Datensatz

Zusammenfassung

Various states of wakefulness, perceptual ability, and locomotor activity are associated with
different cortical states defined by local field potential (LFP) oscillatory content. The brainstem
nucleus, Locus Coeruleus (LC), contributes to cortical state via noradrenergic projections
to nearly the entire central nervous system. Electrical or optogenetic LC stimulation evokes
increased high-frequency (HF, >20 Hz) cortical LFP oscillations and decreased low-frequency
(LF, <12 Hz) oscillations in anesthetized and non-anesthetized experiments and evokes awakening
in sleeping mice. The LC stimulation-evoked cortical state is due to highly synchronous
whole-LC neuronal activation because about 1600 neurons are densely packed into only about
200 × 500 × 1000μm (in rats) and stimulation even at the lower end of the current range used
in these studies (30–50μA) evokes spikes 400um from the stimulation site. These studies established
the conceptual model that LC generates a single aroused cortical state.
Recently, however, recordings of spontaneous LC single unit spiking demonstrated that pairs of
LC neurons have sparse, yet structured time-averaged cross-correlations that are uncharacteristic
of the en masse population event elicited by LC stimulation. It remains unknown whether
spontaneous LC population activity consists of multi-cell ensembles or how LC ensemble activity
evolves over time. Here, we used non-negative matrix factorization (NMF) to analyze large
populations of simultaneously recorded LC single units in the urethane anesthetized rat. NMF,
unlike traditional time-averaged pairwise correlations, detects the precise neuronal composition
of LC ensembles and the evolution of their activity over time. We found that LC population
dynamics consists of ensembles of co-active neurons with largely non-overlapping activation
dynamics.
We then characterized the relationship between LC ensemble activation dynamics and cortical
state. We calculated cortical LFP (area 24a) band-limited power and spectrograms aligned to
spontaneous activations of LC ensembles. Spontaneous activation of distinct LC ensembles
was associated with a diverse pool of cortical states. Depending on which LC ensemble fired,
we observed a diverse state space of increased HF and LF, decreased HF and LF, and opposing
HF and LF power. Thus, LC is not simply a switch controlling a single arousal-associated cortical state.