The persistence of memory is crucial to our sense of identity, and without it, there would be no learning, for us or any other animal. It’s little wonder, then, that some researchers have called how the brain stores memories the most fundamental question in neuroscience.
A milestone in the effort to answer this question came in the early 1970s, with the discovery of a phenomenon called long-term potentiation, or LTP. Scientists found that electrically stimulating a synapse that connects two neurons causes a long-lasting increase in how well that connection transmits signals. Scientists say simply that the “synaptic strength” has increased. This is widely believed to be the process underlying memory. Networks of neural connections of varying strengths are thought to be what memories are made of.
In the search for molecules that enable LTP, two main contenders emerged. One, called PKMzeta (protein kinase Mzeta), made a big splash when a 2006 study showed that blocking it erased memories for places in rats. If obstructing a molecule erases memories, researchers reasoned, that event must be essential to the process the brain uses to maintain memories. A flurry of research into the so-called memory molecule followed, and numerous experiments appeared to show that it was necessary and sufficient for maintaining numerous types of memory.
The theory had a couple of holes, though. First, PKMzeta is short-lived. “Those proteins only last in synapses for a couple of hours, and in neurons, probably a couple of days,” says Todd Sacktor, a neurologist at SUNY Downstate Health Sciences University, who was co-senior author of the 2006 study. “Yet our memories can last 90 years, so how do you explain this difference?” Second, PKMzeta is created in cells as needed, but then it has to find the right synapses. Each neuron has around 10,000 synapses, only a few percent of which are strengthened, says neuroscientist Andre Fenton, the other co-senior author of the 2006 study, who is now at New York University. The strengthening of some synapses and not others is how this mechanism stores information, but how PKMzeta molecules accomplish this was unknown.
A new study published in Science Advances by Sacktor, Fenton and their colleagues plugs these holes. The research suggests that PKMzeta works alongside another molecule, called KIBRA (kidney and brain expressed adaptor protein), which attaches to synapses activated during learning, effectively “tagging” them. KIBRA couples with PKMzeta, which then keeps the tagged synapses strengthened.
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