Spike-and-wave oscillations based on the properties of GABA(B) receptors

Alain Destexhe

Journal of Neuroscience 18: 9099-9111, 1998

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Abstract:

Neocortical and thalamic neurons are involved in the genesis of generalized spike-and-wave (SW) epileptic seizures. The cellular mechanism of SW involves complex interactions between intrinsic neuronal firing properties and multiple types of synaptic receptors, but due to the complexity of these interactions, the exact details of this mechanism are unclear. In this paper, these types of interactions were investigated using biophysical models of thalamic and cortical neurons. It is first shown that, due to the particular activation properties of gamma-aminobutyric acid(B) (GABA(B)) receptor-mediated responses, simulated field potentials can display SW waveforms if cortical pyramidal cells and interneurons generate prolonged discharges in synchrony, without any other assumptions. Here, the ``spike'' component coincided with the synchronous firing, while the ``wave'' component was mostly generated by slow GABA(B)-mediated K+ currents. Second, the model suggests that intact thalamic circuits can be forced into a ~3 Hz oscillatory mode by corticothalamic feedback. Here again, this property was due to the characteristics of GABA(B)-mediated inhibition. Third, in the thalamocortical system, this property can lead to generalized ~3 Hz oscillations with SW field potentials. The oscillation consisted in a synchronous prolonged firing of all cell types, interleaved with a ~300 ms period of neuronal silence, similar to experimental observations during SW seizures. This model suggests that SW oscillations can arise from thalamocortical loops in which the corticothalamic feedback indirectly evokes GABA(B)-mediated inhibition in the thalamus. This mechanism is shown to be consistent with a number of different experimental models, and experiments are suggested to test its consistency.
See also the following related article:

Destexhe A. Can GABA_A conductances explain the fast oscillation frequency of absence seizures in rodents ? European Journal of Neuroscience 11: 2175-2181, 1999.


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