Bazhenov, Maxim
Coauthors(s): Igor Timofeev (Sch. of Medicine, Laval University) Mircea Steriade (Sch. of Medicine, Laval University) Terrence Sejnowski (Salk Inst., UCSD)
Salk Institute, HHMI
CNL
10010 N. Torrey Pines Rd. La Jolla, CA 92037
www.cnl.salk.edu/~bazhenov

Slow wave sleep oscillations and transition to an awake state in a thalamocortical network model

Slow wave sleep (SWS) oscillations ( < 1Hz ) and their transformation to the active awake state were investigated with computational models of the thalamocortical system including thalamocortical (TC) and thalamic reticular (RE) cells, cortical pyramidal (PY) cells and inhibitory interneurons (IN). The summation of the miniature EPSPs during depth-positive (silent) phase of an oscillation could activate the persistent sodium current and depolarize the membrane of PY cells sufficiently for spike generation. Once the oscillations were initiated, they spread through the network and were maintained by the lateral PY-PY excitation and persistent sodium currents. Progressive depression of the excitatory interconnections and activation of Ca2+ dependent K+ current led to termination of the 20-25 Hz activity after 500-1000 ms. The number of neurons required for maintaining regular SWS oscillations under in vivo conditions was comparable with number of neurons in an isolated cortical gyrus; this minimum was dramatically reduced when the amplitude of miniature events was increased to model in vitro conditions. Intrathalamic RE and TC cells displayed waning spindle oscillations, which stated at the beginning of each depth negativity in the cortex. Reduction of the K+ leak current in PY and TC cells and reduction of the intracortical PY-PY and intrathalamic TC-RE-TC synaptic conductances were sufficient to eliminate the hyperpolarized phases of SWS oscillations and transform them to tonic firing at frequency 15-20 Hz. TC cells were mostly silent; however, presynaptic TC cell stimulation evoked spiking response that were reflected in cortical activity. Thus, this model captures not only the essential features of the SWS and awake states of the thalamocortical system but also the transition between them.