03 Sep 2004

Biological synchrony, be it the contraction of heart muscles or the flashing of firefly lanterns, almost always reflects some fundamentally important physiology. In yesterday’s Neuron, Giorgio Carmignoto and colleagues at the University of Padoza, Italy, and the University of Pennsylvania School of Medicine, Philadelphia, report that glia induce synchronous inward electrical currents in hippocampal neurons. The finding indicates that the function of glia-to-neuron transmission, though as yet unclear, may nonetheless be more than just “white noise.” It also raises questions about the possible role of glia in neural networks, particularly in the hippocampus, one of the regions hardest hit by neurodegeneration in Alzheimer disease.

When first author Tomasso Fellin and colleagues measured currents evoked by repeated stimulation of neurons in hippocampal slices (a commonly used technique to measure long term potentiation, a phenomenon considered by many to be at the heart of learning and memory; see ARF related news story and alternative views), they found that in addition to the normal post-synaptic currents, they could also detect slow inward currents that occurred at low frequency and had very different characteristics (slower rise times, different amplitudes). By repeating these experiments with hippocampal slices soaked in various receptor agonists and antagonists, the authors were able to show that the slow inward currents, or SICs, were caused by stimulation of N-methyl-D-aspartate-type glutamate receptors. Significantly, the SICs occurred even if the slices were incubated with tetanus neurotoxin, which blocks the synaptic release of neurotransmitters, suggesting that the source of the glutamate was not neuronal. So where was it coming from?

One clue Fellin found was that SICs were triggered by stimuli that evoke release of calcium in astrocytes. To test if astrocytes were indeed the source of the glutamate, the authors used a “cage” to trap calcium within these glia. Because the cage, a light-sensitive chelator, can be opened with a laser, Fellin and colleagues were able to selectively release calcium one astrocyte at a time. When they did this, they found that SICs were induced in adjacent neurons only, indicating that astrocytes are indeed the source of the glutamate.

But even more remarkable was the finding that stimulation of astrocytes results in the synchronous stimulation of several adjacent neurons. Recordings from pyramidal neurons, for example, showed that stimulation of astrocytes resulted in temporally correlated SICs in different neurons.

The role of synchronous SICs is unclear, but “its very presence raises a series of questions on its possible role in pathological changes in the hippocampus, such as excitotoxic neuronal damage or the generation of epileptiform activity,” state the authors.

Glia have long been thought of as housekeepers of the central nervous system. Only recently was it realized that glutamate from astrocytes can modulate neuronal transmission (see, for example, Kang et al., 1998). In the present study, Fellin and colleagues found that the NMDA receptor being stimulated was the NR1/NR2B variety, which is found mainly in extrasynaptic membranes.—Tom Fagan

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References

News Citations

1. LTP and Memory Effects May Be the First Casualties in AD 8 Jul 2003
2. The AMPA Receptor Steps out of the Shadows 22 Nov 2002

Paper Citations

1. Kang J, Jiang L, Goldman SA, Nedergaard M. Astrocyte-mediated potentiation of inhibitory synaptic transmission. Nat Neurosci. 1998 Dec;1(8):683-92. PubMed.

Further Reading

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