Mo Costandi

Astrocytes take centre stage in brain function

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Astrocytes are a subtype of neuroglial cell found exclusively in the central nervous system. These star-shaped cells have numerous projections, outnumber neurons by up to 50:1, and are characterized by the expression of glial fibrillary acidic protein (GFAP, stained green in the image on the left).

It was always believed that astrocytes do little more than provide neurons with structural and metabolic support. The end-feet of astrocytes are closely apposed to capillaries in the brain, and transport glucose from the blood to neurons, metabolizing it en route. Astroglial end-feet are also thought to play a role in regulating the flow of blood through capillaries

However, in recent years, it has become clear that astrocytes are far more active than was previously thought, with various studies providing evidence that they are involved in modulating neuronal activity.

For example, it is now known that astrocytes synthesize and release the neurotransmitter glutamate, remove glutamate from the synaptic cleft by active transport and form synaptic connections with neurons. It also appears that networks of astrocytes form a syncytium (a large region of cytoplasm containing many cell nuclei), in which the cells are connected by electrical synapses called gap junctions that enable them to synchronize their activity.

A new study published online in the November issue of PLoS Biology now provides further evidence of the involvement of astrocytes in modulating the activity of neurons.  

Genoud et al hyperstimulated a single whisker in mice; this produces physiological and structural changes in the barrel cortex, the region of the rodent somatosensory cortex which receives and processes tactile information from the whiskers.

First,  Grenoud and her colleagues used immunohistochemical staining to show that expression levels of glutamate transporter 1 (GLT1) and glutamate aspartate transporter (GLAST) more than doubled after 24 hours of whisker stimulation, but returned to pre-stimulation levels after 4 days. In contrast, levels of another glutamate transporter expressed in neurons, excitatory amino acid carrier 1 (EAAC1), remained unchanged.

They then cut serial sections of the barrel cortex that had been activated by stimulation of the whisker, and imaged these sections with an electron microscope.  This revealed that whisker stimulation resulted in dramatic morphological changes at the interface between nerve terminals and dendritic spines. Sections of barrel cortex that had been activated by whisker stimulation were seen to contain greater numbers of dendritic spines that were completely enveloped by the processes of astrocytes than sections of cortex that were not activated. Further analyses showed that the degree of contact between nerve terminals and dendritic spines in the barrel cortex did not change in response to whisker stimulation.

The increase in astrocyte membrane encircling synapses in response to whisker stimulation probably determines the amount of glutamate uptake by the astrocytes. The electron micrograph on the left shows a dendritic spine (S) from a stimulated barrel cortex completely surrounded by the processes of an astrocyte (coloured blue and labelled with an asterisk). 

Glutamate is the principal excitatory neurotransmitter in the nervous system, and, like all other transmitters, it has to be removed from the synaptic cleft after it has been released from nerve terminals. An interruption of glutamate re-uptake can lead to abnormal, epilepsy-like electrical activity or excitotoxic damage.

It was already known that astrocyte processes are highly dynamic. These experiments, which involved chronic hyperstimulation of the barrel cortex, show that this astroglial plasticity may play an essential role in clearing excess glutamate from synapses, providing protection from over-stimulation. Furthermore, the finding that astroglial dynamics are involved in the brain’s response to changes in sensory activity implies that astrocytes may also be involved in other experience-dependent synaptic modifications.

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