Brains are made of more than a tangled net of neurons. Star-like cells called astrocytes diligently fill in the gaps between neural nets, each wrapping itself around thousands of neuronal connections called synapses. This arrangement gives each individual astrocyte an intricate, sponge-like structure.
New research finds that astrocytes are much more than neurons' entourage. Their unique architecture is also extremely important for regulating the development and function of synapses in the brain.
When they don't work right, astrocyte dysfunction may underlie neuronal problems observed in devastating diseases like autism, schizophrenia and epilepsy.
The team identified a family of three proteins that control the web-like structure of each astrocyte as it grows and encases neuronal structures such as synapses. Switching off one of these proteins not only limited the complexity of the astrocytes, but also altered the nature of the synapses between neurons they touched, shifting the delicate balance between excitatory and inhibitory neural connections.
"We found that astrocytes' shape and their interactions with synapses are fundamentally important for brain function and can be linked to diseases in a way that people have neglected until now," said the senior author. The research was published in the journal Nature.
But the complexity of astrocytes is dependent on their neuronal companions. Grow astrocytes and neurons together in a dish, and the astrocytes will form intricate star-shaped structures. Grow them alone, or with other types of cells, and they come out stunted.
To find out how neurons influence astrocyte shape, a graduate student, grew the two cells together while tweaking neurons' cellular signaling mechanisms. When the neurons are killed, but preserved their structure as a scaffold, the astrocytes still beautifully elaborated on them.
"It didn't matter if the neurons were dead or alive -- either way, contact between astrocytes and neurons allowed the astrocyte to become complex," student said. "That told us that there are interactions between the cell surfaces that are regulating the process."
Searching genetic databases for cell surface proteins known to be expressed by astrocytes, three candidates that might help direct their shape showed up. These proteins, called neuroligins, play a role in building neural synapses and have been linked to diseases like autism and schizophrenia. Previously, their functions had been primarily studied in neurons.
To find out what role neuroligins play in astrocytes, the student tinkered with astrocytes' ability to produce these proteins and found that when the production of neuroligins was switched off, the astrocytes grew small and blunt and when boosted, astrocytes grew to nearly twice the size.
"The shape of the astrocytes was directly proportional to their expression of the neuroligins," the student said.
Tweaking the expression of neuroligins didn't just change the size and shape of the astrocytes. They also had a drastic effect on the synapses that astrocyte touched.
When a single neuroligin , neuroligin 2 was switched off -- the number of excitatory or "go" synapses dropped by 50 percent. The number of inhibitory or "stop" synapses stayed the same, but their activity increased.
"We are learning now that one of the hallmarks of neurological disorders like schizophrenia, autism and epilepsy is an imbalance between excitation and inhibition," student said. "Which just drives home that these disease-associated molecules are potentially functioning in astrocytes to shift this balance."