Researchers switch emotion linked to memory
Recalling an emotional experience, even years later, can bring back the same intense feelings. Researchers from the RIKEN-MIT Center for Neural Circuit Genetics revealed the brain pathway that links external events to the internal emotional state, forming one memory by engaging different brain areas. The study published in the journal Nature, also demonstrates that the positive or negative emotional valence of memory can be reversed during later memory recall.
The research team, led by Dr. Susumu Tonegawa, was interested in how brain structures like the hippocampus and the amygdala collaborate to form memories. In particular, they wanted to know whether the emotional valence - which describes the attractiveness or averseness of an emotion as positive or negative, and is thought of as an internal state of a person - is stored in the same place in the brain as the memory of an event that caused the emotion.
“Both the hippocampus and the amygdala are considered critical for memory formation. We wanted to know whether the memory engram was free to associate with positive or negative valences or whether it was fixed with respect to emotion,” said Roger Redondo, who along with Joshua Kim is co-first author of this study. “We also wanted to know at what point in the circuit the valence is assigned to the engram, in the hippocampus or the amygdala.”
In the experiment, mice were placed in a novel chamber and some were given a mild foot shock, while others were allowed to socialize with a female mouse, forming either a fear or a rewarding memory. The researchers were able to genetically label neurons that were active during the formation of either memory. The same neurons were then activated using optogenetics - a technique that harnesses light-sensing machinery from microbial organisms to precisely control activity of specific brain cells using pulses of light. Depending on the valence of the initial experience, the researchers could judge from the mouse’s behavior whether the activated memory was a fearful or a rewarding one by whether the mice avoided or were attracted to a particular location in the chamber where the memory neurons were optogenetically activated.
“If our technology drives memory engrams, it should work independently of whether the valence is negative or positive,” explained Dr. Redondo. “We wanted to show that the memory reactivation was not restricted to fear memories, as we had used in the past.”
To address the question of where in the brain the memory of an event and its emotional valence are stored, the researchers attempted to switch the valence of memories in mice from negative to positive and vice versa. The mice were given a new experience of the opposite valence while the researchers simultaneously activated the original memory in either the hippocampus or the amygdala. As a result, the memory engram stored in the hippocampus could change its valence. Mice who originally received foot shocks no longer showed fear when recalling that experience. Conversely, mice that originally socialized with a female now showed fear. The valence of the memory engram in the amygdala, on the other hand, could not be altered.
Thomas B. Czerner, in What Makes You Tick? The Brain in Plain English (2001), describes the amygdalae as “almond shaped” structures. The amygdalae are nestled and protected within each temporal lobe. The temporal lobe is located behind the temples, thus its name.
In Descartes’ Error: Emotion, Reason, and the Human Brain (1994), Antonio R. Damasio explains that “the first hint that amygdale and emotion might be related can be found in the work of Heinrich Klüver and Paul Bucy, who showed that surgical resection of the part of the temporal lobe containing the amygdala created affective indifference, among a variety of other symptoms.”
Brain anatomy: the amygdala location in the brain’s temporal lobe. In Evolving Brains (2000), John Allman cites research that shows when the amygdalae are damaged, one loses the ability to discern emotions, particularly fear and anger expressed in another’s face or intoned in another’s voice. Allman writes: “The role of the amygdale in the perception of facial expressions was beautifully shown by Ralph Adolphs and his colleagues, who studied a remarkable patient who had suffered a bilateral amygdalar damage without significant injury to other parts of the brain. Although this patient had normal vision and could perceive faces, she was unable to discriminate the emotional content in the negative facial expressions of fear and anger. Thus all faces appeared to be smiling or neutral to her, even those which were actually frightened or angry.” Damage to the amygdalae also impair one’s ability to descern emotion in another’s speech. Allman writes: “Sophie Scott and her colleagues found that amygdalar lesions also disrupted the ability to perceive the emotional content of speech intonation even though their patient had normal hearing. As with facial expressions in Adolphs’s patient, the auditory expressions of fear and anger were the most impaired in this patient.”
The researchers concluded that the hippocampal memory was neutral and could freely associate with either positive or negative emotions, while the amygdala is hard-wired for either negative or positive experiences. This study reveals an unanticipated flexibility in brain circuits during memory formation for emotional events. The findings may help explain the success of behavioral therapy for people with phobias or PTSD, and suggests the possibility of developing novel treatments for these and other disorders affecting emotions, such as depression, through manipulation of hippocampal memory cells.
The hippocampus, memory, and depression:
The term hippocampus is derived from the Greek word meaning “sea-horse,” which might somehow describe the shape of each hippocampal nucleus, although frankly, I do not see the resemblance. In the illustration to the left, I have added pink color to the hippocampus for clarity. You can see that it adheres to the curve of nerve fibers that curve once again to become the body of the fornix nerve pathway. This image links to its source, which includes a YouTube video on the anatomy of the hippocampus and surrounding structures.
The hippocampi- one in each hemisphere, extending to meet the amygdalae within the temporal lobes- are crucial for “forming, storing, and processing memory,” according to the MedlinePlus Dictionary. I should note here that the hippocampi are two of the first regions of the brain to suffer atrophy in Alzheimer’s disease. In the illustration to the right from the Journal of Neuroscience (links to source), the amygdala is colored red and the hippocampus is colored blue.
The MRI sagittal view to the left (links to source) shows the amygdala (labeled “A”) and the hippocampus (labeled “H”). In Brainscapes: An Introduction to What Neuroscience Has Learned about the Structure, Function, and Abilities of the Brain (1995), Richard M. Restak explains that “Fibers from all four lobes, along with association fibers uniting these separate connections into one unified experience, converge into the hippocampal region.” Restak writes: “Thanks to extensive two-way connections, with other brain areas the hippocampus and its immediate connecting structures integrate and coordinate both our outer- and inner-world experiences into a unity.” The hippocampi and other structures- such as the amygdalae- that process and integrate stimuli provide input to the autonomic nervous system (ANS; see ANS- the autonomic nervous system). So one can experience all the autonomic consequences of fear at the mere memory of a traumatic event.
Restak writes: “Damage to the hippocampus on both sides of the brain deprives the victim of the ability to learn new things and thus suspends the person in a time warp composed of the distant past, a present as thin and sharply etched as a knife blade, and an uncertain and fearful future. This happens because under normal circumstances we are able to maintain our sense of identity- who we are- only by forming new memories from moment to moment and accessing old ones at a leisurely command.”
Another example of kindling, which we discuss above, is the effects of stress on the hippocampi. In his 1995 New York Times article titled, “Severe Trauma May Damage the Brain as Well as the Psyche,” Daniel Goleman explains that studies in rats and primates suggest that glucocorticoids are the culprit. Goleman quotes Robert Sapolsky, who explains that glucocorticoids “may be neurotoxic to the hippocampus at the massive levels that are released under extreme stress or during trauma. I’m talking about the levels you would see in a zebra running from a lion, or a person fleeing a mugger- a real physical life-and-death crisis- if it is repeated again and again as time goes on.”
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Jens Wilkinson
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