Modulation of the cortical population dynamics by phasic activation of the locus coeruleus

Synchronized population activity in cortex is a hallmark of slow-wave sleep, quiet wakefulness, or anesthesia. Rhythmic uctuations of neuronal membrane excitability are rejected in extracellular field potentials as delta (1-4 Hz) or large-amplitude slow ( ~ 1Hz) oscillations (SO); the latter are indicative for Up-to-Down-states transitions. The Up-states comprise periods of neuronal membrane depolarization accompanied by sustained spiking activity; the Down-states are associated with membrane hyperpolarization and neuronal silence. The level of cortical synchronization depends on the input from a number of subcortical neuromodulatory centers, including the brainstem nucleus Locus Coeruleus (LC). The LC regulates cortical excitability via its direct or indirect ascending projections and norepinephrine (NE) release in the target regions. We have previously demonstrated that phasic LC activation causes transient cortical desynchronization. Here, we sought to characterize the effect of transient NE release on the cortical population dynamics at a fine temporal scale. To this end, we quantified the effects of the direct electrical stimulation of LC (LC-DES) on the Up/Down-state transition in the medial prefrontal cortex (mPFC) in urethane-anesthetized rats. Biphasic electric pulses (0.4 ms, 0.02-0.05 mA) were applied to the LC unilaterally at 50 Hz for 200 ms while mPFC activity was monitored ipsilateral to the simulation site. The effect of LC-DES on cortical population activity depended on the phase SO. The LC-DES presented within an Up-state prolonged the ongoing Up-state for 94.3 - 21.3 ms and caused ~20% increase of the firing rate in the mPFC. In addition, Down-states coincided with LC-DES were followed by a rapid transition to Upstate in ~20% of trials. Our results suggest that the effect of NE release on cortical population dynamics strongly depends on the cortical state preceding LC activation