Study identifies how brain connects memories across time

May 23, 2016, University of California, Los Angeles
brain
Credit: public domain

Using a miniature microscope that opens a window into the brain, UCLA neuroscientists have identified in mice how the brain links different memories over time. While aging weakens these connections, the team devised a way for the middle-aged brain to reconnect separate memories.

The findings, which were published today in the advance online edition of Nature, suggest a possible intervention for people suffering from age-related problems.

"Until now, neuroscientists have focused on how the creates and stores single memories," said principal investigator Alcino Silva, a professor of neurobiology at the David Geffen School of Medicine at UCLA. "We wanted to explore how the brain links two memories and whether the passage of time affects the strength of the connection."

"In the real world, memories don't happen in isolation," said first author Denise Cai, a researcher in Silva's lab. "Our past experiences influence the creation of new memories and help us predict what to expect and make informed decisions in the future."

In an intricate experiment, the UCLA team tested in young and middle-aged whether the brain linked memories of experiences separated by five hours versus seven days.

Watching neurons in real time

The lab used a miniature microscope, called a Miniscope, which was developed by UCLA neuroscientists Dr. Peyman Golshani, Baljit Khakh and Silva with funding from the presidential BRAIN Initiative and the Geffen School. The instrument's powerful camera allowed the scientists to peer into the brains of young and observe their cells in action. The tiny, head-mounted microscope illuminated the animals' neurons firing as the mice moved freely in their natural environments.

For 10 minutes at a time, each mouse was placed in three boxes, all unique in terms of fragrance, shape, lighting and flooring. A week's time separated placement in the first and second boxes. Only five hours separated time spent in the second and third boxes, where the mouse later received a small shock to the foot.

Two days later, the team returned each mouse to all three boxes. As expected, the mice froze with fear when it recognized the inside of the third box.

What happened next, however, came as a surprise.

"The mouse also froze in the second box, where no shock occurred," Silva observed. "This suggests that the mouse transferred its memory of the shock in the third box to its experience in the second box five hours earlier."

When Silva and Cai examined the animals' brains, the neural activity confirmed their hypothesis.

"The same brain cells that recorded the mouse's shock in the third box also encoded its memory of the second box a few hours earlier," Cai said. "We saw 20 percent more overlap in the neural circuits that recorded the animal's experiences in the memories that unfolded closer in time."

In other words, says Silva, "The memories became interrelated in how they were encoded and stored by the brain, such that the recall of one memory triggered the recall of another memory related in time."

Exciting the brain

Based on an earlier Silva finding, the team knew that a cell is most likely to encode a memory when it's aroused and ready to fire. Neuroscientists refer to this condition as excitability.

"The excitable brain is already warmed up," Silva said. "It's like stretching your muscles before exercise or revving your car engine before you drive."

Suspecting that aging weakens neurons' ability to fully excite, the UCLA researchers conducted a similar experiment in middle-aged mice. They introduced each of the mice to two boxes, five hours apart, and administered a foot shock in the second box.

When they returned the animals to the boxes two days later, the results could not have been more clear-cut.

"The older mice froze only in the box where they had received a shock," Cai explained. "They did not react in the first box."

A glimpse into the Miniscopes confirmed that the brains of the mice did not connect the two memories; each memory was encoded on its own neural circuit.

Rescuing lost connections

Next the team focused on boosting the older animals' ability to link memories. Cai used a biological tool to excite neurons in a tiny part of the hippocampus—the memory center of the brain—before introducing the mice to the first box.

She stimulated the same cells before placing the mice in the first box and the second box, where they received a foot shock two days later.

"The proof in the pudding arrived when we reintroduced the middle-aged mice to the first box," Silva said. "The animals froze—they now linked the shock that happened in the second box to the first. This suggests that increased excitability had reversed their age-related inability to link memories."

Cai and Silva are currently testing an FDA-approved drug's effect on the ability of middle-aged mice to connect memories.

Explore further: 'Lost' memories can be found

More information: A shared neural ensemble links distinct contextual memories encoded close in time, Nature, DOI: 10.1038/nature17955

Related Stories

'Lost' memories can be found

March 16, 2016
In the early stages of Alzheimer's disease, patients are often unable to remember recent experiences. However, a new study from MIT suggests that those memories are still stored in the brain—they just can't be easily accessed.

Deep sleep puts the 'REM' in remembering

May 13, 2016
When it comes to mental health and cognitive function, the importance of rapid eye-movement sleep - that deep, restorative stage of sleep that we cycle in and out of throughout the night - is so well established that experiments ...

Researchers use optogenetics to cause recoding of mouse associative memory

February 23, 2016
(Medical Xpress)—A team of researchers working at Oxford University has for the first time, caused an external decoding of an associative memory in a mammal. In their paper published in the journal Nature Neuroscience, ...

Gene linked to Alzheimer's disease impairs memory by disrupting brain's 'playback system'

May 6, 2016
Scientists at the Gladstone Institutes have discovered how the major genetic risk factor for Alzheimer's disease causes memory impairment. A specific type of brain activity important for memory replay is disrupted in mice ...

How traumatic memories hide in the brain, and how to retrieve them

August 17, 2015
Some stressful experiences - such as chronic childhood abuse - are so overwhelming and traumatic, the memories hide like a shadow in the brain.

Researchers find neurons responsible for tying together fearful events with environment

February 21, 2014
(Medical Xpress)—Researchers working at Columbia University have identified a neuron that serves to tie fearful events with the environment in which they occurred. In their paper published in the journal Science, the team ...

Recommended for you

Leg exercise is critical to brain and nervous system health

May 23, 2018
Groundbreaking research shows that neurological health depends as much on signals sent by the body's large, leg muscles to the brain as it does on directives from the brain to the muscles. Published today in Frontiers in ...

Mechanisms of harmful overhydration and brain swelling

May 22, 2018
We are all familiar with the drawbacks of dehydration, but we rarely hear about the harmful effects of overhydration. For one, excess fluid accumulation can lead to dangerously low sodium levels in the blood or hyponatremia—a ...

Mice brain structure linked with sex-based differences in anxiety behavior

May 22, 2018
Using male individuals has long been a tradition in scientific mice studies. But new research enforces the importance of using a balanced population of male and female mice.

In brain stimulation therapy less might be more

May 22, 2018
One of the promising non-invasive brain therapeutic methods is the repetitive transcranial magnetic stimulation (rTMS). During such a procedure, a magnetic coil is placed near the head of the patient and a magnetic pulse ...

Subtle hearing loss while young changes brain function, study finds

May 22, 2018
Cranking up your headphones or scrambling for a front-row spot at rock shows could be damaging more than your hearing.

What helps form long-term memory also drives the development of neurodegenerative disease

May 22, 2018
Scientists have just discovered that a small region of a cellular protein that helps long-term memories form also drives the neurodegeneration seen in Amyotrophic Lateral Sclerosis (ALS). This small part of the Ataxin-2 protein ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.