An international team of researchers from different institutions has just announced in the journal Cell the discovery of a type of synapse unknown until now, as it remained hidden in the strange hair-like appendages that can be seen on the surface of the neurons.
In their study, carried out on mice, the researchers explain that these appendages, called primary cilia, play a role in neuronal signaling that had gone unnoticed. Specifically, they act as a ‘shortcut’ to transmit signals directly to the neuronal nucleus and trigger changes in chromatin, the complex that forms chromosomes.
The finding will help scientists to understand much better how the brain works, but also to unravel the role that these mysterious structures play in other types of cells.
“This special synapse,” explains David Clapham, of the Janelia Research Campus of the Howard Hughes Medical Institute and a co-author of the study – represents a way to change what is transcribed or done in the core, and that can change entire programs. It’s like a new cell spring that gives quick access to chromatin changes, and that’s very important because chromatin changes so many aspects of the cell.”
The mystery of the cilia
Los primary cilia they protrude from the surface of almost all mammalian cells. Some of them have well-understood functions, such as helping to move mucus in our lungs, but in many other cases the role they play is not known. Sometimes these cilia act as antennae that receive signals from external stimuli, as in the case of photoreceptor cells, where they play a role in processing light. But on many other occasions it is completely unknown what its mission could be.
Primary cilia are thought to be a holdover from our single-celled origins billions of years ago, but their role in neurons has been a mystery until now. In fact, according to the researchers, they are so small that they are difficult to distinguish with traditional imaging techniques.
However, recent advances in microscopy have made it possible to see ever smaller and finer structures, leading a team led by neuroscientist Shu-Hsien Sheu from Janelia’s Clapham Laboratory, to take a much closer look.
To study the neurons in high resolution, the team used ion-beam scanning electron microscopy to determine that cilia can form a synapse, a structure that allows neurons to exchange signals with each other, through the axons.
In a second stage of the research, Sheu and colleagues used a newly developed biosensor along with a technique called Fluorescence Lifetime Imaging (FLIM), to observe the biochemical processes taking place inside cilia in living mice. In this way, they managed to break down, step by step, the process by which the neurotransmitter serotonin is released from the axon to the receptors on the cilia. From there, a cascade of signals opens up the chromatin in the nucleus of the neuron, allowing changes to the genetic material inside.
The study authors call their discovery a ‘axo-ciliary synapses‘ or ‘axon-cilia’, and argue that, because the signals trigger changes directly in the cell nucleus, they could be responsible for implementing longer-term changes than the classic axon-dendrite synaptic connection. The ciliary synapse could therefore be a shortcut for long-term genomic changes.
The next step in the research will be to take a closer look at other receptors on primary neuronal cilia. The current study only focused on serotonin, but there are at least seven other neurotransmitter receptors that warrant further investigation.
Furthermore, Sheu and colleagues would like to investigate the role of primary cilia in other organs, which will provide a better and more detailed understanding of how the human body works and lead, for example, to the development of more targeted and effective drugs.