Michael S. Fanselow, Ph.D., a 2011 NARSAD Distinguished Investigator Grantee and professor of psychology at the University of California at Los Angeles, points out that we experience fear, just as we experience pain, for important reasons – reasons that relate to our ability to survive as individuals and, by extension, as a species. A single failure on our part to engage in other primal activities – eating a single meal or mating on a single occasion – won’t kill us. But failing even one time to respond very rapidly to an oncoming car or a knife-wielding attacker could indeed prove fatal.

The quest of Dr. Fanselow’s laboratory at UCLA is to understand how fear is encoded and communicated within the human brain. His team focuses on understanding PTSD and other anxiety disorders in which fear memories cannot properly be extinguished in patients, such as combat veterans or victims of physical or psychological trauma, and they come to dominate or interfere with normal life. He and his team focus their study on brain areas such as the amygdala and hippocampus that are well known to play a vital role in the processing of emotions and in learning and remembering.

Fanselow is particularly interested in understanding how the context in which a fear is experienced is processed. His work has led him to challenge a long-held view that fear circuitry is “hard-wired,” the product of processing by what might be called dedicated circuits, constructed to handle specific classes of learning and memory problems. He is exploring, in contrast, how the underlying biology and electrochemistry responds dynamically to fearful or anxiety-producing experience.

The team published a fascinating study recently in the journal Science related to this issue. They trained rats in classic Pavlovian fashion, teaching them to associate the sound of a tone with the experience of receiving a small foot shock. This leads the animals to respond fearfully whenever they hear the tone regardless of where they hear it. The rats also show fear if they are returned to the context or place associated with the uncomfortable experience. This is called “fear learning.”

After fear learning, Dr. Fanselow’s team gave the rats exposure therapy (also called extinction), where experiencing the tone cue without an aversive experience teaches the rat that the tone is not dangerous any more. This is very effective at reducing fear to the cue, says Dr. Fanselow. “Unfortunately, this learning does not generalize to other contexts,” he notes. The animals have learned two opposing memories: in one, they learned to be fearful when they heard the tone; later they learned not to be afraid when they heard it. These compete with one another, but the newer one does not obliterate the other. They coexist. The aim of the study was to test whether certain drugs might render fear memories susceptible to interruption independently of the context in they were learned.

The drugs in question block the transmission of electrical signals between tiny gaps between adjacent nerve cells in the brain. These so-called gap-junctions are analogous to chemical synapses, the small spaces between nerve cells across which signals are transmitted at the prompting of chemical neurotransmitters such as glutamate, dopamine, and GABA. Gap junctions, across which electrical signals travel, are even tinier – as much as 10 times smaller than chemical synapses.

Dr. Fanselow’s team showed that electrical synapses, like chemical ones, are involved in the mechanisms underlying fear learning and memory. And they made an exciting discovery: by blocking electrical gap junctions, they were able to disrupt the contextual encoding of fear-inducing experiences. A consequence was that now, the “safe” memory – in which the sound of the tone is not associated with a fearful experience – was recalled by the rats, regardless of the context in which it was presented. “In other words,” says Dr. Fanselow, the therapeutic result was "now able to take over, or generalize, outside of the therapy context.” The finding leads Dr. Fanselow to propose that a new class of therapeutics might be designed that block gap junctions before or during the period in which an adverse experience is “consolidated” in memory – detaching it, in effect, from its context, in order to more effectively treat trauma and anxiety disorders.