoscale with their underlying mechanisms at the microscale, providing a key to understanding unconscious states.