The Neuroscience of Fearful Memories and Avoidance Behaviors

Hippocampal place cells house fearful experiences and drive avoidance behaviors

Posted Feb 20, 2017

Ji Lab/Baylor College of Medicine
The Ji Lab at Baylor College of Medicine investigates how the neural circuits in the brain encode, consolidate, and retrieve memories using lab rats. 
Source: Ji Lab/Baylor College of Medicine

Specific neurons in the hippocampus (called “hippocampal place cells”) remember when and where your brain experiences a broad range of sensory stimulation and emotions, including fear. Hippocampal place cells also drive subsequent fear-based avoidance behaviors, according to a new rodent study from the Ji Laboratory at Baylor College of Medicine.

The February 2017 study, “Hippocampal Awake Replay in Fear Memory Retrieval,” was published online ahead of print today in Nature Neuroscience. This is the first time neuroscientists have identified specific patterns of electrical activity in the hippocampal place cells of lab rats associated with specific memories. In this case, the memory of a fearful experience. 

Hippocampal Place Cells Serve As a Type of 'Neural GPS' in the Brain

Hippocampal place cells are activated anytime a human or animal moves within and between locations. These place cells keep track of everywhere your body goes and tag each location with a specific neural code that includes sensory perceptions based on stimuli that evoke pleasure, pain, reward, etc. 

All animals (including humans) seek pleasure and avoid pain. Therefore, it makes sense that when hippocampal place cells tag a specific location as being associated with physical or psychological pain, parts of the brain become hardwired to avoid this location. From an evolutionary standpoint, learning to avoid life-threatening environments is key to any species' survival. 

At the beginning of this new experiment, the researchers inserted tiny probes to monitor the electrical activity generated by neurons in the hippocampus. Then, they conditioned a fearful memory by exposing lab rats to mild foot shocks in a specific ‘shock zone’ as the rats explored a troughlike track. Lastly, the researchers observed neural activity in hippocampal place cells as each lab rat was placed back on the track and began to explore.

The researchers found that specific place cells linked to the 'shock zone' were reactivated anytime a rat got close to the place where foot shocks had been administered. The anticipatory thought of getting a shock appeared to trigger avoidance behaviors that caused the rodents to bypass the shock zone and avoid crossing the fearful path.

According to the abstract of this study, the fear reactivation of place cells occurred in “ripple-associated awake replay” of the exact location linked to a cell sequence that had been encoded along the path in the shock zone.

These findings reveal a specific hippocampal place-cell pattern underlying inhibitory avoidance behavior. This study also provides strong evidence for the involvement of “awake replay” in fear memory retrieval.

In recent years, a few different neuroscientific studies have reported that hippocampal place cells play a central role in storing location data and forming episodic memories. However, exactly how 'place cells' retrieve memories associated with a particular place—and subsequently drive avoidance behaviors—has remained a mystery until now. 

In a statement, Daoyun Ji, associate professor of molecular and cellular biology at Baylor College of Medicine, described the recent findings from his lab:

"Our laboratory rats cannot tell us what memory they are recalling at any particular time. To overcome that, we designed an experiment that would allow us to know what was going on in the animal's brain right before a certain event.

Interestingly, from the brain activity we can tell that the animal was 'mentally traveling' from its current location to the shock place. These patterns corresponding to the shock place re-emerged right at the moment when a specific memory is remembered.

We are also interested in determining how the spiking patterns of place neurons in the hippocampus can be used by other parts of the brain, such as those involved in making decisions."

This study from Daoyun Ji's Lab breaks new ground by discovering that milliseconds before a lab rat decides to avoid going back to a place where it previously had a fearful experience, the brain is recalling specific memories associated with the exact physical location where the fearful experience occurred.

Do You Have a Fearful "Room 101" Equivalent That Your Hippocampal Place Cells Avoid? 

Like most people, I have an innate fear of rats. Staring at the enlarged image of the rat below evokes a slight fear-based response and is probably encoding my hippocampal place cells to the place I'm sitting now as I stare at this image while typing this blog post. Your hippocampal place cells are probably being activated, too. If this image makes you uneasy or sticks in your mind, it will most likely be linked to when and where you are reading this by your hippocampal place cells. 

Ji Lab/Baylor College of Medicine
Source: Ji Lab/Baylor College of Medicine

Zooming in on this potentially menacing image of a rat from Ji's Lab barreling down a track towards the viewer triggers flashbacks in my mind's eye to the torture chamber "Room 101" from George Orwell's 1984

While being brainwashed by the Thought Police in Room 101, Winston Smith (the protagonist in 1984), must confront his biggest fear: A wire cage that fits snuggly on a person's head with a trap door that houses two very large (and ravenous) rats eager to devour the cage wearer's face.

Hypothetically, if Winston Smith's hippocampal place cells could be measured in Ji's neuroscience laboratory, Room 101 would evoke fearful memories and avoidance behaviors much like the lab rats who steered clear of the 'shock zone' in their habitrail. 

A Better Understanding of Hippocampal Place Cells Could Help Treat Dementia and Alzheimer's Disease

The next goal of Ji and his colleagues is to investigate whether the hippocampal spiking patterns they identified are absolutely required to guide (or misguide) human and animal behavior.

The researchers also plan to explore what role spiking patterns in the hippocampus might play in diseases that involve memory loss, such as Alzheimer's disease. Stay tuned for more cutting-edge research on hippocampal place cells in the months and years ahead. 

References

Chun-Ting Wu, Daniel Haggerty, Caleb Kemere, Daoyun Ji. Hippocampal awake replay in fear memory retrieval. Nature Neuroscience (2017). DOI: 10.1038/nn.4507