Modeling the evolving oscillatory dynamics of the rat locus coeruleus through early infancy

The mammalian locus coeruleus (LC) is a brainstem structure that displays extensive interconnections with numerous brain regions, and in particular plays a prominent role in the regulation of sleep and arousal. Postnatal LC development is known to drastically alter sleep-wake switching behavior through early infancy, and, in rats, exerts its most significant influence from about postnatal day 8 to postnatal day 21 (P8-P21). Physiologically, several dramatic changes are seen in LC functionality through this time period. Prior to P8, LC neurons are extensively coupled via electrical gap junctions and chemical synapses, and the entire LC network exhibits synchronized ~0.3 Hz subthreshold oscillations and spiking. From P8 to P21, the network oscillation frequency rises up to ~3 Hz (at P21) while the amplitude of the network oscillation decreases. Beyond P21, synchronized network oscillations vanish and gap junction coupling is sparse or nonexistent. In this work, we develop a large-scale, biophysically realistic model of the rat LC and we use this model to examine the changing physiology of the LC through the pivotal P8-P21 developmental period. We find that progressive gap junction pruning is sufficient to account for all of the physiological changes observed from P8 to P21.