How does the brain move between deep sleep, drowsiness and alert wakefulness? Researchers at Newcastle University's Neural Circuits Laboratory and Biosciences Institute, working with the Blue Brain Project at EPFL and partners in Spain, mapped the density and spatial distribution of neuromodulatory fibres across every layer of the rat somatosensory cortex, then built those measurements into a detailed computational model of a cortical microcircuit.
Simulating how acetylcholine, dopamine and serotonin alter the electrical behaviour of tens of thousands of neurons produced a remarkably specific division of labour. Acetylcholine, whose fibre varicosity density was 2.3 times greater than the serotonergic system's, suppressed the slow delta waves characteristic of deep sleep. Dopamine and serotonin desynchronised cortical activity and damped slow oscillations, serotonin uniquely promoted faster theta rhythms, and dopamine showed the broadest reach, acting on excitatory and inhibitory neurons across all layers.
Published in PLOS Computational Biology, the work offers a mechanistic bridge between neurochemistry and the large-scale brain states that anaesthetists, sleep scientists and psychiatrists care about in daily practice. Because the model is quantitative and openly described, it provides a testbed for predicting how drugs that target these neuromodulator systems might shift the cortex between states of consciousness.