Locus Coeruleus phasic discharge is essential for stimulus-induced gamma oscillations in the prefrontal cortex

The Locus Coeruleus (LC) noradrenergic (NE) neuromodulatory system is critically involved in regulation of neural excitability via its diffuse ascending projections. Tonic NE release in the forebrain is essential for maintenance of vigilant states and increases the signal-to-noise ratio of cortical sensory responses. The impact of phasic NE release on cortical activity and sensory processing is less explored. We have previously reported that LC microstimulation caused a transient desynchronization of the population activity in the medial prefrontal cortex (mPFC), similar to noxious somatosensory stimuli. The LC receives nociceptive information from the medulla and therefore may mediate sensory signaling to its forebrain targets. Here, we performed extracellular recordings in LC and mPFC while presenting noxious stimuli in urethane-anesthetized rats. A brief train of foot shocks produced a robust phasic response in the LC and a transient change in the mPFC power spectrum with the strongest modulation in gamma (30-90 Hz) range. The LC phasic response preceded prefrontal gamma power increase and cortical modulation was proportional to the LC excitation. We also quantitatively characterized distinct cortical states and showed that sensory responses in both LC and mPFC depend on the ongoing cortical state. Finally, cessation of the LC firing by bilateral local iontophoretic injection of clonidine, α2-adrenoreceotor agonist, completely eliminated sensory responses in the mPFC without shifting cortex to less excitable state. Together, our results suggest that the LC phasic response induces gamma power increase in the prefrontal cortex and is essential for mediating sensory information along ascending noxious pathway.

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