Astrocyte syncytium: a functional reticular system in the brain

In contrary to the discrete neuronal circuits, astrocytes share their cytoplasm through gap junctional coupling into a syncytium. This distinctive difference in neuronal and astrocytic anatomy recalls the historical debate between Camillo Golgi and Ramón y Cajal on the wiring principle of the nervous system over a century ago (Cimino, 1999). At that neuron-centric era, the Cajal advocated the cell theory that considered the nervous system to be made up of discrete individual cells. Golgi on the other hand favored the reticular theory that viewed the nervous system as a singular continuing network system. Nevertheless, regardless of the difference in their viewpoints, both theories were intended to postulate an anatomical blueprint of neural circuitry, with no attention given to neuroglia. It was until the 1950s, the distinct membrane borders between synapses were revealed by electron microscopy, which means that neurons are indeed discrete individual cells. This declared Ramón y Cajal’s cell theory the victor in the debate, while Golgi’s reticular theory was disregarded. However, the existence of a “low-resistance pathway” between neuroglia was soon identified in the optic nerve in the 1960s (Kuffler et al., 1966), which we now know to be gap junction coupling that connects the cytoplasm of astrocytes into a syncytial network. Ever since, decades of studies clearly demonstrated that syncytial coupling into the network is a most prominent feature of astrocytes and these glial networks are intimately interwoven with the neuronal circuits running across the entire central nervous system (Giaume et al., 2010). Surprisingly, the question of whether a reticular system exists in parallel with the neuronal circuits has received a little research attention to this day. Interestingly, the wiring pattern of astrocyte syncytium is reminiscent of the reticular theory postulated by Golgi. In this perspective, the “revived” use of “reticular theory” is solely dedicated to the brain reticular system established by astrocytes