Microglia “Embrace” Aids in Synapse Formation

Researchers at Cold Spring Harbor Laboratory have discovered that immune cells in the brain that clear waste material and unneeded synapses can also help neurons grow synapses, thus playing a key role in cognitive development and functioning.

“Most immune cells are known to target and eat—let’s call it garbage,” says Cold Spring Harbor Laboratory (CSHL) Professor Linda Van Aelst.  “But what we saw is the opposite. During a particular developmental time point, under normal physiological conditions, they did not eat any synapses that we saw, but helped the synapses form. That was quite a nice surprise.”

Van Aelst’s obsession with a rare type of inhibitory neuron called a chandelier cell sparked her interest in the neural immune cells in question, called microglia. Chandelier cells are named for the ornate branching shape of their nerve fibers. These structures make direct contact with the axonal initial segment (AIS) section of a target neuron, setting off its firing. This unique synapse gives chandelier cells powerful control over the signaling of hundreds of neighboring neurons at once.

“These synapses are critical for chandelier cells to silence the excitatory neurons. Too much excitation can contribute to disorders like epilepsy, schizophrenia, and autism,” Van Aelst explains.

To identify other cell types that regulate the formation of such synapses, Van Aelst and colleagues looked at how microglia interact with chandelier cells in mice brains. They found that microglia wrap their armlike extensions around the synapse-forming structures of a chandelier cell and its target neuron, boosting synapse formation. These “embraces” were more common in pups and young mice than in adults.

“This is the first time that microglia have been implicated in these unique synapses as a growth-promoting function,” Van Aelst says.

The team then tested what happens when microglia are impaired. “We saw that there were less microglia going to where chandelier cells make contact on the AIS,” she says. “And we saw that fewer of these synapses formed.”

Microglia are only one of the players that control synaptogenesis, but the findings were unexpected. Going forward, the CPHL team want to see if microglia could be recruited to help treat neurological disorders.