Sleep waves in a large-scale corticothalamic model constrained by activities intrinsic to neocortical networks and single thalamic neurons

ABSTRACT Aim Many biophysical and non-biophysical models have been able to reproduce the corticothalamic activities underlying different EEG sleep rhythms but none of them included the known ability of neocortical networks and single thalamic neurons to generate some of these waves intrinsically. Methods We built a large-scale corticothalamic model with a high fidelity in anatomical connectivity consisting of a single cortical column and first- and higher-order thalamic nuclei. The model is constrained by different neocortical excitatory and inhibitory neuronal populations eliciting slow (<1 Hz) oscillations and by thalamic neurons generating sleep waves when isolated from the neocortex. Results Our model faithfully reproduces all EEG sleep waves and the transition from a desynchronized EEG to spindles, slow (<1 Hz) oscillations and delta waves by progressively increasing neuronal membrane hyperpolarization as it occurs in the intact brain. Moreover, our model shows that slow (<1 Hz) waves most often start in a small assembly of thalamocortical neurons though occasionally they originate in cortical layer 5. Moreover, thalamocortical neuron input increases the frequency of slow (<1 Hz) waves compared to those generated by isolated cortical networks. Conclusion Our simulations challenge current mechanistic understanding of the temporal dynamics of sleep wave generation and suggest testable predictions.