Microglia are neuronal macrophages that exist within many different environments in the brain. These cells play various roles, such as fostering synaptic formation and tissue development, but their flexibility existing in healthy and diseased states remains poorly understood.
That’s why researchers from the Golub Family Professor of Stem Cell and Regenerative Biology Paola Arlotta and the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard decided to investigate how microglia alter their molecular identity to match their environment. Their work, published in the journal Nature, includes novel insights into the details of neuron-microglia communication.
The brain is organized into a series of cortical layers comprising unique cell types. Using single-cell and spatial transcriptomic profiling, researchers discovered that specific layers in the brain either enhance or distribute these microglial signals, suggesting that neurons may play a significant role in influencing microglial states.
“When they were first discovered, microglia were assumed to be simply scavengers, cleaning up cell debris and helping to fight off pathogens,” said Jeffery Stogsdill, lead author and postdoctoral researcher in the Arlotta Lab. “Now we know that microglia can interact with neurons in very sophisticated ways that can affect neuron function.”
Specifically, they noted that cells in the cerebral cortex, the brain area responsible for motor and sensory functions, influence each other to induce microglia’s quantity and molecular state. This type of communication within a “neuronal niche” suggests that microglia can work alongside different cell types and can be influenced by other cells’ directions.
“You would no longer have to treat, for instance, microglia as one blanket cell type when trying to affect the brain,” stated Stogsdill. “We can target very specific states, or we can target very specific subtypes of neurons with the ability to change specific states of microglia. It allows us to have high-level granularity.”
By changing the composition of neuronal subtypes within cortical layers, the team noticed that microglia matched the type of neurons surrounding them. To further understand this form of cell signaling, the team created a molecular atlas to outline the communication between neurons and microglia. In the future, researchers can utilize this atlas to investigate these interactions’ functional roles and possible targets for therapeutic intervention.
“We know that microglia can affect the function of the neural circuit, and now we know that neurons can recruit specific types of microglia to their neighborhood,” said senior author Arlotta, an institute member at the Broad. “It’s a fascinating idea that neurons can reshape their environment to help fine-tune their own circuit function.”