NEW YORK—A study has found that making a specific type of brain pattern last longer improves short-term memory in rats.
The study, entitled “Long-duration hippocampal sharp wave ripples improve memory,” was published in the June 14 edition of the journal Science, and addresses working memory. Working memory is the temporary activation of brain cells that happens as we tour a new neighborhood, for instance, and remember our way around later that day.
Led by researchers at NYU School of Medicine, the new study finds that signals created by neurons, called sharp wave ripples, are longer by tens of milliseconds and capture more information when an animal is learning about a new place than when in a familiar setting. When the research team artificially doubled the length of the signals involved in memory recall of the best route through a maze, rats with extended ripples were found to be 10-15 percent better at finding a sugary reward than rats without manipulated signals.
Stated György Buzsáki, M.D., Ph.D., the Biggs Professor in the department of Neuroscience and Physiology at NYU School of Medicine, “Our study is the first in our field that made artificial changes to intrinsic neuronal firing patterns in the brain region called the hippocampus that increased the ability to learn, instead of interfering with it like previous attempts. After decades of study, we finally understand the mammalian brain well enough to alter some of its mechanisms in ways that may guide the design of future treatments for diseases that affect memory.”
The study results revolve around nerve cells, which transmit electrical signals that coordinate memories. Buzsáki’s team discovered in recent years that sets of neurons fire within milliseconds of each other in rhythmic cycles, creating closely connected sequences of signals that can encode complex information.
This observed pattern – where hippocampal cells in different parts of the circuit fire together briefly – creates sharp wave ripples. The patterns are named for their shape when captured graphically by electro-encephalography (EEG). Buzsáki noted that the ripples represent the replaying and combining of fragments of learned information, part of the process that weaves them into an animal’s memory.
In the current study, the team designed experiments where the correct route to get sugary water alternated between the left and right arms of a maze, each time a rat was placed in it. To get their reward, the rats had to use working memory to recall which way they had gone on the previous trial, and choose the opposite way for the current trial.
Many studies in recent years have established that hippocampal place cells encode each room or arm of a maze when entered, and then fire again as rats or humans remember going there, or plan to go there again. The study authors recorded the firing of place cells as a rat performed the memory task in the maze, and predicted the route taken as reflected in the cell firing sequence captured in each sharp wave ripple.
To artificially double the duration of just the ripples made by rats’ brain cells during task-driven navigation, researchers engineered hippocampal cells to include light-sensitive channels. Shining light through tiny glass fibers activated neurons and added more neurons to the naturally occurring sequence, thereby encoding more detail of the maze.
“We discovered that long-duration ripples are increased in situations demanding memory in rats. Prolongation of spontaneously occurring ripples by optogenetic stimulation, but not randomly induced ripples, increased memory during maze learning. The neuronal content of randomly induced ripples was similar to short-duration spontaneous ripples and contained little spatial information,” says the study’s abstract. “The spike content of the optogenetically prolonged ripples was biased by the ongoing, naturally initiated neuronal sequences. Prolonged ripples recruited new neurons that represented either arm of the maze. Long-duration hippocampal SPW-Rs replaying large parts of planned routes are critical for memory.”
The study also found that the extended ripples enabled slower-firing neurons to be recruited into their sequences. The authors’ past studies had shown these sluggish neurons to have better plasticity, as something new is learned. In contrast, faster firing partners in a ripple tended to start the sequence regardless of which route the rat took. Buzsáki’s team has been building the case that such rigid neurons generalize across experiences, encoding the familiar (instead of the newfound) aspects of each newly encountered location.
“Our next step will be to seek to understand how sharp wave ripples can be prolonged by non-invasive means, which if we succeed would have implications for treating memory disorders,” added first author Antonio Fernandez-Ruiz, Ph.D., a postdoctoral fellow in Buzsáki's lab.