Montreal researchers probe the genetic basis of memory

A group of Montreal researchers has discovered that GCN2, a protein in cells that inhibits the conversion of new information into long-term memory, may be a master regulator of the switch from short-term to long-term memory. Their paper Translational control of hippocampal synaptic plasticity and memory by the eIF2a kinase GCN2, which was published in the August 25th issue of the journal Nature, provides the first genetic evidence that protein synthesis is critical for the regulation of memory formation.

This new discovery is the fruit of an international collaboration. The work of McGill researchers Nahum Sonenberg, Karim Nader, Wayne Sossin and Claudio Cuello, Jean-Claude Lacaille and Nabil Seidah of the Université de Montréal, and David Ron of New York University sheds light on the mysterious workings of the hippocampus, a region of the brain responsible for learning and memory.

“Not all new information we acquire is stored as long-term memory,” says Dr. Costa-Mattioli, a post-doctoral fellow in the laboratory of Dr. Sonenberg, who spearheaded the research project. “For example, it takes most people a number of attempts to learn new things, such as memorizing a passage from a book. The first few times we may initially succeed in memorizing the passage, but the memory may not be stored completely in the brain and we will have to study the passage again.”

In a series of experiments, the researchers demonstrated that mice bred without the GCN2 protein (known as transgenic mice) acquire new information that does not fade as easily as that of normal mice. This new information is more frequently converted into long-term memory. The researchers concluded that GCN2 may prevent new information from being stored in long-term memory.

Adds Dr.Jean-Claude Lacaille: “The process of switching to long-term memory in the brain requires both the activation of molecules that facilitate memory storage, and the silencing of proteins such as GCN2 that inhibit memory storage.”

Although research on humans is still a distant possibility, the scientists believe their discovery may hold promise in the treatment of a variety of illnesses linked to memory. “The discovery of the role of GCN2 in long-term memory may help us develop targeted drugs designed to enhance memory in patients with memory loss due to illnesses such as Alzheimer’s disease, where protein synthesis and memory are impaired,” concludes Dr. Karim Nader.