MAR 11, 2015

Roadblock in Mapping the Human Connectome

WRITTEN BY: Brenda Kelley Kim
The human connectome can be described as a map of the millions of connections between all of the neurons in the brain. Much like understanding the human genome, a map of genes that regulate the body, neuroscientists hope to be able to create a blueprint of the connectome. With this information, it is believed that researchers can link brain anatomy and structure to brain function.

There's a roadblock to this journey however, with recent research from Carnegie Mellon University. A team from the university's BrainHub has discovered a specific type of neuron that could be preventing scientists from seeing the whole picture. This neuron appears to be temporarily cloaking synapses in the brain that connect a large group of neurons. Like a tree or large billboard that hides a highway patrol officer trying to catch speeders, this neuron is essentially blocking the view of the synaptic reactions between neurons by silencing their activity.

Synaptic activity in the brain cannot be detected unless a group of neurons is actively firing off electrical charges. In the study published in the March 16 issue of Current Biology, the researchers found that a class of inhibitory neurons, called somatostatin cells, send out a signal hat silences neighboring excitatory neurons. With this activity silenced, the local network of neurons is invisible to researchers.

The Carnegie Mellon researchers discovered this synaptic cloaking device in a very ordinary way considering it's potentially extraordinary significance. They were conducting their normal research and noticed that something just didn't look quite right.

Joanna Urban-Ciecko, a research scientist in Barth's lab, noticed that the synapses in her experiments were behaving differently than previous researchers had reported. Up until then, research showed strong reliable synapses that grew in response to stimulus, but the neurons in her work were weak and did not grow.
Urban-Ciecko's research was was being done under real-life conditions, whereas prior research was done under specifically created conditions. The problem is those conditions do not reflect the actual brain environment.

To find out what was going on in real time in the brain, as opposed to lab created conditions, Urban-Ciecko looked at neurons in the brain's neocortex that were functioning under normal, noisy conditions. She took paired-cell recordings from pyramidal cells, a type of excitatory neuron, and found that many of the synapses between the neurons were not functioning, or functioning at an unexpectedly low level. Urban-Ciecko then recorded the activity of somatostatin cells, a type of inhibitory neuron, and found that those neurons were much more active than expected.

"The somatostatin cells were so active, I wondered if they could possibly be driving the inhibition of synapses," Urban-Ciecko said.
To test her hypothesis, Urban-Ciecko turned to optogenetics, a technique that controls neurons with light. The light activated an enzyme that controls the somatostatin neurons. When these neurons were activated, the excitatory neurons slowed down. When they were silenced, the activity of the pyramidal cells went up. They were able to observe that the somatostatin neurons activated GABAb receptors which then suppressed the action of the excitatory neurons.

The researchers next plan to see if the somatostatin cells behave similarly in other areas of the brain. If they do, it could represent a novel target for studying and improving learning and memory.