Abstracts

RATIONALE: The interruption of a focal and chronic infusion of [gamma]-aminobutyric acid (GABA) in the neocortex of rats gives rise to the progressive emergence of a sustained spikes activity, associated with myoclonic jerks of the corresponding body territory. This activity remains for hours at an average frequency of 1.5 Hz and is localized to the previous site of infusion. The GABA withdrawal syndrome (GWS) has therefore features of partial status epilepticus.
The changes of neural interactions were studied in living rats by measuring the phase synchrony between epidural electroencephalographic signals bilaterally recorded in the neocortex.
METHODS: Nineteen adult rats were stereotactically implanted with a stainless steel cannula in the left somatomotor cortex. The cannula was connected, via a subcutaneous catheter, to an osmotic minipump placed under the skin of the rat[ssquote]s back, and filled with a Kreb[ssquote]s solution containing GABA (1 M). The infusion was delivered at a rate of 1 [mu]l/h during 5 days, then was interrupted.
The analysis of phase synchrony between neuronal signals measured the degree to which two signals were phase-locked during a short period of time, and was performed as previously described (Le Van Quyen et al., 2001 J Clin Neurophysiol 18 : 191-208).The level of phase synchrony between EEG signals was measured from 0.1 to 200 Hz by steps of 2 Hz, then in specific frequency bands.
Spectral analysis was performed using the fast Fourier transform.
RESULTS: Our results showed (i) the epileptic activity was strikingly associated with a decrease of phase synchrony that largely predominated in the 1-6 Hz frequency range and for all pairs of electrodes coupled to the focus (with a mean decrease of 75 % between the synchrony levels before GABA interruption and after appearance of the epileptic activity), (ii) the GWS-related hyposynchrony was not correlated with a difference of spectral emission, since an increase of power spectrum was observed in the signals in this frequency range, (iii) no specific synchrony change was detected before the first spikes, (iiii) systemic injection of ketamine, an antagonist of the glutamatergic NMDA receptors slightly delayed the appearance of the epileptic activity if injected simultaneously to the GABA interruption, or slightly decreased the epileptic activity if later injected. In both conditions, a large frequency band decrease of synchrony was initially observed, then followed by an increase of 1-6 Hz synchrony in spite of reappearance of a spiking activity. (iiiii) Spiking activity and GWS-related synchrony changes were rapidly corrected by local reperfusion of GABA.
CONCLUSIONS: These results may suggest mechanisms underlying partial status epilepticus, and may explain why and how the epileptic activity of the focus is not able to diffuse into the whole brain and to be generalized.
Prolonged hyposynchrony between neuronal populations may favor the development of pathological, epileptic activities.
[Supported by: INSERM, FRM]