Spike-and-wave oscillations based on the properties of GABA(B) receptors
Alain Destexhe
Journal of Neuroscience 18: 9099-9111, 1998
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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