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

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 in vivo 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.