A previously unknown type of synapse appears to be hidden in the strange hair-like appendages found on the surface of neurons, a new study reveals.
Studies in mice suggest that structures called primary cilia play a role in neuronal signaling. Specifically, it serves as a shortcut to transmit signals directly to the nucleus that trigger changes to chromatin, the complex that makes up chromosomes.
The discovery not only helps scientists unravel the role of these mysterious structures in other cells, but may also help us better understand the complex workings of the brain.
“This particular synapse represents a way to change what is being transcribed or made in the nucleus, changing the whole program,” said Howard Hughes Medical Institute’s Janelia Research Campus, M.D. says David Clapham.
“It’s like a new dock on the cell that allows rapid access to chromatin changes. This is very important because chromatin changes so many aspects of the cell.”
Primary cilia are found protruding from the surface of almost all mammalian cells. Some of them have well-understood roles, such as helping move mucus around in the lungs, but in many cells their function is poorly understood.
In some cases, they also act as antennas to receive signals from external stimuli. For example, in photoreceptor cells, they are responsible for processing light.
Primary cilia are thought to be vestiges of our unicellular origin billions of years ago, but what function they play in neurons remains a mystery.
That’s at least in part because they’re so small that they’re difficult to spot with traditional imaging techniques, researchers say.
But recent advances have made it easier to see smaller, finer structures, prompting a team led by neuroscientist Shu-Hsien Sheu of Janelia’s Clapham Lab to take a closer look.
The researchers performed studies in both live adult mice and fixed brain specimens. Using focused ion beam scanning electron microscopy to study neurons at high resolution, they found that cilia can form synapses (structures that allow neurons to exchange signals between cells) in the axons of neurons. Did.
In the second phase of the study, researchers will use a newly developed biosensor in conjunction with a technique called fluorescence lifetime imaging (FLIM) to monitor biochemical changes taking place within the cilia of living mice. Observed the process.
This allowed the team to step-by-step analyze the process by which the neurotransmitter serotonin is released from axons to receptors on cilia. From there, a cascade of signals opens the chromatin in the neuron’s nucleus, altering the genetic material within.
The team refers to their findings as ‘axon-ciliary synapses’ or ‘axon-ciliary’ synapses, which implement longer-lasting changes than axon-dendrites because the signals cause changes in the cell nucleus. states that it may be involved in synaptic connections.
Therefore, the ciliary body synapse may be a shortcut to long-term genomic alterations.
The next step in research is to probe other receptors on the primary cilia of neurons. Although this study focused solely on serotonin, the researchers say there are at least seven neurotransmitter receptors that need further investigation.
Following a better understanding of neuronal cilia, the team hopes to investigate the role of primary cilia in other organs. A more detailed understanding of how the body works is always good.
Of course, we first need to make sure that the ciliary synapse exists and functions in the same way in the human brain.
“Everything we learn about biology may help people live better lives,” says Clapham. “If you can understand how biology works, you can solve problems.”
This research cell.