How Microglia Are Prompted to Change Their State to Adapt to Different Areas of the Brain - Neuroscience News

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Summary: Microglia cells listen to neighboring neurons and change their shape to match them.

One of the remaining, most fundamental questions in neuroscience asks how cells in the brain move, interact, and coordinate with each other to produce these activities.

The paper, published Wednesday, shows that microglia cells “listen in” to neighboring neurons and change their molecular state to match them.

“Now we know that microglia can interact with neurons in very sophisticated ways that can affect neuron function.”.

This discovery could one day open the door for lines of research that can target the communications between microglia and their neuron partners with pinpoint accuracy (disorders like autism and schizophrenia arise when these communications between cells go awry).

“What we’re discovering here are the rules by which different cell types in the brain talk to each other and influence each other to ultimately be able to do more together,” said senior author Arlotta, an institute member at the Broad.

The group found that during the formation of the cerebral cortex—a part of the brain responsible for skilled motor function, sensory perception, and congnition—different types of neurons influence the number and molecular state of nearby microglia in their own unique ways.

“These different types of cortical neurons recruit different numbers of microglia,” Stogsdill said.

The cerebral cortex is organized into layers with different neuron types residing in each one.

The team then changed the composition of neuron types in these layers and found that they could influence the distribution of the different microglial states.

The microglia matched the types of neurons in the new locations, confirming that the neurons were influencing them.

The team analyzed their profiling data to find pairs of interacting proteins expressed by the different microglial states and their neuron partners.

“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,” Arlotta said.

Pyramidal neuron subtype diversity governs microglia states in the neocortex

Here, using the mouse somatosensory cortex, we demonstrate that microglia density and molecular state acquisition are determined by the local composition of pyramidal neuron classes

Notably, conversion of deep-layer pyramidal neurons to an alternate class identity reconfigures the distribution of local, layer-enriched homeostatic microglia to match the new neuronal niche

Leveraging the transcriptional diversity of pyramidal neurons in the neocortex, we construct a ligand–receptor atlas describing interactions between individual pyramidal neuron subtypes and microglia states, revealing rules of neuron–microglia communication