The brainstem noradrenergic locus coeruleus (LC) is reciprocally connected with the prefrontal cortex (PFC). Strong coupling between LC spiking and depolarizing phase of slow (1 - 2 Hz) waves in the PFC field potentials during sleep and anesthesia suggests that the 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 direct electrical (or

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... ptogenetic) stimulation paradigms. Here, we describe the physiological characteristics of naturally occurring top-down prefrontal-coerulear interactions. Specifically, we recorded LC multi-unit 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 population spike rate and the power of PFC LFP oscillations within the high Gamma (hGamma) range (60 - 200 Hz). Specifically, transient increases in PFC hGamma power preceded peaks in the ~5 Hz LC-MUA oscillation. Analysis of cross-regional transfer entropy demonstrated that the PFC hGamma transients were predictive of a transient increase in LC-MUA. A ~29 msec delay between these signals was consistent with the conduction velocity from the PFC to the LC. Finally, we showed that PFC hGamma transients are associated with synchronized spiking of a subset (27%) of PFC single units. Our data suggest that, PFC hGamma 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 hGamma transients may provide a previously unknown mode of top-down control over the LC.