Dr. Bruce McNaughton (left) and Dr. Robert Sutherland (right). (Supplied by University of Lethbridge)

By David Opinko

U of L neuroscientists get nearly $1-million to test idea in memory formation

Oct 20, 2020 | 10:58 AM

LETHBRIDGE, AB – A pair of researchers at the University of Lethbridge hope to unlock answers about how long-term memories are formed and to open up new avenues for therapeutic treatments.

Drs. Bruce McNaughton and Robert Sutherland received a grant of $918,000 over five years from the Canadian Institutes of Health Research in hopes of helping people with Alzheimer’s or who have other memory-related conditions.

“The main point of the project grant is to test an idea about the organization of long-term memory that’s never been directly tested before,” says Sutherland. “We have had a long, long interest in trying to understand this particular process. It’s relevant to aging, dementia, and almost any kind of failure of long-term memory.”

He explains that there are two systems involved in the memory formation process, the hippocampus (short-term memory) and the neocortex (long-term memory).

“The real trick in trying to understand how long-term memories work is trying to understand how these two systems interact,” says Sutherland. “We know, for example, that when the interaction between the cortex and the hippocampus becomes rather weak, there’s a correlated memory problem. So, it could well be that this is an early problem in age-related memory decline or perhaps even some dementias.”

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The researchers observed a replay phenomenon in the hippocampus of rodents called sharp wave ripples. This occurred when the animals learned a certain task and while they were sleeping.

As one example they gave, if the rodents were running from one room to another while learning a task, the hippocampus repeats the same sequence of activity during the sharp wave ripple events while at rest or asleep.

“The idea that’s been kicking around for quite a while in various models of how long-term memory could work is that somehow that replay strengthens the representation of information outside the hippocampus, and in particular, in other parts of the cortex,” adds Sutherland.

The specifics for what you ate for breakfast, for instance, are replayed in the hippocampus during rest or sleep. In the neocortex, the memory system extracts the information and inter-leaves it with other information about what you are likely to eat for breakfast.

“The long-term memories stored in the cortex are partly distinct memories, but more often than not, it’s kind of a semantic or schematic representation of how the world works,” says McNaughton. “We hypothesize this storage of general knowledge about the world is constructed by amalgamating and extracting the gist of many episodes.”

“These cortical and hippocampal replays are thought to be shuffled together during rest and sleep, like a deck of cards, except that the number of old patterns exceeds the numbers of recent ones, of course,” McNaughton continues. “What’s happening during this replay is the cortex is kind of re-evaluating its assumptions about the world.”

While scientists know that interfering with sleep can impede memory storage, testing to see if these patterns of activity are necessary for memory formation is more difficult.

Sutherland and McNaughton have devised a way to test it in rodents by disrupting the sharp wave ripple and K-complex patterns using weak electrical stimulation of brain circuits.

If successful, they hypothesize that this form of electrical stimulation could be used in therapeutic settings to help those struggling with memory loss.