Elsevier

Neuroscience

Volume 169, Issue 3, 1 September 2010, Pages 1115-1126
Neuroscience

Cognitive, Behavioral, and Systems Neuroscience
Research Paper
Locus coeruleus neuronal activity during the sleep-waking cycle in mice

https://doi.org/10.1016/j.neuroscience.2010.06.009Get rights and content

Abstract

Using extracellular single-unit recordings in nonanesthetized, head-restrained mice, we examined spontaneous and evoked discharges of noradrenaline-containing locus coeruleus (NA-LC) neurons across the sleep-waking cycle. The neurons were all characterized by triphasic broad action potentials. They discharged as either slow (<6 Hz) tonic, single spikes or phasic clusters of spikes specific to wakefulness (W), the discharge rate being highest during active waking and significantly lower during quiet waking. They remained totally silent during both slow-wave sleep (SWS) and paradoxical (or rapid eye movement (REM)) sleep. The phasic unit activity was related to abrupt activation of electromyographic activity occurring either spontaneously or elicited by alerting sensory stimuli. At the transition from waking to sleep, they ceased firing before the onset of cortical synchronization (deactivation), the first sign of electroencephalographic sleep, a significant decrease in firing rate preceding the onset of unit activity of sleep-specific neurons in the basal forebrain (BFB)/preoptic (POA) hypothalamus, as described previously [Takahashi K, Lin JS, Sakai K (2009) Neuroscience 161:269–292]. At the transition from SWS to waking, they fired before the onset of both cortical activation and a significant decrease in activity of sleep-specific neurons. These findings support the previous view that the NA-LC system is involved in both tonic and phasic processes of arousal, and further support our previous proposals that initiation of sleep is caused by decreased activity of waking-promoting neurons (disfacilitation) and that NA-LC neurons play an important role in the sleep/waking switch, that is from waking to sleep and from sleep to waking [Takahashi K, Lin JS, Sakai K (2009) Neuroscience 161:269–292].

Section snippets

Animals and surgery

All procedures were approved by the University of Lyon 1 Animal Care Committee, the standards of which meet those of the EEC Guidelines (86/609/EEC) and the Policy on Ethics approved by the Society for Neuroscience (1993). All efforts were made to minimize the number of animals used and their suffering.

Fifteen male adult C57BL/6 mice (Harlan, France; 25–34 g at the time of surgery) were used. The mice were anesthetized using a mixture of 0.8 mg/ml of ketamine (Imalgene 1000, Merial, Lyon,

Results

Extracellular single unit recordings were made from a total of 71 NA-LC neurons during the complete sleep-waking cycle, including at least one PS. In light of previous studies in rats demonstrating the presence of distinct topographic distribution within the NA-LC (Loughlin et al., 1986, España and Berridge, 2006), we divided the LC into rostral, middle, and caudal regions, as shown in Fig. 1, in which the histological localization of the recording sites is depicted. As shown in this figure,

Discussion

For the first time in non-anesthetized, head-restrained mice, we have determined the properties and activity profiles of the single-unit discharge of NA-LC neurons during the complete sleep-waking cycle and their state transitions. We found that the neurons exhibited a remarkably homogeneous spike shape and pattern of unit activity: (1) they displayed triphasic, broad action potentials and were active only during W, discharging as either single spikes or clusters of 2–6 spikes; (2) they

Conclusion

The present study suggests that the sleep process does not start with the activation of forebrain sleep-promoting neurons, but with a cascade of disfacilitation of forebrain and brainstem waking-promoting neurons, NA-LC neurons playing a central role in this process.

Acknowledgments

This study was supported by INSERM U628 and Claude Bernard University in France and the Ministry of Education, Culture, Sports, Science and Technology, Grant-in-Aid for Scientific Research(C), 20500288, 2009 in Japan.

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