A previously unknown type of synapse appears to be hidden in strange hair-like appendages that can be found on the surface of neurons, new research shows.
A study in mice shows that structures called primary cilia play a role in neuronal signaling. Specifically, they act as a shortcut for delivering signals directly to the nucleus to trigger changes in chromatin, the complex that forms chromosomes.
The discovery may help scientists unravel the role of these mysterious structures in other cells and give us a deeper understanding of the complex workings of the brain.
“This particular synapse represents a way to alter transcription or manufacturing in the nucleus, which changes the entire program,” said David Clapham, MD, of the Howard Hughes Medical Institute’s Janelia Research Campus.
“It’s like a new dock on the cell, giving quick access to chromatin changes, which is very important because chromatin changes so many aspects of the cell.”
Primary ciliary protrusions can be found on the surface of nearly all mammalian cells—some with well-known roles, such as those that help move around mucus in our lungs—but in many cells, their function is poorly understood.
In some cases, they can act as antennae for receiving external stimulation signals. In photoreceptor cells, for example, they play a role in processing light.
Primary cilia are thought to be relics of our single-cell origins billions of years ago, but their role in neurons has long been a mystery.
That’s at least in part because they’re so small that they’re hard to spot with traditional imaging techniques, the researchers said.
However, recent advances have made it easier to see smaller, finer structures, prompting a careful study by a team led by neuroscientist Shu-Hsien Sheu in Janelia Clapham’s lab.
The researchers studied live adult mice and fixed brain samples. Using focused ion beam scanning electron microscopy to study neurons at high resolution, they determined that cilia can form synapses with neuronal axons—a structure that allows neurons to exchange signals between cells.
In the second phase of the study, the researchers used a newly developed biosensor combined with a technique called fluorescence lifetime imaging (FLIM) to observe the biochemical processes taking place inside the cilia of living mice.
This allowed the team to gradually break down the release of the neurotransmitter serotonin from axons to receptors in cilia. From there, a series of signals open up the chromatin in the neuron’s nucleus, thereby changing the genetic material inside.
The team dubbed their findings “axon-ciliary synapses” or “axon-cilia” synapses, and said that since these signals trigger changes in the nucleus, they may be responsible for achieving longer-term than axon-dendritic changes in synaptic connections.
Thus, ciliary synapses may be a shortcut to long-term genomic changes.
The next step in the research will be to take a closer look at other receptors on the primary cilia of neurons. The study focused only on serotonin, but there are at least seven other neurotransmitter receptors that need further study, the researchers said.
With a better understanding of neuronal cilia, the team hopes to study the role of primary cilia on other organs. It’s always good to know more about how the body works. For example, it could lead to the development of more targeted and specialized treatments.
Of course, it first needs to be determined whether ciliary synapses exist and work the same way in the human brain.
“Everything we learn about biology may help people lead better lives,” Clapham said. “If you can figure out how biology works, you can solve problems.”
The research has been published in cell.