Neural circuits in the 21st century: synaptic networks of neurons and glia.

Throughout the last century, most neurophysiologists believed synaptic transmission in the brain was mediated solely by neurons. Glial cells, the most numerous cells in the brain, were primarily seen as providing support but not as actively participating in rapid neural signaling. Several recent findings indicate that this restrictive view of neural circuitry may be replaced in this century by a more inclusive one in which glia play an active role in synaptic signaling. Two very recent papers, one in Nature by Bergles et al. (1) and one in this issue of PNAS by Parpura and Hayden (2), show that two different types of glial cells are involved directly in rapid glutamate-mediated neural signaling. One glial cell type, oligodendrocyte precursor cells (OPCs), was shown to receive direct synaptic input from neurons in the hippocampus (1), and another glial cell type, astrocytes, was shown to release glutamate rapidly in response to physiological increases in intracellular calcium concentration (2). These two papers—together with earlier research showing that glia express neurotransmitter receptors, release neurotransmitter, and propagate intracellular calcium waves (see refs. 3 and 4 for recent reviews)—indicate that synaptic information flows through the nervous system via glial/neuronal networks.