News Release 

Discovery of a new key player in long-term memory

Long-term memory controlled by protein synthesis in inhibitory cells

McGill University

Research News

A McGill-led multi-institutional research team has discovered that during memory consolidation, there are at least two distinct processes taking place in two different brain networks - the excitatory and inhibitory networks. The excitatory neurons are involved in creating a memory trace, and the inhibitory neurons block out background noise and allow long-term learning to take place.

The team, led by McGill University Professors Nahum Sonenberg and Arkady Khoutorsky, Université de Montréal Professor Jean-Claude Lacaille, and University of Haifa Professor Kobi Rosenblum, senior authors on the paper published today in Nature, also found that each neuronal system can be selectively manipulated to control long-term memory. The research, which answers a long-standing question about which neuronal subtypes are involved in memory consolidation, has potential implications for novel targets for medication for disorders such as Alzheimer's disease and autism, which involve altered memory processes.

Looking for the neurons involved in memory consolidation

How do short-term memories (which last just a few hours) transform into long-term memories (which may last years)? It's been known for decades that this process, called memory consolidation, requires the synthesis of new proteins in brain cells. But until now, it hasn't been known which subtypes of neurons were involved in the process.

To identify which neuronal networks are essential in memory consolidation, the researchers used transgenic mice to manipulate a particular molecular pathway, eIF2α, in specific types of neurons. This pathway had already been shown to play a key role in controlling the formation of long-term memories and regulating protein synthesis in neurons. Moreover, earlier research had identified eIF2α as pivotal for both neurodevelopmental and neurodegenerative diseases.

Excitatory and inhibitory systems both play a role in memory consolidation

"We found that stimulation of protein synthesis via eIF2α in excitatory neurons of the hippocampus was sufficient to enhance memory formation and modification of synapses, the sites of communication between neurons", says Dr. Kobi Rosenblum.

However, interestingly, "we also found that stimulation of protein synthesis via eIF2α in a specific class of inhibitory neurons, somatostatin interneurons, was also sufficient to augment long-term memory by tuning the plasticity of neuronal connections", says Dr. Jean-Claude Lacaille.

"It is fascinating to be able to show that these new players - inhibitory neurons - have an important role in memory consolidation," added Dr. Vijendra Sharma, a research associate in Prof. Sonenberg's lab and the first author on the paper. "It had been assumed, until now, that eIF2α pathway regulates memory via excitatory neurons."

"These new findings identify protein synthesis in inhibitory neurons, and specifically somatostatin cells, as a novel target for possible therapeutic interventions in disorders such as Alzheimer's disease and autism," concluded Dr. Nahum Sonenberg. "We hope that this will help in the design of both preventative and post-diagnosis treatments for those who suffer from disorders involving memory deficits."

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The research was funded by: Canada's International Development Research Centre (IDRC), in partnership with the Azrieli Foundation, the Canadian Institutes of Health Research (CIHR), and the Israel Science Foundation (ISF) to K.R. and N.S., JCL is supported by a CIHR Project grant and a Canada Research Chair in Cellular and Molecular Neurophysiology.

To read "eIF2α controls memory consolidation via excitatory and somatostatin neurons" by V. Sharma et al in Nature

DOI: 10.1038/s41586-020-2805-8

About McGill University

Founded in Montreal, Quebec, in 1821, McGill University is Canada's top ranked medical doctoral university. McGill is consistently ranked as one of the top universities, both nationally and internationally. It is a world-renowned institution of higher learning with research activities spanning two campuses, 11 faculties, 13 professional schools, 300 programs of study and over 40,000 students, including more than 10,200 graduate students. McGill attracts students from over 150 countries around the world, its 12,800 international students making up 31% of the student body. Over half of McGill students claim a first language other than English, including approximately 19% of our students who say French is their mother tongue.

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