Ionic mechanisms underlying synchronized oscillations and propagating waves in a model of ferret thalamic slices

Alain Destexhe, Thierry Bal, David A. McCormick and Terrence J. Sejnowski

Journal of Neurophysiology 76: 2049-2070, 1996

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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 receptors.


Movies:

Several movie files illustrate the oscillatory dynamics of the network of thalamic neurons. They are an excellent complement to the figures of the paper (Figs 12 and 13). The spatiotemporal distribution of activity in the network during oscillations is shown by colors.

spindle.mpg

bicuculline.mpg


Programs:

The original NEURON programs that served to simulate this model are also available. They provide a useful way to learn how to design network models using NEURON.

NEURON demo:

This package creates a directory containing a demo for running networks of thalamic neurons using the object-oriented facilities of NEURON. The simulations reproduce some of the figures of the paper, in which all the details are given. There are also instructions in the README file.

Cover:

The cover of the September 1996 issue of The Journal of Neurophysiology was chosen from the above paper.
Click here and here to see gif images of that cover picture.

Legend: The mechanisms underlying the initation, propagation and termination of thalamic oscillations were investigated using a combination of computational models (color frames) and intracellular recordings in slices (yellow traces). Top panels represent sleep spindle oscillations and their transformation into epileptic discharges is shown in bottom panels.


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