IONIC MECHANISMS UNDERLYING SYNCHRONIZED OSCILLATIONS AND PROPAGATINGWAVES IN A MODEL OF FERRET THALAMIC SLICES

1. A network model of thalamocortical (TC) and thalamic reticular (RE) neurons was developed based on electrophysiological measurements in f erret thalamic slices. Single-compartment TC and RE cells included vol tage- and calcium-sensitive currents de scribed by Hodgkin-Huxley type of kinetics. Synaptic currents were modeled by kinetic models of lpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), gamma-amin obutyric acid-A (GABA(A)) and GABA(B) receptors. 2. The model reproduc ed successfully the characteristics of spindle and slow bicuculline-in duced oscillations observed in vitro. The characteristics of these two types of oscillations depended on both the intrinsic properties of TC and RE cells and their pattern of interconnectivity. 3. The oscillati ons were organized by the reciprocal recruitment between TC and RE cel ls, due to their mutual connectivity and bursting properties. TC cells elicited AMPA-mediated excitatory postsynaptic potentials (EPSPs) in RE cells, whereas RE cells elicited a mixture of GABA(A) and GABA(B) i nhibitory postsynaptic potentials (IPSPs) in TC cells. Because of the presence of a T current, sufficiently strong EPSPs could elicit a burs t in RE cells, and TC cells could generate a rebound burst following G ABAergic IPSPs. Under these conditions, interaction between the TC and RE cells produced sustained oscillations. 4. In the absence of sponta neous oscillation in any cell, the TC-RE network remained quiescent. S pindle oscillations with a frequency of 9-11 Hz could be initiated by stimulation of either TC or RE neurons. A few spontaneously oscillatin g TC neurons recruited the entire network model into a ''waxing-and-wa ning'' oscillation. These ''initiator'' cells could be an extremely sm all proportion of TC cells. 5. In intracellular recordings, TC cells d isplay a reduced ability for burst firing after a sequence of bursts. The ''waning'' phase of spindles was reproduced in the network model b y assuming an activity-dependent upregulation of I-h Operating via a c alcium-binding protein in TC cells, as shown previously in a two-cell model. 6. Following the global suppression of GABA(A) inhibition, the disinhibited RE cells produced prolonged burst discharges that elicite d strong GABA(B)-mediated currents in TC cells. The enhancement of slo w IPSPs in TC cells was also due to cooperativity in the activation of GABA(B)-mediated current. These slow IPSPs recruited TC and RE cells into slower waxing-and-waning oscillations (3-4 Hz) that were even mor e highly synchronized. 7. Local axonal arborization of the TC to RE an d RE to TC projections allowed oscillations to propagate through the n etwork. An oscillation starting at a single focus induced a propagatin g wavefront as more cells were recruited progressively. The waning of the oscillation also propagated due to upregulation of I-h in TC cells , leading to waves of spindle activity as observed in experiments. 8. The spatiotemporal properties of propagating waves in the model were h ighly dependent on the intrinsic properties of TC cells. The spatial p attern of spiking activity was markedly different for spindles compare d with bicuculline-induced oscillations and depended on the rebound bu rst behavior of TC cells. The upregulation of I-h produced a refractor y period so that colliding spindle waves merged into a single oscillat ion and extinguished. Finally, reducing the I-h conductance led to sus tained oscillations. 9. Two key properties of cells in the thalamic ne twork may account for the initiation, propagation, and termination of spindle oscillations, the activity-dependent upregulation of I-h in TC cells, and the localized axonal projections between TC and RE cells. In addition, the model predicts that a nonlinear stimulus dependency o f GABA(B) responses accounts for the genesis of prolonged synchronized discharges following block of GABA(A) receptors.