Glial cells aid memory formation

Neurons need non-electrical brain cells known as astrocytes to establish synaptic memory, according to study published this week in Nature. The findings challenge the long-standing belief that this process involves only the activity of the neurons themselves, and bring glial cells onto the center stage in the study of brain activity. An astrocyteImage: Wikimedia commons, NeurorockerThis study shows that while neurotransmitter release and voltage changes at the synapse are important for synapt

Jef Akst

| 3 min read

Neurons need non-electrical brain cells known as astrocytes to establish synaptic memory, according to study published this week in Nature. The findings challenge the long-standing belief that this process involves only the activity of the neurons themselves, and bring glial cells onto the center stage in the study of brain activity.

An astrocyte
Image: Wikimedia commons,
Neurorocker

This study shows that while neurotransmitter release and voltage changes at the synapse are important for synaptic memory formation, "you need the burst from the astrocyte to complete the process," said physiologist linkurl:Andrea Volterra;http://www.unil.ch/fbm/page28867_en.html of the University of Lausanne, who did not participate in the research. "It's very surprising for many people." Astrocytes comprise some 90% of all human brain cells, but because they lack the electrical activity of neurons, they were never really considered to participate in the process of long-term potentiation -- changes in synaptic strength thought to underlie learning and memory. Accumulating evidence suggests they play a bigger role in neuronal activity than previously believed. For example, astrocytes are known to experience changes in intracellular calcium concentrations that can vary as a result of neuronal activation, linkurl:which can trigger the release of neurotransmitters.;http://www.nature.com/nature/journal/v369/n6483/abs/369744a0.html By monitoring the electrical activity surrounding specific astrocytes, neuroscientist linkurl:Dmitri Rusakov;http://www.ion.ucl.ac.uk/%7Edrusakov/ of the University College London and his colleagues demonstrated that chemically clamping an astrocyte to prevent any increases in intracellular calcium stores abolished the induction of LTP around the cell. "We were testing the hypothesis that synaptic LTP induces microscopic structural changes in local astrocytes," Rusakov wrote in an email to The Scientist. "Unexpectedly, we have noticed that clamping astrocytic Ca²⁺ blocks local LTP induction altogether." LTP could be rescued, however, by introducing the amino acid D-serine -- a coagonist of the NMDA receptor (NMDAR), whose activation is necessary for the induction of LTP. Thus, increases in the intracellular calcium levels of astrocytes seem to trigger the release of D-serine, which aids the activation of NMDARs and promotes synaptic memory formation. "This is an elegant experiment to show that all the synapses in the domain of that astrocyte are controlled and need D-serine from that astrocyte [for LTP induction]," said Volterra, who wrote an accompanying review in Nature. The effect appeared to be localized, with synapses just 200 micrometers away from clamped astrocytes exhibiting normal LTP formation. But astrocytes extend only about 50 to 70 micrometers, Volterra said, suggesting that the effect was not entirely contained within the reach of the manipulated astrocyte. It could be that the intracellular effect spread via the gap junctions that connect adjacent astrocytes, thereby affecting neurons at some distance, Rusakov hypothesized. Alternatively, the local "void" of D-serine where its release was blocked may have resulted in the diffusion of D-serine from surrounding areas, thus depleting the D-serine supply in areas beyond the reach of the manipulated astrocyte. But with astrocyte territories containing many thousands of synapses (about 140,000 in the hippocampus, for example), even effects limited to those within a territory can be enormous. Thus, the role that astrocytes play in synaptic function "cannot be overlooked," Volterra noted in his review. Furthermore, these results "may have a number of implications for excitatory transmission, quite apart from the NMDAR-dependent LTP," Rusakov added. "The concept is there, but we need to do further studies to really understand the specific roles of the astrocytes," Volterra said. "This is a bit difficult because there is a very intimate communication between astrocytes and synapses [that] cannot be seen by electrical recording." Future experiments will need to combine precise electrical recordings with local calcium imaging to see the response of the astrocyte on the response of one synapse. "That's challenging methodology," Volterra said, "[but] we are developing approaches to do that."
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[25th November 2002]