Scientists from the Janelia Campus at Howard Hughes Medical Institute have made a surprising discovery, and it might help explain how brain cells communicate long-term changes to each other. Their findings, reported in the journal Cell, describe a new synapse between axons and primary cilia – hair-like structures present on different cell types including neurons.
Synapses normally span between the axon of one neuron and the dendrite of another, however, the new findings suggest that axons could take an alternative, shorter route and connect to special junctions of primary cilia to rapidly signal information to the cell’s nucleus, forming a new kind of synapse not seen before.
“This special synapse represents a way to change what is being transcribed or made in the nucleus, and that changes whole programs,” Janelia Senior Group Leader David Clapham, whose team led the new research, said in a statement.
The researchers used high-resolution microscopy, biosensors, and biochemical tools to peer deep into the cellular structures present in neuronal cells, observe the new synapse, and understand the downstream influence of the new signaling pathway. Specifically, they focused on axons that release the neurotransmitter serotonin.
The researchers were able to show, step by step, how a neuronal cell's axon releases serotonin onto the primary cilia of another neuronal cell, forming a new synapse. They were also able to gain a better understanding of the biochemical changes that occur downstream of this specific signaling mechanism.
Because primary cilia structures span from the interior of cells, close to the nucleus, all the way to the exterior of the cell's surface, signals passed across the ciliary synapse can enable changes to genomic material in the nucleus of these cells. The researchers, therefore, suggest that this signaling mechanism is more likely to transmit long-term changes anywhere in the cells in a faster, more selective manner.
The effects in the cell are not just short-term, Clapham explained – some can be long-term. “It is like a new dock on a cell that gives express access to chromatin changes, and that is very important because chromatin changes so many aspects of the cell.”
The signaling of the new synapse specifically targets chromatin – the mixture of DNA and proteins that forms chromosomes – inside the nucleus of cells. The researchers say the changes induced could therefore last anywhere from hours up to years, as they impact the genetic information of the cells. This does, however, open up the possibility that the new synapse could inform the creation of more targeted medication in the future, which is an exciting prospect.
“Everything we learn about biology may be useful for people to lead better lives, if you can figure out how biology works, you can fix things,” Clapham concluded.