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Abstract

The brain stem noradrenergic nucleus Locus Coeruleus (LC) is the primary source of norepinephrine (NE) in the forebrain. The LC-NE system plays a critical role in regulating arousal state, it mediates many visceral responses and also involved in a variety of cognitive functions including learning and memory. Enhanced tonic firing of LC neurons during sleep is associated with a decrease in the occurrence of hippocampal ripples and sleep spindles; both oscillatory events have been suggested to mediate the hippocampal-cortical communication underlying systems-level consolidation. Experimentally induced ripple-triggered phasic LC activation during post-learning sleep causes memory deficit, possibly due to interference with cellular- and systems-level memory consolidation mechanisms. At present, the involvement of LC-NE system in the hippocampal-cortical information transfer remains largely unexplored. In the present study, we examined temporal coupling between the LC spiking activity, hippocampal ripples, and sleep spindles. The multiunit (MUA) recordings were obtained from the LC simultaneously with the local field potentials (LFPs) from the CA1 subfield of dorsal hippocampus and the prefrontal cortex in rats during spontaneous behavior. In general, the LC-MUA was suppressed around ripples and elevated around sleep spindles. Systematic fluctuations of LC-MUA around ripples occurred at faster (~500 ms) and slower (~10 sec) temporal scales. Specifically, a gradual reduction of LC tonic firing occurred ~10 sec preceding ripple oscillation and an additional sharp transient decrease of LC-MUA was observed ~ 1 sec prior the ripple onset. Notably, the most pronounced LC modulation at slower time scale occurred before ripples co-occurring with sleep spindles. The degree of LC activity modulation at faster time scale was comparable among awake or sleep ripples. Fast LC-MUA modulation was essentially absent around ripples coupled with sleep spindles. Our results suggest that the LC activity suppression may facilitate transition to a specific brain state that is favorable for ‘off-line’ inter-regional information transfer.