A new drug target for anxiety disorders — and particularly post-traumatic stress disorder (PTSD) — is now possible due to a recent unexpected discovery by UCLA scientists. Their research has honed in on neuronal gap junctions — channels in which electrical communication occurs between inhibitory neurons.
The discovery also holds promise for Alzheimer’s disease and other memory-related disorders.
“The brain has many processes we have not yet explored,” said UCLA Professor of Psychology Dr. Michael Fanselow. “Understanding them and how they normally work can open up new approaches that may help in very prevalent and debilitating diseases, such as anxiety disorders and memory disorders.”
Gap junctions form where inhibitory neurons touch one another. They are an opening between nerve cells that allow electrical activity to pass from one neuron to another.
When an individual has a terrifying experience, there is often a lingering fear of the place where it happened. This occurs because the nerve cells in certain brain regions increase their ability to excite or stimulate one another, said Fanselow, leader of the study and member of UCLA’s Brain Research Institute.
So far, most studies have emphasized that this experience happens because of the communication among neurotransmitters moving across synapses (spaces between neurons). However, there is also direct electrical contact among other small, inhibitory neurons in these areas as well, and these connect through gap junctions, Fanselow said.
“I was completely surprised by this discovery,” he added. “I really thought we were taking a long shot and was surprised that gap junctions were not only playing a role but that their importance was so great.”
Interestingly, these gap junctions are very common in invertebrates but rare in mammals, where they can only be found on certain inhibitory interneurons.
“Because of this, no one has looked at the importance of these gap junctions for learning, memory and emotion,” Fanselow said. “We hypothesized that these gap junctions may be very important. Because the gap junctions cause the inhibitory neurons to fire together, they may cause these inhibitory neurons to act as a pacemaker for the excitatory neurons, making them fire at the same time so they are better able to make fear memories.”
The study included the use of several drugs that block gap junctions in rats, and it was discovered that because the medications disrupted vital rhythms in the dorsal hippocampus (a brain region most associated with cognition), they were able to keep any “fear of place” memories from forming.
The drug injections worked when given right after a frightening experience, revealing that they could be particularly useful for PTSD. Also, the drugs were just as effective when regularly injected into a cavity near the abdomen as when put directly into the brain.
“Because we don’t know when a person will experience trauma, treatments that can work after the experience hold more promise,” Fanselow said.
“Our research shows a way that neurons can coordinate their activity, and this coordination is critical for memory formation,” Fanselow said. “Perhaps if we had a way of enhancing gap junction function, we may improve memory formation by facilitating gap junctions when memory is impaired by diseases such as Alzheimer’s. However, we have not shown this yet.”
Fanselow noted that the formation of fear memories is what drives anxiety disorders, which are quite common and can be very debilitating. “Gap junctions appear to be key in coordinating the activity of the network of neurons that produce fear memories, specifically, and probably other memories, generally, as well,” he said.
Source: University of California