The Biology Of Induced Memory

Two years after the publication of "Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval" in the August 14, 2000 issue of Nature, Dr. Nader and his colleague from New York University , neuroscientist Joseph E. Ledoux, published in the October 24, 2002, issue of Neuron, an article which shows that the same reconsolidation process goes on in another part of the brain which mediates conscious memories, the hippocampus.

"Whether we speak of rats or human beings, we store memories in analogous areas of the brain," say Dr. Nader, now a professor in the McGill Department of Psychology. " Our first findings were based on earlier work identifying the amygdala as a site at which neural changes that underlies auditory fear learning occur. It is a kind of learning that can happen unconsciously. We found evidence that contradicts entrenched psychological and neurobiological models of memory. Current theories posit that memories are processed by our brain initially as sensitive, labile short-term memories (stm) and then get stored as long-term memories (ltm). the transition from stm to ltm is mediated by the production of proteins. Once stored, the memory trace is posited to be "fixed" or "consolidated" in the brain. We found that stored fear experiences in the amygdala, when retrieved, return to a state that again requires protein synthesis in order to be restored or reconsolidated. Thus, if you reactivate the fear memory and block the production of protein in the amygdala immediately afterwards, the memory is lost."

In the Neuron article, Dr. Nader and his colleague from New York University extended this work to the part of the memory system that contributes to mediating conscious or declarative memories, called the hippocampus. They conditioned rats to fear the environment in which they were (i.e. a small box) by inducing a light electric shock on their paws.

This paradigm engaged the hippocampus to process information about the context that can be used to predict shock. The hippocampal contributions to this paradigm are thought to engage similar processes as declarative memories in humans. "According to the cellular theory of memory, new memories require new protein synthesis to be stored," explains Dr Nader.

"The hippocampus also has a second level of consolidation called systems consolidation theory. This posits that the hippocampus has a time-limited role in memory storage, after which the memory is independent of the hippocampus. This is why amnesiacs such as H.M. (the patient of neuropsychologist Brenda Milner) who have damage to their hippocampus can remember events that happened a few years ago but can't remember recent events."

Before testing cellular reconsolidation in the hippocampus, professors Nader and Ledoux showed that intra-hippocampal infusions of the protein synthesis inhibitor anisomycin caused amnesia for a consolidated hippocampal-dependant contextual fear memory, but only if the memory was reactivated prior to infusion. "This demonstrated that memories stored in the hippocampus can undergo cellular reconsolidation or restorage," said Dr. Nader. "Surprisingly, the effect occurred even if reactivation was delayed for 45 days after training, a time when declarative memory is independent of the hippocampus. In fact, we found that if you lesion the hippocampus 45 days after conditioning, there is no effect. Therefore the memory of the context has to be independent of the hippocampus. However, if the memory is now reactivated immediately prior to lesions, there is a large effect. Thus, mature old memories stored in our cortex return to being dependent on the hippocampus after they are reactivated, an instance of systems reconsolidation."

This time Dr. Nader's findings may also explain why the memory we have of an accident scene, for example, can be tampered without our knowledge. In this instance, you witness a car crash and you hear someone saying "Oh! see what happened to the poor guy in the red jacket" . You will remember the red jacket although there was no one on the accident scene wearing the garment. This is called false memory syndrome. Dr.nader has now shown the biological basis for it.

Karim Nader received his Ph.D. from the University of Toronto under the supervision of Derek van der Kooy. After completing his Ph.D., which was aimed at elucidating how many motivational systems there are in the brain, he moved to New York University to commence post-doctorate work with Joseph E LeDoux. In the last few years, he has published work addressing the neural organization of fear system at neurochemical, and molecular levels of analysis. A Research Assistant Professor at the Center for Neural Science, NYU, he joined the McGill University Department of Psychology in 2001. This research was supported by grants from the International Human Frontiers of Science program and the Volkswagen Foundation.