Lost memories aren’t so lost: Optogenetics sheds light on memory mystery

Susanna Pilny for redOrbit.com – Your Universe Online

Results from a new study indicate that a widely accepted theory of memory may just have to be forgotten.

The majority of neuroscientists tended to agree: Retrograde amnesia—in which one has memories of the past but can no longer remember them thanks to trauma, stress, or brain injury—is caused by damage to the neurons which stopped the memories from being stored.

New evidence, however, suggests that the majority is wrong. According to a study out of the RIKEN-MIT Center at the Picower Institute for Learning and Memory, retrograde amnesia is caused by a sort of recall impairment—meaning that the memory is still stored but can’t be accessed.

And they reached their conclusion by shedding a little light on the subjects.

Lux fiat

Optogenetics involves changing the DNA of animals so that their neurons fire when light is shined upon them.

“Over a decade ago, it was impossible to study neural activity in the brain while being able to manipulate these neurons during animal behavior. Today, optogenetics has revolutionized neuroscience allowing researchers to design rigorous and sophisticated experiments that were unimaginable in the past,” Dheeraj Roy, one of the lead authors on the paper, told redOrbit via email.

The RIKEN-MIT group had already used this technique to prove that memory engram cells (groups of neurons that store a memory) exist, and are found in the “memory part” of the brain—the hippocampus.

But there was another major memory theory that hadn’t been attempted, involving a process called long-term potentiation (LTP).

“When the brain encodes a memory, there are patterns of neural activity observed across several structures among which the hippocampus is widely considered to be essential. These activity patterns between connected neurons lead to long-lasting modifications that help increase signal transmission for future neural activity. This process of synaptic strengthening is referred to as long-term potentiation or LTP,” explained Roy.

To test whether or not the strengthening between neurons occurs, the researchers first located a group of neurons in a mouse hippocampus that expressed a memory upon exposure to light. Then, they activated the cells further, to see if the neurons would strengthen their connections upon further activation, with exciting results.

“We were able to demonstrate for the first time that these specific cells — a small group of cells in the hippocampus — had undergone this augmentation of synaptic strength,” said Susumu Tonegawa, the director of the RIKEN-MIT Center.

It was further examination of LTP that brought forth the amnesia discovery.

What’s my age again?

The researchers then decided to block long-term potentiation in the mice by administering anisomycin—a drug that blocks the protein synthesis required to strengthen the neuronal connections—immediately following the formation of a new memory.

A day later, they were unable to trigger the new memory using normal means (in this case, emotion)—but the memory cells weren’t destroyed. “So even though the engram cells are there, without protein synthesis those cell synapses are not strengthened, and the memory is lost,” said Tonegawa.

When light was shown on the neurons, however, the mice appeared to recall the entire memory—thus showing that the retrograde amnesia did not affect memory storage (as the memory still existed), but instead interfered with trying to retrieve it from the brain.

“The strengthening of engram [memory] synapses is crucial for the brain’s ability to access or retrieve those specific memories, while the connectivity pathways between engram cells allows the encoding and storage of the memory information itself,” said Tomas Ryan, one of three lead authors on the publication.

In short: A memory is stored in a group of neurons, and with the strengthening of the connections between them, you are more likely to be able to recall that memory. Retrograde amnesia means that you probably still have the memory, but you just can’t get to it.

So what’s next?

In the amnesiac mice, the light stimulation did not restore the “lost” memories—while they continued to exist, the mice were not able to access them through normal (in this case, emotionally-induced) means, and Roy says that is one of their future directions—permanent restoration of the memory. “In addition, it would be extremely useful to apply these strategies to other experimental and clinical cases of amnesia, such as Alzheimer’s disease,” he added.


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