IONIC MECHANISMS UNDERLYING SYNCHRONIZED OSCILLATIONS AND PROPAGATING WAVES
IN A MODEL OF FERRET THALAMIC SLICES.
Destexhe, Alain, Thierry Bal, David A. McCormick and Terrence J. Sejnowski.
The Howard Hughes Medical Institute and The Salk Institute, Computational
Neurobiology Laboratory, 10010 North Torrey Pines Road, La Jolla, CA 92037,
USA, Department of Physiology, Laval University School of Medicine, Quebec G1K
7P4, CANADA, Section of Neurobiology, Yale University School of Medicine, 333
Cedar Street, New Haven, CT 06510, USA, Institut Alfred Fessard, CNRS, Avenue
de la Terrasse, Gif-sur-Yvette Cedex, 91198, FRANCE, Department of Biology,
University of California San Diego La Jolla, CA 92037, USA.
APStracts 3:0073N, 1996.
SUMMARY AND CONCLUSIONS
1. A network model of thalamocortical (TC) and thalamic reticular (RE) neurons
was developed based on electrophysiological measurements in ferret thalamic
slices. Single-compartment TC and RE cells included voltage- and calcium-
sensitive currents described by Hodgkin-Huxley type of kinetics. Synaptic
currents were modeled by kinetic models of AMPA, GABA_A and GABA_B receptors.
2. The model reproduced successfully the characteristics of spindle and slow
bicuculline-induced 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 oscillations
were organized by the reciprocal recruitment between TC and RE cells, due to
their mutual connectivity and bursting properties. TC cells elicited AMPA-
mediated EPSPs in RE cells, whereas RE cells elicited a mixture of GABA_A and
GABA_B IPSPs in TC cells. Due to the presence of a T-current, sufficiently
strong EPSPs could elicit a burst in RE cells, and TC cells could generate a
rebound burst following GABAergic IPSPs. Under these conditions, interaction
between the TC and RE cells produced sustained oscillations. 4. In the absence
of spontaneous oscillation in any cell, the TC-RE network remained quiescent.
Spindle oscillations with a frequency of 9-11 Hz could be initiated by
stimulation of either TC or RE neurons. A few spontaneously oscillating TC
neurons recruited the entire network model into a ``waxing-and-waning''
oscillation. These ``initiator'' cells could be an extremely small proportion
of TC cells. 5. In intracellular recordings, TC cells display a reduced
ability for burst firing following a sequence of bursts. The ``waning'' phase
of spindles was reproduced in the network model by assuming an activity-
dependent upregulation of I_h operating via a calcium-binding protein in TC
cells, as shown previously in a 2-cell model. 6. Following the global
suppression of GABA_A inhibition, the disinhibited RE cells produced prolonged
burst discharges that elicited strong GABA_B-mediated currents in TC cells.
The enhancement of slow 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 more
highly synchronized. 7. Local axonal arborization of the TC to RE and RE to TC
projections allowed oscillations to propagate through the network. An
oscillation starting at a single focus induced a propagating wavefront as more
cells were progressively recruited. 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 highly dependent on the intrinsic
properties of TC cells. The spatial pattern of spiking activity was markedly
different for spindles compared to bicuculline-induced oscillations and
depended on the rebound burst behavior of TC cells. The upregulation of I_h
produced a refractory period so that colliding spindle waves merged into a
single oscillation and extinguished. Finally, reducing the I_h conductance led
to sustained oscillations. 9. Two key properties of cells in the thalamic
network 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 of GABA_B responses accounts for
the genesis of prolonged synchronized discharges following block of GABA_A
Received 3 January 1996; accepted in final form 28 March 1996.
APS Manuscript Number J5-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 May 96