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Abstract:
The activity of all major ascending neuromodulatory arousal systems is greatly re-
duced during the periods of cortical synchronization that are reflected in EEG as
high-amplitude low-frequency waves. Despite the relative silence, neuromodulatory
neurons typically switch their firing pattern from a tonic mode during the alert,
desynchronized cortical state to a bursting mode during cortical synchronization
that is characteristic for slow wave sleep (SWS) or anesthesia. The bursting activity
is particularly efficient for a corresponding release of neuromodulators in the target
regions. The activity of brainstem cholinergic and dopaminergic neurons correlates
with cortical slow oscillations, while activity of the noradrenergic system in this context
remains unexplored. We recorded unit activity of the noradrenergic neurons of the
locus coeruleus (LC) with simultaneous monitoring of the cortical state by EEG in
behaving rats. Here we report that the activity of LC neurons is phase-locked to cortical
slow oscillations indicative of up-down states. In addition, we show that LC neurons
lock best to slow oscillations advanced by approximately 100 ms, suggesting a possible
noradrenergic contribution to generation of cortical up state. These results provide the
first strong evidence for a cortico-coerulear interaction during SWS and challenge a
conventional dogma about a quiescent state of the LC-noradrenergic system during
sleep. The phase-locking of noradrenergic neurons to cortical slow oscillations may
have a strong impact on the coordinated activity of neuronal assemblies during up
states, which might be relevant for off-line information processing, synaptic plasticity
and memory consolidation.