title: Dynamic interactions determine partial thalamic quiescence in a computer network model of spike-and-wave seizures.
abstract: 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.
authors.affiliation: Department of Neurology, University of Wisconsin, William S. Middleton Veterans Affairs Hospital, Madison 53706, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Lytton
authors.forename: D
authors.initials: D
authors.lastname: Contreras
authors.forename: A
authors.initials: A
authors.lastname: Destexhe
authors.forename: M
authors.initials: M
authors.lastname: Steriade
mesh_terms: D000200:Action Potentials; D000818:Animals; D002415:Cats; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D003198:Computer Simulation; D004569:Electroencephalography; D016571:Neural Networks, Computer; D009474:Neurons / Q000502:physiology*; D012154:Reticular Formation / Q000166:cytology / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology; D013788:Thalamus / Q000166:cytology / Q000502:physiology*