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Abstract

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 LC-PFC interactions. 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-MUA and the power of PFC LFP high gamma (hGamma) activity. 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.