It was surprising to the researchers that no one had studied these cells before given the references to them in important scientific papers going back for over a hundred years.
"This is a well-studied part of the brain," said Ben W. Strowbridge, Ph.D., associate professor of neuroscience at Case and the senior author. "These are large cells that weren't really hiding."
The perception of a smell begins when odor molecules in the air interact with one of the millions of specialized olfactory sensory neurons in the nose. These sensory neurons then send signals to a brain region called the olfactory bulb, where the work of recognizing the odor begins. One of the puzzling aspects of olfaction is how our perception of an odor can evolve over multiple sniffs. Because of their unique ability to maintain their activity between sniffs, Blanes cells may provide the missing link needed to answer this critical question. While there are relatively few Blanes cells in the brain, they appear to play a critical role in shaping the output of the olfactory system.
The Case researchers found that the influence of Blanes cells on the output signals leaving the olfactory bulb is magnified hundreds of times by the specific pattern of connections they make with other cell types. One of the surprising results from their study was the discovery that Bla nes cells selectively choose to talk with another cell type in the olfactory bulb, the granule cell. It is this specific pattern of connections that explains how Blanes cells can have such a disproportionately large impact in the olfactory system.
Discovering how one brain cell talks with another brain cell remains one of the most important but technically challenging questions in neuroscience. The Case researchers faced two significant hurdles in trying to answer this question in the olfactory system. The first was the shear numbers of potential partner neurons each Blanes cell might have. The other hurdle relates to difficulty in visualizing the incredibly thin connection between the Blanes cell and its target neurons.
Todd Pressler, a doctoral candidate student in Strowbridge's lab and the lead author on the study, took advantage of a new type of imaging method called multiphoton microscopy to overcome these hurdles and to discover that Blanes cells talk to granule cells.
"The multiphoton microscope allowed me to identify the axon and then follow it for long distances without damaging the Blanes cell. Once I could follow the axon as it coursed through the brain, it was relatively easy to see where it ended and where I should look for potential target cells. Because I knew where to look, this part of the project was shortened from potentially years to just a matter of weeks", said Pressler.
The multiphoton microscope used in this study was built by Strowbridge specifically for these types of experiments and was funded by grants from the Mt. Sinai Health Care Foundation and the National Institutes of Health.
Strowbridge and Pressler highlighted two distinct set of experiments they hope to pursue in the near future. The first relates to the possible connection between the sense of smell and Alzheimer's disease. The Case investigators found that the same biological machinery that helps the olfactory brain to remem ber smells is identical to the machinery that enables other types of memories in the cortical brain region most susceptible to damage in this debilitating disease.
"By understanding the biological process that allow us to store memories in the olfactory brain, we might find a novel window into pathological changes that affect memory in people with Alzheimer's disease," said Strowbridge.
In addition to leveraging the olfactory system to better understand Alzheimer's disease, Pressler is excited about the prospect of unraveling the patterns of synaptic connections made by the other five named but as yet unstudied brain cells in the olfactory bulb.