Brain's quiet moments may shape memory and fight Alzheimer's

When neuroscientist Nuri Jeong flew home to South Korea, she expected a bittersweet reunion with her grandmother, whose Alzheimer’s disease had advanced to the point that close relatives said she no longer recognized them.

Yet, the moment Jeong walked in the door, her grandmother smiled in recognition. “I hadn’t seen her in six years, but she recognized me,” Jeong recalled.

“It made me wonder how the brain distinguishes between familiar and new experiences.” That question propelled Jeong into a years-long investigation of spatial learning.

The findings reveal that learning a place depends not just on firing bursts of excitatory neurons, but also on carefully timed lulls in a different class of cells: inhibitory parvalbumin interneurons, or PVs, which are located in the hippocampus.

Jeong is a former graduate researcher in the lab of Annabelle Singer in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. 

Learning’s unexpected pathways

Most work on spatial memory zeroes in on the excitatory cells that transmit electrical signals across the brain. Jeong and Singer flipped the script. They wondered whether moment-to-moment shifts in inhibition might control when, or even whether, new memories form.

“Think of PVs as a kind of circuit breaker that keeps our brain circuits from going haywire,” Singer explained.

“This research shows that inhibition isn’t static but plays a much more dynamic role in how we learn and remember. It isn’t just about putting the brakes on to keep our brains in check. It’s about precisely timing the release of inhibition to let the brain rapidly encode important information.”

The hippocampus – often called the brain’s GPS – was the ideal place to look. When mice explore, specialized “place cells” in the hippocampus fire in patterns that map out location. In classic theories, stronger place-cell firing equals stronger memory. Jeong suspected the real story was more nuanced.

Experiments test the brain’s memory

The researchers outfitted mice with tiny optical fibers and used optogenetics, shining pulses of light that could either quiet or activate PVs.

Thousands of neurons fired while the animals ran through a virtual-reality maze projected on surrounding screens. Hidden somewhere in the digital scenery was a reward. Each time a mouse discovered the prize, the software shifted its position, forcing the animal to learn again.

As the mice homed in on the reward zone, PV activity dipped. Crucially, that dip occurred before the animal actually reached the prize, hinting that the lapse in inhibition cleared a brief neural runway for new learning.

“We were surprised that PVs decreased their firing as animals approach a learned reward zone,” Singer said. “The decrease actually predicted the reward. This challenges the traditional idea that more neural activity always equates to learning.”

When the team prevented the PV lull – keeping inhibition high right up to the reward – the mice failed to learn. Without that fleeting slack in the neural chain, excitatory circuits apparently could not rewire.

New insights into Alzheimer’s

Singer believes the work reframes how neuroscientists view diseases marked by memory loss. “When we think of Alzheimer’s, we often think about an overactive brain,” she said.

“But it isn’t just a volume problem. It’s a timing and location problem. If inhibition isn’t decreasing in the right place at the right moments, the brain may struggle to form new memories.”

The findings suggest that therapies need not simply tamp down global overactivity; instead, they might target the precise micro-rhythms of inhibition.

Noninvasive brain stimulation protocols, for instance, could aim to nudge PVs into better-timed fluctuations, allowing excitatory networks to store memories again.

Learning after setbacks

Jeong’s own journey mirrors the seesaw of excitation and inhibition she studies. Before finishing her PhD in 2023, she survived an auto accident that paused her lab work for months. During recovery, she reflected on ways to bridge neuroscience and everyday performance.

She now runs a consultancy, Goals Unhindered, translating brain science into corporate training.

“But my first love was research,” Jeong said. “This study is a reminder for me that inhibition in the brain, like setbacks in life, isn’t just about stopping activity. It’s about learning and shaping new memories, and how we make our way in the world.”

The future of memory research

Singer’s group is already probing whether the same inhibitory timing breaks down in mouse models of Alzheimer’s. If so, it could explain why the disease derails navigation in real environments long before broader memory fades.

Beyond disease, the work reframes how neuroscientists understand learning itself. Rather than a simple matter of ramping neural engines faster, effective memory may hinge on brief, precisely placed silences – moments when the brain’s “circuit breakers” flick off just long enough for new wiring to fuse.

For anyone who has watched a loved one fade into dementia, that offers a sliver of hope. Understanding when and where to release the brain’s internal brakes may one day help scientists restore the rich maps of memory that make recognition – and reunion – possible.

The study is published in the journal Nature.

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