Npas4 Gene May Control Memory

Neurocientists at MIT have identified a master control gene for memory formation.  The work 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.

The researchers found that Npas4 turns on a series of other genes that modify the brain’s internal wiring by adjusting the strength of synapses - the connections between neurons.

Investigating the genetic control systems of memory formation, the researchers studied a type of learning known as contextual fear conditioning: 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 the Npas4 gene is turned on very early during this conditioning. “This sets Npas4 apart from many other activity-regulated genes,” Lin says. “A lot of them are ubiquitously induced by all these different kinds of stimulations; they are not really learning-specific.”

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,” says Kartik Ramamoorthi, a graduate student in Lin’s lab and lead author of the paper.

The MIT team also plans to investigate whether the same neurons that turn on Npas4 when memories are formed also turn it on when memories are retrieved. This could help them pinpoint the exact neurons that are storing particular memories.

“We’re hunting for the memory, and we think we can use Npas4 to mark where it is,” Ramamoorthi says. “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.



http://www.sciencemag.org/content/334/6063/1669