Diurnal Modulation of Locus Coeruleus Noradrenergic Neurons in Anesthetized Adult Male Rats.

Unlabelled: The locus coeruleus (LC) is the primary source of noradrenaline (NA) in brain and its activity is essential for learning, memory, stress, arousal, and mood. LC-NA neuron activity varies over the sleep-wake cycle, with higher activity during wakefulness, correlating with increased CSF NA levels. Whether spontaneous and burst firing of LC-NA neurons during active and inactive periods is controlled by mechanisms independent of wakefulness and natural sleep, is currently unknown. Here, using multichannel electrophysiology under anesthesia, we assessed LC-NA neuron firing in adult male Fisher 344 rats at two different times of day- ZT4- the inactive period (light phase) and ZT16-the active period (dark phase)- independent of contributions from behavioral arousal and natural sleep. In the dark phase, LC-NA neurons exhibit increased average firing rate during baseline compared to the light phase. Using a relatively weak foot shock paradigm, we observed distinct populations of LC-NA neurons with some increasing, and others decreasing, their firing rate compared to baseline. Additionally, while spike frequency during spontaneous and evoked bursts is consistent across the dark-light phase, units recorded during the dark phase have more frequent bursts with a longer duration than those during the light phase. Our findings show that independent of wake state, LC-NA neurons exhibit intrinsic diurnal activity, and that the variability of response to foot shock stimulation demonstrates a physiological heterogeneity of LC-NA neurons that is just beginning to be appreciated.

New & Noteworthy: Multichannel electrophysiology assesses activity of large populations of NA neurons within an intact LC. Recording activity under anesthesia eliminates influence of behavior and sleep on LC-NA neuron physiology. Our data show that LC-NA neurons have heightened firing and burst activity during the dark phase, suggesting a hardwired diurnal rhythm. Additionally, LC-NA neurons have variable evoked firing highlighting heterogeneity, consistent with a contemporary view that LC physiology is more complex than previously appreciated.