New Type of Neuron Discovered as Playing Key Role in Long-Term Memory Formation

Mary-Margaret Cummings ‘24, Neuroscience, Fall 2020

Figure: Neurons (Source: ShutterStock)

While you remember what you had for lunch today, you probably won’t remember that in a week. However, you might still be able to recall your favorite teacher from grade school. Here, two kinds of memory are being illustrated—long-term memory (LTM), which lasts for years, and short-term memory (STM), which lasts from a few seconds to several hours at the most.³ Transient memories exist for a short time because they only rely on modifications to existing proteins in neurons. In contrast, long-term memories are characterized by new neural connections being formed; they have an extended physical presence in the brain, and their strength depends on how often they are activated.¹

The question remains: What has to happen for mere transient memories to transform into enduring recollections? The process, termed memory consolidation, requires new protein synthesis within brain cells to take place. For a long time, scientists were convinced some kind of “molecular switch” was responsible.³ Researchers even knew that the regulatory protein eIF2ɑ—Eukaryotic Initiation Factor 2ɑ—plays a pivotal role in both protein synthesis and LTM formation.^3,4 It was further assumed that memory consolidation occurred in excitatory neurons, a specific class of neurons.³

Now, an exciting new study—published in October of 2020 by a multi-institutional team led by researchers at McGill University—definitively revealed the two specific neuronal subtypes in which the eIF2ɑ protein facilitates memory consolidation.

The two classes are excitatory and inhibitory neurons.³ Excitatory neurons release neurotransmitters that depolarize postsynaptic neurons. Therefore, the postsynaptic neurons’ action potentials creep closer to the threshold potential required for them to fire. These postsynaptic neurons are “excited”; in other words, they can fire more easily. Inhibitory neurons do the opposite. They release neurotransmitters that hyperpolarize postsynaptic neurons. These postsynaptic neurons’ axons are more negatively charged, making them harder to activate.² The type of inhibitory neuron identified by the researchers as affecting LTM formation is called the somatostatin neuron.³

This study was performed on transgenic mice whose genomes were altered at the eIF2ɑ gene in a way that promoted heightened protein synthesis. In the group where the eIF2ɑ gene was altered in the excitatory neurons of the hippocampus, the enhanced protein synthesis stimulated memory formation and synapse modification. This was not altogether unexpected because excitatory neurons were already believed to have a role in memory formation. The unexpected finding was that the transgenic mice with altered elf2a expression in the somatostatin neurons exhibited enhanced synaptic plasticity, strengthening long-term memories.³

Most exciting are the research’s implications for treatments of disorders involving altered memory processes. Dr. Nahum Sonenberg of McGill University notes that the new clarification on somatostatin inhibitory neurons’ role in LTM formation presents a “novel target for possible therapeutic interventions in disorders such as Alzheimer’s disease and autism.” ³

References

1. Burnett , D. (2015, September 16). What happens in your brain when you make a memory? Retrieved October 19, 2020 from https://www.theguardian.com/education/2015/sep/16/what-happens-in-your-brain-when-you-make-a-memory.
2. Ibrahim , L. A. (2017, March 6). Inhibitory Neurons: Keeping the Brain’s Traffic in Check. Knowing Neurons. https://knowingneurons.com/2014/11/05/inhibitory-neurons-keeping-the-brains-traffic-in-check/.
3. McGill University. (2020, October 7). New key player in long-term memory: Long-term memory controlled by protein synthesis in inhibitory cells. ScienceDaily. Retrieved October 19, 2020 from www.sciencedaily.com/releases/2020/10/201007123121.htm

4. Costa-Mattioli, M., Gobert, D., Stern, E., Gamache, K., Colina, R., Cuello, C., … Sonenberg, N. (2007, April 6). eIF2alpha phosphorylation bidirectionally regulates the switch from short- to long-term synaptic plasticity and memory. Cell, 129(1), 195-206. Retrieved October 19, 2020 from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149214/.