Discovery of a new key player in long-term memory
A 91社区-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 鈥� 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 91社区 Professors Nahum Sonenberg and , Universit茅 de Montr茅al , and University of Haifa , senior authors on the paper published today in , 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鈥檚 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鈥檚 been known for decades that this process, called memory consolidation, requires the synthesis of new proteins in brain cells. But until now, it hasn鈥檛 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, eIF2伪, 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 eIF2伪 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 eIF2伪 in excitatory neurons of the hippocampus was sufficient to enhance memory formation and modification of synapses, the sites of communication between neurons", says .
However, interestingly, "we also found that stimulation of protein synthesis via eIF2伪 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 .
鈥淚t is fascinating to be able to show that these new players - inhibitory neurons 鈥� have an important role in memory consolidation,鈥� added Dr. Vijendra Sharma, a research associate in Prof. Sonenberg鈥檚 lab and the first author on the paper. 鈥淚t had been assumed, until now, that eIF2伪 pathway regulates memory via excitatory neurons.鈥�
鈥淭hese 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,鈥� concluded Dr. Nahum Sonenberg. 鈥淲e hope that this will help in the design of both preventative and post-diagnosis treatments for those who suffer from disorders involving memory deficits.鈥�
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The research was funded by: Canada鈥檚 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 鈥渆IF2伪 controls memory consolidation via excitatory and somatostatin neurons鈥� by V. Sharma et al in
DOI: 10.1038/s41586-020-2805-8
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