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

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.