Assembling a comprehensive map of all the connections between neurons of the brain is the task employed by neuroscientists currently working on the human connectome. The data from this effort should provide a blueprint that will allow scientists to relate brain function to anatomy. However, scientists from Carnegie Mellon University have recently observed a subset of neurons that may stymie their mapping efforts by “cloaking” synapses temporarily.

To use a sci-fi analogy, it would similar to a cloaking device from Star Trek that allows a ship to be concealed until it fires its weapons. The Carnegie Mellon team found that the inhibitory neurons, called somatostatin cells, emit a signal—analogous to a cloaking device—that quiets adjacent excitatory neurons. The synapse, much like a cloaked ship, cannot be seen unless it’s firing, so when the somatostatin cells are activated they cause the local network of neurons to be undetectable by researchers.       

The results from this research were published online recently in Current Biology through an article entitled “Neocortical Somatostatin Neurons Reversibly Silence Excitatory Transmission via GABAb Receptors”.

“It was totally unexpected that these cells would work this way,” said Alison Barth, Ph.D., professor of biological sciences at Carnegie Mellon University and senior author on the study. “Changing the activity of just this one cell type can let you change the brain's circuit structure at will. This could dramatically change how we look at—and use—the connectome.”

Dr. Barth’s team stumbled upon the synaptic cloaking pathway during some routine analysis that yielded results which weren’t quite in sync with previously reported data. The team assumed the synapse response would be strong, consistent, and grow in response to stimuli, but what they observed were weak and unreliable responses.

The investigators quickly realized that previous studies were conducted under ideal and optimized conditions for viewing synapses, where the Carnegie Mellon team was conducting experiments under conditions that reflect real-life conditions. These conditions reflect the noisy environment in which synapses normally reside.      

“There's this big black box in neuroscience. We know how to make synapses stronger in a dish. But what's going on in the brain to initiate synaptic strengthening in real life?” Dr. Barth asked.

In order to find the answer, Dr. Barth and her team observed pyramidal cells, a type of excitatory neuron, from the neocortex and found that many of the neurons were either not functioning or firing at an unexpectedly low level. Conversely, when the team recorded the activity of the somatostatin cells, they found the neurons to be much more active then they anticipated.

“The somatostatin cells were so active, I wondered if they could possibly be driving the inhibition of synapses,” stated Joanna Urban-Ciecko, Ph.D., postdoctoral fellow in Dr. Barth’s laboratory and lead author of the study.  

Dr. Urban-Ciecko was able to test her hypothesis by using a technique called optogenetics, which was able to control the activity of the neurons by using a precise wavelength of light. Specifically, the light activates an enzyme that was able to turn the somatostatin neuron on or off. The team found that when the cells were turned on, the synapse became weaker and in some cases disappeared completely—like being cloaked. They were also able to determine that the somatostatin neurons activated the GABAb receptors in the vicinity, which suppressed excitatory neurons and rendered them invisible.

“You have inputs coming at you all the time, why do you remember one thing and not the other?” “We think that somatostatin neurons may be gating whether synapses are used, and whether they can be changed during some important event, to enable learning,” concluded Dr. Barth.








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