Astrocytes Shown to be Active Players in Brain’s Intelligence

Astrocytes, star shaped glial cells in the central nervous system, were thought to be primarily involved in metabolic and developmental affairs. Now researchers from the Max Planck Institute of Neurobiology in Planegg, Germany have shown that astrocytes participate in the information exchange within the brain, affecting how nerve cells signal each other.

By removing the glutamate transmitter from the synaptic gap via so-called transporters, astrocytes regulate the availability of glutamate. “These transporters are somewhat like small vacuum cleaners”, says Ruediger Klein, the supervisor of the study. “They suck surplus glutamate from the gap, which prevents, for example, glutamate spilling over from one synapse to the next.” The existence of this “glutamate vacuum cleaner” was already known to science. So far unheard of, and now shown by the scientists, was that the astrocyte and downstream nerve cell communicate with each other and thus regulate the number of glutamate-eliminating transporters.
This communication was found while the neurobiologists were examining the signaling molecule ephrinA3 and its binding partner EphA4 in mice. Ephrins and Eph-receptors are regularly involved when cells recognize or influence each other. Astrocytes, for example, promote synapse maturation via ephrinA3/EphA4 interaction. “Yet it came as a surprise to find an effect working also in the other direction”, Ruediger Klein remembers. The scientists found that if a nerve cell is lacking the EphA4-receptor, the neighboring astrocyte increases its transporter numbers. The resulting superabundant transporters eliminate so much glutamate from the synapse that its strengthening becomes impossible, a sure disadvantage for the ability to learn.
The importance of the ephrinA3/EphA4 signaling pathway was further emphasized by the control studies. If the signaling molecule ephrinA3 was absent in an astrocyte, a synaptic strengthening was impaired due to the lack of glutamate – just what happened when EphA4 was missing. In contrast, if ephrinA3 was experimentally increased, the number of astrocyte-transporters decreased. As a result glutamate accumulated in the synaptic gap which in turn quickly led to cell damages and malfunctions of the affected synapses.
“We are currently investigating the mechanisms through which ephrinA3/EphA4 affect the transporter production”, explains Ruediger Klein. The scientists’ aim is to better understand the transporters’ function. An important task, as malfunctioning of the astrocyte transporters is known to play a role in neurological and neurodegenerative diseases such as epilepsy and the amyotrophic lateral sclerosis (ALS).

Side image: Some contact points between nerve cells (red) are surrounded by star-shaped cells known as astrocytes (green).
Press release: Star-shaped cells in the brain aid with learning…
Full article in Nature Neuroscience: Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport