Stores, Channels, Glue, and Trees: Active Glial and Active Dendritic Physiology

Glial cells and neuronal dendrites were historically assumed to be passive structures that play only supportive physiological roles, with no active contribution to information processing in the central nervous system. Research spanning the past few decades has clearly established this assumption to be far from physiological realities. Whereas the discovery of active channel conductances and their localized plasticity was the turning point for dendritic structures, the demonstration that glial cells release transmitter molecules and communicate across the neuroglia syncytium through calcium wave propagation constituted path-breaking discoveries for glial cell physiology. An additional commonality between these two structures is the ability of calcium stores within their endoplasmic reticulum (ER) to support active propagation of calcium waves, which play crucial roles in the spatiotemporal integration of information within and across cells. Although there have been several demonstrations of regulatory roles of glial cells and dendritic structures in achieving common physiological goals such as information propagation and adaptability through plasticity, studies assessing physiological interactions between these two active structures have been few and far. This lacuna is especially striking given the strong connectivity that is known to exist between these two structures through several complex and tightly intercoupled mechanisms that also recruit their respective ER structures. In this review, we present brief overviews of the parallel literatures on active dendrites and active glial physiology and make a strong case for future studies to directly assess the strong interactions between these two structures in regulating physiology and pathophysiology of the brain.