Leao's spreading depression: Synaptic regulation of a diffuse self-oscillating process in the central nervous system

The evidence reviewed in the paper shows that the spreading depression (SD) belongs to the mass of closely packed neurons which can support qualitatively new phenomena occurring at a more primitive level of cellular interaction. The latter becomes prepotent under extreme conditions, overloading the local energy supply and homeostatic mechanisms. The two levels of neural integration, the highly heterogeneous specifically connected synaptic level and the statistically uniform diffusively organized nonsynaptic level, are always present in all forms of brain activity and mutually influence each other. While phenomena mediated by nonsynaptic interaction overrule the synaptic ones under resting conditions, excessive synaptic excitation may either switch the affected brain region from synaptic to nonsynaptic interaction (spike-triggered SD) or assert the synaptic interaction over the nonsynaptic one (functional blockade of SD). Nonsynaptic interaction is an inherent property of brain, an obligatory consequence of the trade-off between maximal packing density and independent function of individual elements of the system which sets definite limits to the maximum activation of synaptic processes, contributes to slow synchronization of neural populations and plays an important role in various instances of brain pathology. The phenomena generated at this level belong to the family of autowaves, share their typical properties and can be described by similar formal rules.