Scientists have identified more than 750 genes involved in long-term memory in worms, including many that had not been found previously.
The research at Princeton University aimed at finding ways to retain cognitive abilities during ageing.
"We want to know, are there ways to extend memory? And eventually, we would like to ask, are there compounds that could maintain memory with age?" said senior author Coleen Murphy, an associate professor of molecular biology and the Lewis-Sigler Institute for Integrative Genomics at Princeton University.
Researchers said the newly pinpointed genes are "turned on" by a molecule known as CREB (cAMP-response element-binding protein), a factor known to be required for long-term memory in many organisms, including worms and mice.
"There is a pretty direct relationship between CREB and long-term memory and many organisms lose CREB as they age," Murphy said.
By studying the CREB-activated genes involved in long-term memory, the researchers hope to better understand why some organisms lose their long-term memories as they age.
To identify the genes, the researchers first instilled long-term memories in the Caenorhabditis elegans worms by training them to associate meal-time with a butterscotch smell.
Trained worms were able to remember that the butterscotch smell means dinner for about 16 hours, a significant amount of time for the worm.
The researchers then scanned the genomes of both trained worms and non-trained worms, looking for genes turned on by CREB.
The researchers detected 757 CREB-activated genes in the long-term memory-trained worms, and showed that these genes were turned on primarily in worm cells called the AIM interneurons.
They also found CREB-activated genes in non-trained worms, but the genes were not turned on in AIM interneurons and were not involved in long-term memory.
CREB turns on genes involved in other biological functions such as growth, immune response, and metabolism. Throughout the worm, the researchers noted distinct non-memory (or "basal") genes in addition to the memory-related genes.
The next step, said Murphy, is to find out what these newly recognised long-term memory genes do when they are activated by CREB. For example, the activated genes may strengthen connections between neurons.
Worms are a perfect system in which to explore that question, Murphy said.
The worm Caenorhabditis elegans has only 302 neurons, whereas a typical mammalian brain contains billions of the cells.
"Worms use the same molecular machinery that higher organisms, including mammals, use to carry out long-term memory," said Murphy.
He said that future work will involve exploring CREB's role in long-term memory as well as reproduction in worms as they age.
