Brunet is one of the few people studying reconsolidation in humans. In his trials, he administers a medicine called propranolol, which is already used to treat high blood pressure. It decreases blood pressure by blocking the action of epinephrine, a stress hormone, in the peripheral nervous system. But it also blocks the hormone in the amygdala, a part of the brain that plays a crucial role in storing the emotional components of memory. If Brunet proves that this treatment can weaken the grip of painful memories, he won’t just have found an alternative to behavioral therapy and existing drug treatments for PTSD, none of which work for everyone. He will also have demonstrated that it might be possible, through drug treatment, to fundamentally and precisely alter memories beyond the confines of the lab. The implications are immense. Brunet’s general approach to understanding memory could be used to treat a variety of anxiety disorders and addictions.
A Window of Vulnerability
At the simplest level, a memory is thought to be stored in the brain by a specific, well-connected circuit of nerve cells linked by junctions called synapses. New memories are formed when synapses form or existing synapses grow stronger as the brain processes events.
One of the tenets of modern neuroscience is that it takes time for these memories to become permanent–a process dubbed consolidation. In the 1960s, scientists subjected rats to various treatments that block normal brain signaling (for example, electroconvulsive treatment, or ECS, disrupts electrical signals by inducing seizures). The results showed that very new memories could easily be kept out of permanent storage. But if the disruptive treatments were administered a day or so after the new memory was created, they had no effect. Once a particular memory becomes resistant to interference, it is regarded as consolidated.
The first hint that long-term memories could be made malleable came in the 1960s too, just as the idea of consolidation was gaining ground. Through experiments similar to those that defined the time window for consolidation, scientists discovered that ECS could disrupt even an old memory in animals, if the animal was reminded of it first. To start, the researchers would condition rats to fear a particular sound by giving them a mildly painful shock every time they heard it. The animals would eventually freeze in fright on hearing the sound: the painful memory had been consolidated. But when the rats were given ECS treatment just after the memory was triggered by playing the sound, the fearful link between the sound and the shock was lost forever. Because this rather confusing finding conflicted with the dominant theory that consolidated memories are permanent, it was pursued only briefly, and then largely forgotten for the next 25 years.
Over the next few decades, scientists came up with more precise ways to study the molecular underpinnings of memory and consolidation. In 1999, for example, researchers in neuroscientist Joseph LeDoux’s lab at New York University found that injecting a drug that blocks protein synthesis directly into part of the brain disrupted consolidation of new memories. Researchers proposed that when the right proteins aren’t produced, nerve cells can’t make the connections that underlie memory formation at a cellular level.
In 2000, Karim Nader, then a postdoctoral researcher in LeDoux’s lab (he is now an associate professor at McGill), published a paper showing evidence that the same drug treatment could also erase long-term memories that had recently been recalled–a major new challenge to the prevailing views about consolidation. Nader, who was new to memory research but had access to neuroscience not available in the 1960s, outlined a specific theory explaining this observation. He proposed that recalling a memory actually causes the synapses encoding that memory to weaken or even to come apart. The molecular structure of the memory–the series of synapses in which it’s stored–is then re-formed, or reconsolidated, to make it stable once again.