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."
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.
Reference:
Vijendra Sharma, Rapita Sood, Abdessattar Khlaifia, Mohammad Javad
Eslamizade, Tzu-Yu Hung, Danning Lou, Azam Asgarihafshejani, Maya Lalzar,
Stephen J. Kiniry, Matthew P. Stokes, Noah Cohen, Alissa J. Nelson,
Kathryn Abell, Anthony P. Possemato, Shunit Gal-Ben-Ari, Vinh T. Truong,
Peng Wang, Adonis Yiannakas, Fatemeh Saffarzadeh, A. Claudio Cuello, Karim
Nader, Randal J. Kaufman, Mauro Costa-Mattioli, Pavel V. Baranov, Albert
Quintana, Elisenda Sanz, Arkady Khoutorsky, Jean-Claude Lacaille, Kobi
Rosenblum, Nahum Sonenberg. eIF2α controls memory consolidation via
excitatory and somatostatin neurons. Nature, 2020; DOI:
10.1038/s41586-020-2805-8