In addition to neurons the brain contains 3 types of glial cells. Astrocytes account for one quarter of the total volume of brain cortex, but oligodendrocytes and microglia are also present. In white matter oligodendrocytes and myelination are of key importance, but oligodendrocytic-astrocytic interactions also occur. More is known about astrocytic biology than about that of other glial cell types. One of the most important functions of astrocytes is to provide neurons with all glutamate and GABA needed for neurotransmission, since neurons themselves lack the enzymes necessary for the synthesis of these amino acid transmitters from glucose. This may be the major reason that it has been convincingly shown in several laboratories in both rat and human brain in vivo that astrocytes have rates of oxidative metabolism and expressions of enzymes involved in oxidative metabolism that are at least as high as those in neurons, suggesting important energy-requiring functions. One such function is memory, which is dependent on glutamate formation, activation of several different transmitters and on glycogenolysis, an astrocyte-specific process. The dependence on glycogenolysis was first shown by Marie Gibbs for one-trial aversive learning in the day-old chick, triggered by incoming neuronal stimuli, perhaps acting on 5-HT2B receptors. She studied the stage(s) of memory formation prior to protein formation and could show that glutamate formation and probably also Na+,K+-ATPase function (and thus K+ homeostasis) depended on glycogenolysis. Dependence of learning on glycogenolysis has repeatedly been confirmed in mammals and been found to include long-term protein synthesis-dependent memory and even changes in neuronal electrophysiology, e.g. LTP. There may be many reasons for astrocytic effects on neuronal plasticity, including Ca2+-dependent release of ‘gliotransmitters’ such as ATP and glutamate from astrocytes and transmitter effects on astrocytes leading to transactivation of the epidermal growth factor (EGF) receptor by release of growth factor(s) that affect both astrocytes and neurons. Another reason is that astrocytes exert essential maturational effects on neurons and on synapse formation during development. Recent research indicates that besides astrocytes microglia is involved in interactions with neurons, in many cases by microglial effects on astrocytes leading to subsequent neuronal effects. For this reason low concentrations of cytokines released by microglia and/or astrocytes support the establishment of memory. However, learning is also dependent on white matter, where axonal conduction is facilitated by oligodendrocyte-mediated myelination. Myelin makes up a large fraction of brain dry matter, increases in amount during a long developmental period during which increased myelination develops in parallel with reasoning ability. Moreover, training of specific pathways leads to enhanced myelination, a process, which may also be important in Pavlovian conditioning. K+-mediated facilitation of learning may be associated with excitation-induced K+ release and re-uptake. Thus, processes initiated by neuronal activity lead to a multitude of responses in astrocytes, microglia and oligodendrocytes which are essential for the ability to remember the events initiating these processes. Some details of these are known, other, including most subsequent interactions with neurons remain to be further established.

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.