Stimulation of Locus Coeruleus Noradrenergic System Modulates Sensory Processing and Brain State in two Different Time Scales

Locus Coeruleus (LC) noradrenergic system has widespread projections throughout the brain and affects sensory processing. LC modulation of sensory-evoked cortical activity and brain state is documented by electrical micro-stimulation, optogenetic experiments, and the local application of norepinephrine (NE). The temporal profile of the LC modulation of sensory response and brain state is not well characterized. Our goal in this study is to characterize this modulation. Here, we recorded neuronal activity from the barrel cortex (BC) of urethane-anesthetized rats while combining LC micro-stimulation with brief mechanical deflections of the whiskers at 10 different time lags (50-500 ms). We recorded spikes and local field potentials to quantify the neuronal activity and the brain state. LC micro-stimulation exhibited a biphasic effect on spontaneous activity of the BC: a period of suppression followed by a period of excitation. We observed a similar effect on the sensory-evoked response: at 50-ms lag, the evoked response decreased while at 150-ms lag, the early evoked response was facilitated. At 150 to 350-ms time lags, LC micro-stimulation caused a combined facilitation followed by suppression of the evoked response. In contrast to the fast transient effect of LC stimulation on BC spiking activity, brain state modulation started later and lasted longer. LC stimulation suppressed low-frequency activities that are associated with low arousal states. In summary, we found that LC modulation affects cortical processing of sensory inputs and the brain state at different time scales which are likely to involve distinct circuit mechanisms.