Astrocyte · Grey Matter

An astrocyte is a star-shaped glial cell that keeps the space around neurons fit for signalling: it clears the glutamate released at synapses, soaks up the potassium that firing neurons leave behind, and links active tissue to its blood and energy supply.

Astrocyte. An astrocyte is a star-shaped glial cell that keeps the space around neurons fit for signalling: it clears the glutamate released at synapses, soaks up the potassium that firing neurons leave behind, and links active tissue to its blood and energy supply.

Each astrocyte covers its own territory, and its fine processes wrap thousands of synapses and touch the walls of nearby capillaries. Two of its jobs matter directly for excitability. The first is glutamate uptake: transporters on the astrocyte membrane (GLT-1 carries most of it in the adult forebrain, GLAST the rest) pull glutamate out of the cleft and the surrounding space, and the astrocyte converts it to glutamine and hands it back to neurons to be made into transmitter again. The second is potassium buffering: every spike releases potassium into a narrow extracellular space, and astrocytes take it up through their own potassium channels and redistribute it through the network of coupled astrocytes, a mechanism called spatial buffering.

The transporters run on the sodium gradient, so clearing glutamate costs the astrocyte its own pump work and ATP; the uptake machinery sits next to the pumps and the mitochondria in the same fine processes.

When either job falls behind, the tissue becomes easier to excite. Raised extracellular potassium depolarises every neuron nearby, and lingering glutamate keeps receptors open; altered astrocyte transporters are a common finding in epileptic tissue and seizure models.

Astrocytes also swell as they take up potassium and water, shrinking the extracellular space, which concentrates whatever is left in it.

The astrocyte is the housekeeper that decides how long a signal lingers.

Excitability depends on how fast the leftovers of firing are removed as much as on the firing itself.

Questions: Do astrocytes feed neurons with lactate? Partly, and how much is debated. Pellerin and Magistretti proposed in 1994 that glutamate uptake makes astrocytes speed up glycolysis and export lactate, which neurons then oxidise, a neat link between synaptic activity and fuel delivery. Lactate transporters on both cells and animal studies in which astrocytic lactate supports memory consolidation back a role for it. Critics point out that neurons also take up and use glucose directly during activity, and that the measured fluxes do not add up to astrocytes supplying most neuronal energy, so the shuttle is best treated as a real but contested contribution. What does the potassium that astrocytes buffer have to do with spreading depression? Every spike leaves potassium in the narrow space between cells, and astrocytes normally take it up and spread it through their coupled network. If potassium and glutamate accumulate faster than astrocytes and pumps can clear them, the local neurons depolarise, release still more of both, and the tissue can cross into a self-sustaining collapse of the gradients. Spreading depression is that collapse travelling: the potassium and glutamate released at the front depolarise the next patch of cortex, and the wave advances at a few millimetres per minute. How easily a cortex supports such a wave depends in part on how well its astrocytes keep the extracellular space clean. What does the blood-brain barrier let through, and which cells build it? The barrier itself is the endothelial cells of brain capillaries, sealed to one another by tight junctions built mainly of claudin-5; pericytes on the capillary wall and the end-feet of astrocytes that cover it induce and maintain those properties. Gases and small fat-soluble molecules (oxygen, carbon dioxide, alcohol, many anaesthetics) diffuse through the cells. Nutrients cross on dedicated carriers, glucose on GLUT1 and large neutral amino acids on LAT1, while efflux pumps such as P-glycoprotein push many drugs back into the blood. Charged molecules, proteins and most medicines are kept out, which protects the neurons' environment and makes the brain hard to treat. What removes glutamate after it is released, and why does the speed matter? There is no enzyme that destroys glutamate in the cleft; it is pumped away, mostly into astrocytes, whose transporters (GLT-1 carries about 90 % of the uptake in the adult forebrain) sit on the fine processes wrapped around synapses. The astrocyte turns it into glutamine and returns that to neurons to be made into transmitter again. Fast clearance keeps each signal short and private to its synapse; when uptake slows, glutamate lingers, spills to neighbouring synapses and keeps receptors open, and altered astrocyte transporters are a common finding in epileptic tissue. Why does a rise of potassium outside the cells make every neuron nearby easier to fire? The resting voltage is set mainly by the potassium gradient, so it depends on the ratio of potassium inside to potassium outside. Outside, potassium is only a few millimolar, so adding a few more millimolar changes that ratio a lot and moves every neuron's resting voltage upward, closer to threshold, all at once. Intense firing releases potassium into the narrow extracellular space faster than pumps can take it back, and astrocytes normally soak it up and spread it through their coupled network. When they fall behind, the extra potassium depolarises the whole neighbourhood, which raises excitability and, at high levels, can start a spreading depolarisation.