Stellar diversity: Neighbourly neurons control astrocyte cell types in the adult brain

A study recently published in Science reveals that the physiological features of astrocytes are actively determined by nearby neurons in the adult brain through sonic hedgehog (Shh) signalling.

Astrocytes, star-shaped cells that support almost every aspect of brain function, were previously thought to be physiologically hardwired during development. The research presented in this paper shows that astrocytes in the adult brain require cues from neurons to drive and sustain their specialised properties.

The study’s senior author Dr Keith Murai, Director of the Centre for Research in Neuroscience at McGill University Health Centre, said: “We have now discovered that astrocytes are actually incredibly flexible and potentially modifiable, which enables them to improve brain function or restore lost potential caused by disease.’’

Mammalian brains contain a wide variety of astrocytes, so to investigate how the functional profile of astrocytes continues to be shaped in the adult brain the research team focused on the cerebellar cortex that possesses just two types of astrocyte: Bergmann glial cells (BGs) and velate astrocytes (VAs). BGs enclose impulse-receiving regions of Purkinje cell neurons (PCs) while VAs surround granule cell neurons (GCs).

By searching for gene products of neurons and astrocytes in the adult brain, the researchers identified Shh signalling as a potential pathway for modulating astrocyte identity in the adult brain. Shh has previously been recognized as an important factor in embryonic development and brain morphogenesis. The pathway was thought to close down in the brain after development, but it continues to be active in the adult brain.

The researchers found that PCs in the cerebellum produced Shh protein and that Shh receptors were abundant in BGs, but not VAs. Experiments showed that BGs required Shh to maintain their physiological function. Furthermore, in transgenic models where Shh production was turned off in PCs or BGs ability to identify Shh, the BGs transcription profiles changed to one more similar to VAs. Additionally, If Shh signalling in VAs was enhanced, they became similar to BGs.

“This is an extraordinary mechanism in the healthy, mature brain that creates diversity of brain cells,’’ says Dr Murai. “Now, our goal is to see how this mechanism is affected in different brain diseases and determine if it can be harnessed to protect neurons and ultimately preserve brain function.’’

In this study, cell visualisation and electrophysiological recordings were performed on a custom built two-photon microscope assembled around a SliceScope frame with four MicroStar motorised micromanipulators. ScanImage was used for two-photon data acquisition, and electrophysiology data was collected with homemade software.

Paper reference:

Farmer W. T., Abrahamsson T., Chierzi S., Lui C., Zaelzer C., Jones E. V., Bally B. P., Chen G. G., Théroux J. F., Peng J., Bourque C. W., Charron F., Ernst C., Sjöström P. J., Murai K. K. Neurons diversify astrocytes in the adult brain through sonic hedgehog signalling Science (2016) doi: 10.1126/science.aab3103.aab3103

Banner image credit: Todd Farmer/MUHC