黑料吃瓜资源

Microglia, the immune cells of the brain, are known for eating up unwanted items like germs and debris, much as their counterparts do in the rest of the body. In early childhood, certain microglia remove unneeded connections, or synapses, to shape the adult brain鈥檚 organized circuitry. Now, 黑料吃瓜资源 (CSHL) Professor Linda Van Aelst has found that in mice, microglia also help neurons grow synapses critical to cognitive functioning.

鈥淢ost immune cells are known to target and eat鈥攍et’s call it garbage,鈥� says Van Aelst. 鈥淏ut 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.鈥�

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

鈥淭丑别蝉别 synapses are critical for chandelier cells to silence the excitatory neurons. Too much excitation can contribute to disorders like epilepsy, schizophrenia, and autism,鈥� Van Aelst explains. She wondered what other cell types regulate the formation of such synapses.

Together with graduate students Nicholas Gallo and research assistant Artan Berisha, Van Aelst studied how microglia interact with chandelier cells. They found that microglia wrap their armlike processes around the synapse-forming structures of a chandelier cell and its target neuron, increasing proper synapse formation. These special embraces were more common in pups and young mice than in adults.

鈥淎nd that was really cool,鈥� she says. 鈥淭his is the first time that microglia have been implicated in these unique synapses as a growth-promoting function.鈥�

The team then tested what happens when microglia are impaired. 鈥淲e saw that there were less microglia going to where chandelier cells make contact on the AIS,鈥� Van Aelst says. 鈥淎nd we saw that fewer of these synapses formed.鈥�

Microglia 鈥渁re only one of the players that control synaptogenesis, but key players that people didn’t think of or expect,鈥� she says. Ultimately, the researchers want to see if microglia could be recruited to help treat neurological disorders.

Written by: Joyce Gramza, Science Writer | [email protected] | 516-367-8455

Funding

National Institutes of Health, National Institutes of Health Fellowship

Citation

Gallo, N.B., et al., 鈥淢icroglia Regulate Chandelier Cell Axo-axonic Synaptogenesis鈥�, PNAS, March 7, 2022. DOI: