Researchers from the University of Pennsylvania have taken a major step towards understanding how human long-term memories are formed.
The study focused on a group of proteins called nuclear receptors which have been implicated in the regulation of a variety of biological functions, including memory formation, the Daily Mail reported.
Nuclear receptors are a kind of transcription factor, proteins that can bind to DNA and regulate the activity of other genes.
Their regulatory role may be significant in memory formation, as gene transcription is required to turn short-term memories into long-lasting ones by strengthening neuronal synapses in the brain.
The team trained mice using a common method to create memories of a place and event, in which animals learn to associate a particular context or a certain tone with a specific experience.
Associations with a place or context are believed to be encoded in the hippocampus, while memories associated with a cue such as a tone are believed to be encoded in the amygdala.
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In the 24 hours after exposing mice to the initial training, the researchers examined expression patterns of all 49 nuclear receptor genes.
They found 13 that increased in expression in the hippocampus in the first two hours after training. Included in this group were all three members of a class of nuclear receptors called Nr4a.
The scientists next created a 'transgenic' mouse in which they could selectively block the activity of the three Nr4a genes.
When the researchers exposed the mice to the training context a second time, they found that the transgenic mice had reduced memory of the location where the training took place - memories that are located in the hippocampus - compared to normal mice.
In contrast, the mutant mice's amygdala-associated memories of a cue - the tone played during training - remained intact.
"The mice had impairment for contextual memory, which means something in the hippocampus is affected. That is the type of memory that goes away in Alzheimer's and schizophrenia," one of the researchers Ted Abel, Penn's Brush Family Professor of Biology, said.
The researchers also showed the mutant mice's short-term memory was not impaired. When trained in short-term memory tasks, their performance ranked similarly to their normal siblings.
The findings were published in the Journal of Clinical Investigation.