4. General Conclusion

In contrast to the obsolete ideas that, during slow-wave sleep, there is a global resting in cortex, neurons in neocortical areas display unexpectedly high levels of spontaneous activity and the intracortical dialogue is maintained. The slow oscillation during slow-wave sleep is initiated, maintained, and terminated through the interplay of intrinsic currents and synaptic interaction. Thus, this slow oscillation represents a spontaneous event during which cortical neurons are alternated between silent and active states for a fraction of a second. This striking change in neuronal activity and excitability involve most of the cortex and repeats hundreds of times during a sleep episode. The active and silent states are accompanied with changes in extracellular correlation of endogenous ions. The modulation of extracellular concentration of certain ions affects the intrinsic and synaptic activity. As it is mentioned above in this thesis, the Ca2+ modulation during slow oscillation has a major impact on behavior and responsiveness of these neurons in both intrinsic and synaptic levels. The change of [Ca2+]o has an opposite effect on the intrinsic and synaptic neuronal responses. At synaptic level, the increase of [Ca2+]o provoke an increase in synaptic efficiency and a decrease of [Ca2+]o leads to a decrease in synaptic efficiency due to Ca2+ effects on release probability (Crochet et al., 2005). In contrast, the increase of [Ca2+]o leads an decrease in intrinsic excitability and the decrease of [Ca2+]o results in an increase in intrinsic excitability, via Ca2+ effects on Ca2+-activated K+ conductance and its impact on spike AHP (see chapter II). Thus, under physiological conditions, where the level of synaptic activity can change quickly, modulation of somatic voltage-gated conductances may be a potent mechanism to regulate excitability.

The modulation of extracellular concentration of ions has also the impact during paroxysmal activity; this modulation mediates the switch from normal activity to paroxysmal fast activity and within paroxysmal discharges from spike-wave complexes to runs of fast spikes. The decrease in [Ca2+]o during seizures (Heinemann et al., 1977; Amzica et al., 2002) has decreases the long-range synchronization between different cortical foci via reduction of synaptic efficiency, but enhances intrinsic excitability, which help to maintain paroxysmal network excitability. Thus paroxysmal activity is characterized by large amplitude PDSs containing a significant intrinsic component (Timofeev et al., 2004) and loose synchrony (see chapter III) because the synaptic excitability was impaired.

Finally, most of electrophysiological studies address issues of (i) intrinsic neuronal mechanisms, (ii) synaptic interactions and (iii) network phenomena. However, multiple extracellular factors such as fluctuation of endogenous ion concentration or effects of extracellular field potentials produced by neighboring neuronal pulls are often ignored. Considering these factors in the understanding of brain functions would often provide missing links mediating cellular mechanisms of normal and paroxysmal brain activity.

© Soufiane Boucetta, 2005