Summary: Our memories don’t flow in a continuous stream. They are broken down into key events by a small area of the brain called the locus coeruleus. New research suggests that this region acts as a kind of “reset button”: It activates at the boundaries of events, signaling the hippocampus to store separate memories.
Using functional magnetic resonance imaging (MRI) and pupillary measurements, scientists discovered that this mechanism is weakened by chronic stress, reducing the brain’s sensitivity to change and disrupting memory organization. Understanding this process could lead to better treatments for memory-related disorders such as PTSD and Alzheimer’s disease.
Important facts:
- Using the locus coeruleus, we can divide life into discrete and memorable events.
- Chronic stress causes hyperactivity of this area, which affects memory organization.
- Using this system could improve the treatment of post-traumatic stress disorder and Alzheimer’s disease.
Source: UCLA
Life may be a seamless flow, but our memories tell a different story.
We don’t remember the past as one long, uninterrupted text. We remember it as a series of significant events, such as the structure of sentences through grammar and punctuation.
Like any story, this organization gives shape and coherence to our experiences, helping us understand what happens and when. The brain must surely free up enough space for this difficult task, right? Wrong! It turns out that a small but powerful area attracts more than its own weight.
In a paper published in the journal Neuron, psychologists from UCLA and Columbia University combined brain imaging and pupillary measurements to show that a small group of neurons in the brainstem called the locus coeruleus acts as a “memory reset button” during important changes.
“Our main question was, as an experience unfolds, how does the brain know when an important memory ends and the next memory needs to begin?” said David Clavet, UCLA professor of psychology and lead author.
Research has shown that being in a stable context, such as the same room, links successive experiences in memory. In contrast, a change in context, or event boundary, transforms memories into distinct events.
We found that the locus coeruleus is most active at the event boundary when memories are triggered. So this small area at the heart of the brain’s arousal system can fuel our thoughts and memories.
Clavet and co-authors Ringo Huang of UCLA and Leila Davachi of Columbia University recruited 32 volunteers who viewed images of neutral objects in an MRI scanner. To determine whether the environment was stable or changing, simple tones were played in the right or left ear.
Eight pure tones were repeated in one ear to create the sense of a coherent event. The tone was then transferred to the other ear and modulated differently to create the perception of the extent of the event. This pattern of repetition and variation continued throughout the series, creating the perception of four separate auditory events.
The researchers analyzed how these pitch changes affected memory. They concluded that time provides a window into the formation of events: When people successfully form a sequence of events, it suggests that these elements are linked in a single memory. In contrast, it is more difficult to recall the exact order of events when they are stored in separate, distinct memories.
As predicted, locus coeruleus activation at event boundaries predicted later memory dissociation, as indicated by the impaired ability to recall the sequence of item pairs that crossed boundaries. The researchers also compared their measurements of locus coeruleus activation with measurements of pupil dilation taken at the same time. Pupils dilate slightly when new events occur and when the locus coeruleus is active.
These measurements confirmed that the observations made during fMRI effectively captured activation in this small area of the brain. Functional magnetic resonance imaging (fMRI) measures brain activity by detecting changes in blood flow while a person lies in a scanner.
The consequences of this neural signal and memory reset were far-reaching. Stronger activity in the locus coeruleus at the event boundary predicted more significant changes in activation patterns in the hippocampus, a region of the brain that registers contextual details such as space and time and is important for forming new memories.
Part of the role of the hippocampus is to map the structure of our experiences, providing an index of the beginning, middle, and end of events. We discovered that the locus coeruleus can send important “start” signals to the hippocampus, as if saying, “Hey, we’re in a new event!” says Davachi.
Previous studies have shown that increased locus coeruleus activity helps reprogram brain networks to focus on new and important experiences. Our results suggest that this updating signal is even more widespread, reaching memory-related regions that represent ongoing events. The researchers also examined how short bursts of locus coeruleus activity affected background levels of locus coeruleus activity.
This is important because neurons in the locus coeruleus function in two different modes: a burst mode that signals important events and forms new memories, and a background mode that regulates general alertness and stress.
“The locus coeruleus is like the brain’s internal alarm system,” says Clewett. The result is living with a fire alarm constantly going off, making it difficult to know when a fire is starting.”
Although the dynamic interaction between these activation patterns has been studied in the context of decision-making, cognition, and learning, their relevance to the way we understand and remember events remains unclear. Next, the authors investigated whether activation pulses (neural signals that separate memories) in the locus coeruleus at event boundaries could be reduced or lost during chronic stress. This question presented a challenge because fMRI alone is not sufficient to measure absolute stress levels or locus coeruleus activation.
To address this, they used an imaging method that indirectly measures neuromelanin, a colorful neurochemical that accumulates in the locus coeruleus and is repeatedly activated over time.
As predicted, participants with high neuromelanin-related signals, thought to indicate chronic stress, showed weaker pupillary dilation responses across event boundaries.
Strong, low-frequency fluctuations in locus coeruleus activation, an indicator of background activity levels, also predicted pupillary responses to weak peaks and troughs in locus coeruleus activation during the task. Taken together, these findings suggest that chronic hyperarousal may reduce sensitivity to change by disrupting the signals that anchor and organize new episodes in memory.
Identifying the locus coeruleus as a gateway or conduit for memory formation could help us better treat post-traumatic stress disorder (PTSD) and other memory-related disorders, such as Alzheimer’s disease, in which the locus coeruleus is abnormally overactive.
There are possible ways to calm an overactive locus coeruleus, for example taking medication, breathing slowly or squeezing pressure balls in the hands.
However, effective long-term solutions require further research, and will take time to discover and commercialize. Accurate event perception is directly linked to improved memory, suggesting that improving locus coeruleus function is an effective target for protecting or restoring memory.
The sophisticated equipment needed to study the brain requires funding that only the federal government can provide, Clavet said. He added that several NIH grants that funded the research, for example, funded the facilities used for the scans and experiments.
“Conducting clinical and basic science research is crucial to creating new options for treating debilitating diseases,” said Clavet.
Recent legislation threatens that future, not just for scientific research but for the progress that could improve the lives of patients and their families. It is perhaps ironic that, at a time when the legislation promises radical change, it turns out that one of the smallest factors in the brain can have the greatest impact on how we understand and remember our lives.
About this memory and neuroscience research news
Author: Holly Ober
Source: UCLA
Contact: Holly Ober – UCLA
Image: The image is credited to StackZone Neuro
Original Research: Open access.
“Locus coeruleus activation “resets” hippocampal event representations and separates adjacent memories” by David Clewett et al. Neuron
Abstract
Activation of the locus coeruleus ‘resets’ event representations in the hippocampus and separates adjacent memories.
Memories reflect the flow of experiences, capturing specific events in our lives. Using a combination of functional magnetic resonance imaging (fMRI), neuromelanin imaging, and pupillometry, we show that ongoing experiences of the locus coeruleus (LC) segment elicit arousal and activation in distinct memories.
As sequences unfold, encountering a change in context or event threshold activates pupil-associated arousal and LC processes that predict subsequent memory release.
Furthermore, boundaries promote the separation of temporal patterns within the dentate gyrus of the left hippocampus, which correlates with faster LC responses at these same transition points.
In contrast to transient LC effects, indirect structural and functional markers of increased background LC activation are associated with reduced excitability-related pupillary and LC responses at borders, suggesting that hyperactivation disrupts event distribution.
Our findings support the idea that excitatory mechanisms initiate neuronal and memory ‘resets’ in response to critical changes, thus fundamentally shaping the episodes that define episodic memory.
