Stereotyped large amplitude cortical LFP events can be clustered and reveal precisely ordered phase-locking in neuronal populations

During quiet wakefulness, slow-wave sleep and anesthesia, mammalian cortex exhibits a synchronised state during which transient changes in the local field potential (LFP) accompany periods of increased single neuron firing, known as UP-states. While UP-state genesis is still debated (Crunelli and Hughes, 2010) such transitions may constitute the default activity pattern of the entire cortex (Neske, 2016). Recent findings of preserved firing order between UP-state transitions and stimulus processing in high-firing rate (>2Hz) rat auditory and barrel cortex neurons (Luczak et al., 2015) support this hypothesis. Yet it is unknown whether UP-states are homogeneous and whether neurons with firing rates <2Hz in visual cortex or other species exhibit spiking order. Using extracellular recordings during anesthetized states in cat visual cortex and mouse visual, auditory and barrel cortex, we show that UP-states can be tracked and clustered based on the shape of the LFP waveform. We show that LFP event clusters (LECs) have current-source-density profiles that are common across different recordings or animals and using simultaneous electrophysiology and widefield voltage and calcium imaging in mouse we confirm that LEC transitions are cortex-wide phenomena. Individual LEC events can be resolved in time to within 1 - 4 ms and they elicit synchronous firing of over 75% of recorded neurons with most neurons synchronizing their firing to within {+/-}5 - 15 ms relative LECs. Firing order of different neurons during LEC events was preserved over periods of ~30 minutes enabling future studies of UP-state transitions and firing order with near millisecond precision.\n\nSignificant StatementDuring sleep and anesthetic states mammalian cortex undergoes substantial changes from awake active states. Recent studies show that single neurons in some cortical areas in rats undergo increased spiking during sleep and anesthetic states (called UP-state transitions) with some neurons firing in an order similar to awake states. This suggests that sensory processing may be similar across all states and that firing order is important for stimulus processing. Yet UP-state transitions remain poorly understood and it is unclear whether firing order is present in other cortical areas or species. Here we describe multiple classes of UP-state transitions and show most neurons in visual cortex in cats and visual, barrel and auditory cortex in mice exhibit firing order during such transitions.