While I was growing up, I remember my parents and teachers saying, “Your brain is like a sponge.” Of course, I didn’t understand what they meant, but as cliché as this statement is, it actually reveals a lot about children’s amazing abilities to absorb and remember impressive amounts of information. From new words and concepts, to detailed locations and even foul phrases, I learned to communicate using the complex rules of two languages during my childhood. I looked at the world with wonder, while adapting and making sense of it by remembering its complexities. But as I got older, I grew out of this ultra-powerful learning and memory, as most children do. What changes in our brains as we get older, and how do those changes affect our ability to learn?

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Researchers have known that NMDA receptors (NMDARs), certain types of glutamateThe principal excitatory neurotransmitter in the nervous sys... More receptors, are the predominant devices for controlling synaptic plasticity and memory functions in the hippocampusStructure in temporal lobe that has many functions but is es... More, an area of the brain that is important in the consolidation of information from short term memory to long term memory. NMDARs are made up two types of smaller subunits: NR2A and NR2B. Children’s brains have more NR2B subunits, which lengthen and strengthen synaptic connections between neurons to help kids form a lot of long-term memories. As kids age, the population of NR2B receptors subunits are progressively outnumbered by NR2A subunits. Could this switch account for the changes we experience in our memory as we age?

NMDAR subunits
The NMDA receptor forms a heterotetramer between two NR1 and two NR2 subunits. Its activation depends on binding of both glutamate and glycine.

A new study from Georgia Regents University published in this month’s edition of Nature Scientific Reports, offers some new insights about the way we remember information as we age. Researchers generated a transgenic mouse line that overexpressed NR2A receptor subunits to match the adult brain even when the mice were young. These mice had normal basic behaviors and short-term memory, but exhibited broad long-term memory deficits as revealed by several behavioral paradigms.

In novel object recognition tests, mice and rats tend to spend more time interacting with a new object, rather than one previously encountered, so it is used to assess memory of interaction with new objects. The transgenic mice with a higher proportion of NR2As could learn, remember, and retrieve the memory of the older object on the short-term just like the wild-type mice. However, they were impaired in long-term object recognition memory and were unable to distinguish between the novel object and the familiar object after 24 hours of the initial learning. Similar results were observed in fear conditioning memory tests, which is also used to test memory. The transgenic mice were impaired in turning both short-term contextual and cued fear memories into long-term memories regardless of whether the fear conditioning occurred in hippocampal-dependent or hippocampal independent manner.

Novel Object Recognition Test
The Novel Objection Recognition Test is used to assess memory for interactions with novel objects. In this case, the mouse is first presented with the red circles, and later presented with the blue square. A normal mouse would explore the new blue square during the testing setup.

Together, these results demonstrate that high NR2A levels, like those found in adults, can selectively affect long-term memory formation. This is not necessarily a bad thing, however, as adults are still able make strong neural connections and short term memories. Adults simply cannot form long-term memories to the same degree as children, who have higher NR2B levels. Perhaps this is the brain’s way of saving the information that is truly significant. 

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Cui Z., Feng R., Jacobs S., Duan Y., Wang H., Cao X. & Tsien J.Z. (2013). Increased NR2A:NR2B ratio compresses long-term depression range and constrains long-term memory, Scientific Reports, 3 DOI: 10.1038/srep01036

Images adapted from Wikimedia (Sponge 1 and Sponge 2), and Taglialatela G., Hogan D., Zhang W.R. & Dineley K.T. (2009). Intermediate- and long-term recognition memory deficits in Tg2576 mice are reversed with acute calcineurin inhibition, Behavioural Brain Research, 200 (1) 95-99. DOI: 10.1016/j.bbr.2008.12.034.

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