Synchronous spiking associated with prefrontal high γ oscillations evokes a 5-Hz rhythmic modulation of spiking in...

The brainstem noradrenergic locus coeruleus (LC) is reciprocally connected with the prefrontal cortex (PFC). Coupling between LC spiking and the depolarizing phase of slow (1-2 Hz) waves in PFC field potentials during sleep and anesthesia suggests that LC drives cortical state transition. Reciprocal LC-PFC connectivity should also allow interactions in the opposing (top-down) direction, but prior work has only studied prefrontal control over LC activity using electrical or optogenetic stimulation. Here, we describe the physiological characteristics of spontaneously occurring top-down LC-PFC interactions. We recorded LC multiunit activity (MUA) simultaneously with PFC single-unit and local field potential (LFP) activity in urethane-anesthetized rats. We observed cross-regional coupling between the phase of 5-Hz oscillations in LC-MUA and the power of PFC LFP 60-200 Hz high γ (hγ). Transient increases in PFC hγ power preceded peaks in the 5-Hz LC-MUA oscillation. Analysis of cross-regional transfer entropy demonstrated that the PFC hγ transients were predictive of a transient increase in LC-MUA. An ∼29 ms delay between these signals was consistent with the conduction velocity from the PFC to the LC. Finally, we showed that PFC hγ transients are associated with synchronized spiking of a subset (27%) of PFC single units. Our data suggest that PFC hγ transients may indicate the timing of the top-down excitatory input to LC, at least under conditions when LC neuronal population activity fluctuates rhythmically at 5 Hz. Synchronized PFC neuronal spiking that occurs during hγ transients may provide a previously unknown mode of top-down control over the LC.NEW & NOTEWORTHY The prefrontal cortex (PFC) is thought to control activity in the noradrenergic locus coeruleus (LC). Prior anatomical and prefrontal stimulation studies demonstrated the potential for PFC-LC interactions; however, it is unknown what types of PFC activity affect the LC. Here, we show that transient increases in PFC high γ power and associated changes in PFC unit-pair synchrony are a potential sign of top-down control over the LC.