Once believed to only behave as a supportive crutch to neurons in the central nervous system, star-shaped brain cells called astrocytes are constantly surprising researchers as their ever-increasing number of roles within the brain emerge. An interesting new mouse study, published in the journal Neuron, set out to shed novel information on the communication between neurons and astrocytes within a specific neuronal network. Intriguingly, the results they gathered suggested that in contrast to other brain areas previously investigated, the astrocytes within this particular circuit are not constantly tuned in to neuronal activities; instead they react only during large bursts of neuronal activity. 

Astrocytes are the most abundant cell type in the brain, outnumbering neurons 10-50:1. When they were first discovered, scientists believed that they only represented a passive support scaffold for the more well-known signaling cells- the neurons. But as researchers dug deeper, it became apparent that they are actually very active members of the brain cell community.

The known roles of astrocytes are diverse; they mop up excess neuronal signaling molecules (neurotransmitters) to prevent damage caused by over-excitation, they can stimulate neurons by secreting signaling molecules, and they can regulate cerebral blood flow, to name just a few. Astrocytes also envelop connections where information flows between neurons, called synapses, forming something that is called the tripartite synapse. They respond to the release of transmitters from excited neurons, which can in turn result in the astrocytes releasing their own transmitters called gliotransmitters. What is also evident is that upon neuronal excitation, adjacent astrocytes also release pools of calcium which can then spread to neighboring astrocytes. This is called a calcium wave.

Although the cellular roles for calcium are well documented, little is known about astrocytic calcium signalling in brain function. This mystery intrigued a team of scientists from the University of California, Los Angeles. Specifically, they wanted to know when the increase in astrocytic calcium occurs in response to neuronal activity. They investigated this using genetically encoded calcium (Ca²⁺) indicators, allowing the team to image calcium throughout the entire cell.

The researchers specifically wanted to investigate Ca²⁺ signalling within mature neuronal circuits, and they chose the mossy fiber pathway. This connects two areas of the hippocampus, which is a part of the brain involved in learning and memory. They stimulated the neurons which caused them to release neurotransmitters, and awaited a response in the neighboring astrocytes. Cellular Ca²⁺ release causes a rapid increase in fluorescence in this system, and they found that two neurotransmitters, glutamate and GABA, evoked this response. What they also found was that Ca²⁺ levels only increased throughout the entire astrocyte when there was a large burst of neuronal activity, i.e. when large amounts of transmitter were released.

This suggested that the astrocytes within this particular circuit may act as a switch, responding to high levels of neuronal activity but not the constant low level communication that also occurs.

These results differ from previous studies that investigated other areas of the brain, which therefore may hint that astrocytes play different roles across the brain, dependent on the area they are functioning within.

Lead researcher Dr. Khakh, UCLA, said in a press release “The next big question becomes, what do they do with that calcium?”