The role of non-synaptic extracellular glutamate

Although there are some mechanisms which allow the direct crossing of substances between the cytoplasm of adjacent cells (gap junctions), most substances use the extracellular space to diffuse between brain cells. The present work reviews the behavior and functions of extracellular glutamate (GLU). There are two extracellular pools of glutamate (GLU) in the brain, a synaptic pool whose functions in the excitatory neurotransmission has been widely studied and an extrasynaptic GLU pool although less known nonetheless is gaining attention among a growing number of researchers. Evidence accumulated over the last years shows a number of mechanisms capable of releasing glial GLU to the extracellular medium, thus modulating neurons, microglia and oligodendrocytes, and regulating the immune response, cerebral blood flow, neuronal synchronization and other brain functions. This new scenario is expanding present knowledge regarding the role of GLU in the brain under different physiological and pathological conditions. This article is part of a Special Issue entitled 'Extrasynaptic ionotropic receptors'.