Dynamic interactions determine partial thalamic quiescence in a computer
network model of spike-and-wave seizures
William W. Lytton, Diego Contreras, Alain Destexhe and Mircea Steriade
Journal of Neurophysiology 77: 1679-1696, 1997.
In vivo intracellular recording from cat thalamus and cortex was performed
during spontaneous spike-wave seizures characterized by synchronously firing
cortical neurons correlated with the electroencephalogram. During these
seizures, thalamic reticular (RE) neurons discharged with long spike bursts
riding on a depolarization, whereas thalamocortical (TC) neurons were either
entrained into the seizures (40%) or were quiescent (60%). During quiescence,
TC neurons showed phasic inhibitory postsynaptic potentials (IPSPs) that
coincided with paroxysmal depolarizing shifts in the simultaneously recorded
cortical neuron. Computer simulations of a reciprocally connected TC-RE pair
showed two major modes of TC-RE interaction. In one mode, a mutual oscillation
involved direct TC neuron excitation of the RE neuron leading to a burst that
fed back an IPSP into the TC neuron, producing a low-threshold spike. In the
other, quiescent mode, the TC neuron was subject to stronger coalescing IPSPs.
Simulated cortical stimulation could trigger a transition between the two
modes. This transition could go in either direction and was dependent on the
precise timing of the input. The transition did not always follow the
stimulation immediately. A larger, multicolumnar simulation was set up to
assess the role of the TC-RE pair in the context of extensive divergence and
convergence. The amount of TC neuron spiking generally correlated with the
strength of total inhibitory input, but large variations in the amount of
spiking could be seen. Evidence for mutual oscillation could be demonstrated
by comparing TC neuron firing with that in reciprocally connected RE neurons.
An additional mechanism for TC neuron quiescence was assessed with the use of
a cooperative model of gamma-aminobutyric acid-B (GABA(B))-mediated responses.
With this model, RE neurons receiving repeated strong excitatory input
produced TC neuron quiescence due to burst-duration-associated augmentation of
GABA(B) current. We predict the existence of spatial inhomogeneity in
apparently generalized spike-wave seizures, involving a center-surround
pattern. In the center, intense cortical and RE neuron activity would be
associated with TC neuron quiescence. In the surround, less intense
hyperpolarization of TC neurons would allow low-threshold spikes to occur.
This surround, an "epileptic penumbra," would be the forefront of the
expanding epileptic wave during the process of initial seizure generalization.
Therapeutically, we would then predict that agents that reduce TC neuron
activity would have a greater effect on seizure onset than on ongoing
spike-wave seizures or other thalamic oscillations.
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