Modeling Sleep and Wakefulness in the Thalamocortical System

Abstract

Hill, Sean and Giulio Tononi. Modeling sleep and wakefulness in the thalamocortical system. J Neurophysiol 93: 2005. First published November 10, 2004; doi:10.1152/jn.00915.2004. When the brain goes from wakefulness to sleep, cortical neurons begin to undergo slow oscillations in their membrane potential that are synchronized by thalamocortical circuits and reflected in EEG slow waves. To provide a self-consistent account of the transition from wakefulness to sleep and of the generation of sleep slow waves, we have constructed a large-scale computer model that encompasses portions of two visual areas and associated thalamic and reticular thalamic nuclei. Thousands of model neurons, incorporating several intrinsic currents, are interconnected with millions of thalamocortical, corticothalamic, and both intra-and interareal corticocortical connections. In the waking mode, the model exhibits irregular spontaneous firing and selective responses to visual stimuli. In the sleep mode, neuromodulatory changes lead to slow oscillations that closely resemble those observed in vivo and in vitro. A systematic exploration of the effects of intrinsic currents and network parameters on the initiation, maintenance, and termination of slow oscillations shows the following. 1) An increase in potassium leak conductances is sufficient to trigger the transition from wakefulness to sleep.2) The activation of persistent sodium currents is sufficient to initiate the up-state of the slow oscillation. 3) A combination of intrinsic and synaptic currents is sufficient to maintain the up-state. 4) Depolarization-activated potassium currents and synaptic depression terminate the up-state. 5) Corticocortical connections synchronize the slow oscillation. The model is the first to integrate intrinsic neuronal properties with detailed thalamocortical anatomy and reproduce neural activity patterns in both wakefulness and sleep, thereby providing a powerful tool to investigate the role of sleep in information transmission and plasticity.

Source modeling sleep slow waves

“…The propagation speed in source space ranged from 0.4 to 6.3 m/s. The average speed was Ϸ2.2 m/s, was remarkably consistent across subjects (ranging from 2.0 to 2.3 m/s), and was roughly in agreement with previous estimations from EEG and computer simulations (9,23). Visual inspection of the streamlines for the spontaneous slow waves for each subject suggested the existence of a mesial slow wave highway oriented along the anterior-posterior axis ( Fig.…”

“…Unit recording studies also support this interpretation (34). While cortical currents are typically thought to arise from the summation of inhibitory and excitatory postsynaptic potentials from the local neural population (13), synaptic input is greatly reduced during the downstate (23,(35)(36)(37). This suggests that postsynaptic potentials are not entirely responsible for the large currents recorded during a slow wave.…”

A single-cell level and connectome-derived computational model of the Drosophila brain

“…However, because the available combination of the neuron and synapse models do not exactly match those used in the Flysim simulator, we tested NEST with two sets of combinations, with one requiring more and the other requiring less computational power than our simulator. We first tested the HT model (Hill and Tononi 2005) in NEST because this model offers a synaptic dynamic that is comparable to that used in Flysim. However, the HT model is endowed with soma dynamics that are more complex than ours.…”

An analysis of the transitions between down and up states of the cortical slow oscillation under urethane anaesthesia

“…Hill and Tononi [6] have carried out simulations with a more comprehensive thalamocortical network that show the importance of cortical-cortical interactions in establishing and maintaining the oscillation. Experimental work on the cortical nature of the slow oscillation includes that of Steriade et al [7], who demonstrated that the slow oscillation is maintained in cat cortex following lesioning of the thalamus.…”

“…The depolarized "up" and hyperpolarized "down" states are viewed as stable solutions for the mean membrane potential, with the down-to-up transitions being driven possibly by spontaneous neurotransmitter release [12] or random summation of EPSPs [13], and the up-to-down transition driven possibly by voltage-gated ionic (e.g., K + ) currents [5,6,14], or changes in synaptic weight [6,15]. Molaee-Ardekani et al, using a broadly similar model, have taken a different view of the phenomenon, interpreting the small slow waves seen in light anaesthesia as small, unstable excursions away from the equilibrium state, and the large slow waves of deep anaesthesia as limit cycles of the bulk behavior of the cortex [16].…”