In order to sustain consciousness, the cerebral cortex needs to be kept stimulated by thalamo-cortical inputs, and by inputs from other subcortical structures including the ascending reticular activating system (ARAS) in the brain stem.
For example, the ascending neural pathways that shift the slow wave activity of deep sleep to an activated state involve cholinergic neurons of the pedunculo-pontine tract nuclei and adrenergic neurons of the locus coeruleus, both in the brain stem. The locus coeruleus consists of about 50,000-60,000 neurons which utilise noradrenaline as a neurotransmitter. Their axons project widely to the entire cerebral cortex. Experimental activation of these pathways triggers fast (20-40 Hz gamma waves) neocortical rhythms by blocking slow after-hyperpolarisations in cortical neurons, thereby interrupting the slow waves of deep sleep1. This is a form of neuromodulation, functionally equivalent to having a dial that can turn up or down the gain of activity of the cortex2.
Conversely antagonists to the receptors for noradrenaline block the activation of the cortex, resulting in the appearance of slow wave activity like the slow waves observed in the cortex during coma, anaesthesia, or epileptic seizures3. Noradrenergic input from the locus coeruleus also abolishes rhythmic firing of the thalamus4.
Dopaminergic and serotonergic inputs from lower centres to the cortex also promote states of arousal5.
- M Steriade et al (1996): Synchronization of fast (30–40 Hz) spontaneous cortical rhythms during brain activation. Journal of Neuroscience 16, 392–417;
L Muller & A Destexhe (2012): Propagating waves in thalamus, cortex and the thalamocortical system: Experiments and models. Journal of Physiolology 106, 222–238;
RC Foehring et al (1989): Norepinephrine selectively reduces slow Ca2+ -and Na+– mediated K+currents in cat neocortical neurons. Journal of Neurophysiology 61, 245-256. ↩︎ - I Stitt et al (2018): Arousal dependent modulation of thalamo-cortical functional interaction Nature Communications 9, 2455;
J Martin et al (2022): Noradrenergic modulation of rhythmic neural activity shapes selective attention. Trends in Cognitive Sciences 26, 38-52;
RM Neves et al (2018): Locus coeruleus phasic discharge is essential for stimulus-induced gamma oscillations in the prefrontal cortex. Journal of Neurophysiology 119, 904-920:
G Wainstein et al (2022): The role of the locus coeruleus in shaping adaptive cortical melodies. Trends in Cognitive Science 26, 527-538. ↩︎ - M Steriade et al (1993): Cholinergic and noradrenergic modulation of slow (approximately 0.3 Hz) oscillation in neocortical cells. Journal of Neurophysiology 70, 1385-1400. ↩︎
- C Rodenkirch et al (2022) Locus coeruleus activation enhances thalamic feature selectivity via norepinephrine regulation of intrathalamic circuit dynamics. Nature Neuroscience 22, 120-133. ↩︎
- LE Suárez et al (2020): Linking structure and function in macroscale brain networks. Trends in Cognitive Sciences, 24, 302-315. ↩︎