A master gene that controls the complex process of memorizing events that an individual experiences has been identified by neuroscientists.
When a person experiences a new event, their brain encodes a memory of it by altering the connections between neurons. This requires turning on many genes in those neurons.
AdvertisementResearchers led by Yingxi Lin from the Massachusetts Institute of Technology (MIT) focused on the Npas4 gene, which previous studies have shown is turned on immediately following new experiences.
The gene is particularly active in the hippocampus, a brain structure known to be critical in forming long-term memories.
Lin and her colleagues found that Npas4 turns on a series of other genes that modify the brain's internal wiring by adjusting the strength of synapses, or connections between neurons.
"This is a gene that can connect from experience to the eventual changing of the circuit," Newswise quoted Lin as saying.
To investigate the genetic mechanisms of memory formation, the researchers studied a type of learning known as contextual fear conditioning in which mice receive a mild electric shock when they enter a specific chamber. Within minutes, the mice learn to fear the chamber, and the next time they enter it, they freeze.
The researchers showed that Npas4 is turned on very early during this conditioning.
"This sets Npas4 apart from many other activity-regulated genes.
"A lot of them are ubiquitously induced by all these different kinds of stimulations; they are not really learning-specific," she said.
Furthermore, Npas4 activation occurs primarily in the CA3 region of the hippocampus, which is already known to be required for fast learning.
"We think of Npas4 as the initial trigger that comes on, and then in turn, in the right spot in the brain, it activates all these other downstream targets. Eventually they're going to modify synapses in a way that's likely changing synaptic inhibition or some other process that we're trying to figure out," Kartik Ramamoorthi, the lead author of the study, said.
Npas4 is a transcription factor, meaning it controls the copying of other genes into messenger RNA - the genetic material that carries protein-building instructions from the nucleus to the rest of the cell.
The MIT experiments showed that Npas4 binds to the activation sites of specific genes and directs an enzyme called RNA polymerase II to start copying them.
"Npas4 is providing this instructive signal.
"It's telling the polymerase to land at certain genes, and without it, the polymerase doesn't know where to go. It's just floating around in the nucleus," he added.
When the researchers knocked out the gene for Npas4, they found that mice could not remember their fearful conditioning. They also found that this effect could be produced by knocking out the gene just in the CA3 region of the hippocampus. Knocking it out in other parts of the hippocampus, however, had no effect.
The study has been published in Science.
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