Per Aspera Ad Astra: signaling within tripartite synapses between dendritic spines, astrocytes and presynaptic terminals
Leonard Khirug
Research abstract
It is becoming increasingly apparent that, in addition to presynaptic terminals and postsynaptic dendritic spines, synapses contain a third element: the fine processes of the astrocyte which intimately enwrap the first two elements. Being at this location allows astrocytes to take care of extracellular ion homeostasis, provide metabolites to neurons and remove excessive neurotransmitter, the classical glial cell functions which have long been appreciated. More recently we learned that this location also enables astrocytes to carefully monitor the level of synaptic activity, "translate" it into their own language of intracellular Ca2+ signaling, and then "talk back" by releasing neuroactive substances such as ATP or glutamate. In addition, astrocytes can rapidly change the shape of their fine processes, thus causing dendritic spine retraction or enlargement, as well as dramatically affecting the degree to which the content of synaptic cleft "spills over" to the neighboring synapses or reaches extrasynaptic receptors.
If astrocytes indeed are to be considered an active partner and an equally bright star in the synaptic constellation, why have these glial cells been overlooked and considered somewhat unimportant for so long? Two possible reasons lay in the morphology and electrophysiology of glia which makes them very different from neurons. First, glial cells do not send long projections across brain regions or to the periphery of the body. Second, they do not generate action potentials and have therefore been termed electrically non-excitable. They do, however, possess a different kind of excitability which can be called chemical and consists of intracellular Ca2+ elevations, oscillations and waves. Ca2+ waves can also cross the cell boundaries and propagate over the glial networks. Sadly for glia (and quite unfortunately for brain scientists, as it turns out) this complex and finely tuned chemical signaling could not be studied until about 15-20 years ago when Ca2+ imaging methods became available.
Do glial cells actively participate in information processing in the brain? The answer is probably yes. Astrocytes are strategically positioned and perfectly equipped to exert bidirectional communication with synapses, and glial networks are heavily intertwined with the neuronal ones with which they are in constant complimentary interaction. In my talk, I will review some key molecular and cellular aspects of glial-neuronal communication, in an attempt to draw the attention of the brain studying community to the emerging necessity of including glial-neuronal signaling in their thinking about synaptic transmission, network activity, plasticity and information processing in the central nervous system.
Related articles:
1. Newmann (2003) TiNS 26:536
2. Ransom et al (2003) TiNS 26:520 and other articles from the same issue
3. the August 2004 Issue of Glia
- Zhang Q. and Haydon P. G. (2005) Roles for gliotransmission in the nervous system. Journal of Neural Transmission, 112: 121-125
- Kast B (2001) The best supporting actors. Nature 412: 674-676
- Newman Eric A. and Volterra Andrea (2004) Glial Control Of Synaptic Function GLIA 47:207-208
- Fiacco Todd A. and McCarthy Ken D.(2004) Intracellular Astrocyte Calcium Waves In Situ Increase the Frequency of Spontaneous AMPA Receptor Currents in CA1
- Pyramidal Neurons. The Journal of Neuroscience, January 21, 24(3):722-732