2 brain networks team up for long-term memory

New research with mice shows 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 researchers 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.

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.

“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 co-senior author Kobi Rosenblum, a professor at the University of Haifa.

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 co-senior author Jean-Claude Lacaille of  Université de Montréal.

“It is fascinating to be able to show that these new players—inhibitory neurons—have an important role in memory consolidation,” adds first author Vijendra Sharma, a research associate in the lab of Nahum Sonenberg, a professor at McGill University. “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,” Sonenberg says.

“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 appears in Nature.

Funding for the research came from Canada’s International Development Research Centre, in partnership with the Azrieli Foundation; the Canadian Institutes of Health Research (CIHR); and the Israel Science Foundation.

Source: McGill University

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