Scientists find a gene that controls memory formation

A team led by an Indian-origin neuroscientist has found a gene that ''turns on'' when memories are stored in the brain, a discovery they believe could help pinpoint the exact locations of memories in the brain.

It's known that when one witnesses a new event, the brain encodes a memory of it by altering the connections between neurons. This needs turning on many genes in those neurons.

Now, neuroscientists at the Massachusetts Institute of Technology (MIT) have identified a gene, called Npas4, which is very active in the hippocampus -- a brain structure known to be critical in forming long-term memories.

The findings, described in the journal Science, would be a breakthrough in pinpointing the exact locations of memories in the brain and might open up new avenues for altering or even creating memory, the researchers said.

"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," Kartik Ramamoorthi, a MIT graduate student who led the study, said in a statement.

"Eventually they are going to modify synapses in a way that's likely changing synaptic inhibition or some other process that we are trying to figure out," Ramamoorthi said.
The scientists, who carried out their research on mice, 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," said Yingxi Lin, a member of the McGovern Institute for Brain Research at MIT where the study was carried out.

The researchers gave mice 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 found 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," Lin said.So far, the researchers have identified only a few of the genes regulated by Npas4, but they suspect there could be hundreds more. The experiments showed that Npas4 binds to the activation sites of specific genes and directs an enzyme called RNA polymerase II to start copying them.

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 in the CA3 region of the hippocampus. Knocking it out in other parts of the hippocampus, however, had no effect.

Though they focused on contextual fear conditioning, the researchers believe that Npas4 will also prove critical for other types of learning.

"We're hunting for the memory, and we think we can use Npas4 to mark where it is," Ramamoorthi said.

"That's because it's turned on specifically and now we can label the cells and maybe fish out where in the brain the memory is sitting."