Trends in Neurosciences
New roles for astrocytes: Redefining the functional architecture of the brain
Section snippets
The phylogenetic advance of the astrocyte
The relative number of astrocytes, expressed both as a proportion of total brain cell number and as a ratio to neuronal number, increases with dramatically with phylogeny and brain complexity. In the leech, a typical ganglion is composed of 25–30 neurons and only one astrocyte (Figure 1). In Caenorhabditis elegans, neurons outnumber glia by 6:1 [2], whereas astrocytes and neurons are represented in a ratio of 1:3 in the cortex of lower mammals such as rats and mice. In the human cortex, there
Astrocytes establish non-overlapping territories that define functional domains
Astrocytes typically extend between five and eight major processes, each of which ramifies into fine and essentially uniformly distributed leaflet-like appendages [11]. Unexpectedly, the elaborate and dense processes of each hippocampal astrocyte define a 3D space that is free of processes from any other astrocytes. In this way, the astrocyte defines its own anatomical domain. Only the most peripheral processes interdigitate with one another, doing so along a narrow interface within which <5%
Signal propagation among astrocytes
Having learned from neurons by classical electrophysiological methods, these same methods were eagerly applied to astrocytes. The results were somewhat boring. Astrocytes are electrically non-excitable and they respond to current injection with only passive changes in membrane potential. Their resting membrane potential is maintained at ∼ −85 mV and displays little fluctuation in response to a wide variety of stimuli 4, 18. This stability and their low input resistance is likely to reflect the
Normal and pathological manifestations of glial Ca2+ signaling in vivo
Astrocytic Ca2+ waves are mediated primarily by release of ATP and activation of purine receptors (Box 1). In cultured astrocytes, Ca2+ waves are routinely generated by electrical or mechanical stimulation, but they can also be initiated by exposure to transmitters or by removal of extracellular Ca2+. In addition, recent studies have used confocal imaging to demonstrate that astrocytes in situ can propagate long-distance Ca2+ waves. However, Ca2+ waves in slices can be generated only by intense
Transmitter release by astrocytes
One of the principal functions of astrocytes is uptake of neurotransmitters released from nerve terminals [41]. But astrocytes can also release neuroactive agents, including transmitters, eicosanoids, steroids, neuropeptides and growth factors [42]. The regulation and mechanism (or mechanisms) of astrocyte-mediated release of neuroactive compounds are for most agents poorly defined. They are also hotly debated, given their theoretical importance in brain function. Release of glutamate appears
Interactions among astrocytes, neurons and endothelial cells define the gliovascular unit
The blood–brain barrier is a diffusion barrier that impedes exchange of molecules between the two tissues. The primary seal of the blood–brain barrier is formed by endothelial tight junctions. Astrocytes enwrap the vasculature with a large number of endfeet plastered at the vessel wall (Figure 4), although their role in the blood–brain barrier is poorly defined and they are not believed to have a barrier function in the mammalian brain [49]. Several factors released by astrocytes might be
Concluding remarks
Ideas about glial function originally sprang from the anatomy of these cells. Modern researchers have gained knowledge about glial cells by studying their physiology and biochemistry in isolation from their normal cellular partners. This was necessary to avoid the confounding complexity of the intact CNS. The risk, however, is that we lose sight of the in vivo anatomical relationships of these cells, which define what their sphere of influence can be. Current evidence indicates that anatomy and
Acknowledgements
We thank Marisa Cotrina and Greg Arcuino for discussions, and Marie Simard, Takahiro Takano and Xiaohai Wang for the data illustrated in Figure 1, Figure 2, Figure 3, Figure 4. Our studies are supported by NINDS/NIH, the Brain Tumor Association, and New York State Spinal Cord Injury Research Program.
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