Lifting the veil on 'valence,' brain study reveals roots of desire, dislike

January 23, 2018, MIT
Different 3-D perspectives the basolateral amygdala show how neurons that project to regions cluster together, but are also intermingled with other types. Blue neurons project to the hippocampus, red to the central amygdala, green to the nucleus accumbens. Credit: Beyeler, Tye, et. al.

The amygdala is a tiny hub of emotions where in 2016 a team led by MIT neuroscientist Kay Tye found specific populations of neurons that assign good or bad feelings, or "valence," to experience. Learning to associate pleasure with a tasty food, or aversion to a foul-tasting one, is a primal function key to survival.

In a new study in Cell Reports, Tye's team at the Picower Institute for Learning and Memory returns to the amygdala for an unprecedentedly deep dive into its inner workings. Focusing on a particular section called the basolateral amygdala, the researchers show how valence-processing circuitry is organized and how key neurons in those circuits interact with others. What they reveal is a region with distinct but diverse and dynamic neighborhoods where valence is sorted out both by connecting with other brain regions, and also by sparking cross-talk within the basolateral amygdala itself.

"Perturbations of emotional valence processing is at the core of many mental health disorders," says Tye, associate professor of neuroscience at the Picower Institute and the Department of Brain and Cognitive Sciences. "Anxiety and addiction, for example, may be an imbalance or a misassignment of positive or negative valence with different stimuli."

Despite its importance in both healthy behavior and psychiatric disorders, neuroscientists don't know how valence assignment really works. The new study therefore sought to expose how the neurons and circuits are laid out and how they interact.

Bitter, sweet

To conduct the study, lead author Anna Beyeler, a former postdoctoral associate in Tye's lab now a faculty member at the University of Bordeaux, France, led the group in training mice to associate yummy sucrose drops with one tone and nastily bitter quinine drops with another. They recorded the response of different neurons in the basolateral amygdala when the tones were played to see which ones were associated with the conditioned learned valence of the different tastes. They labeled those key neurons associated with valence encoding and engineered them to become responsive to pulses of light. When the researchers then activated them, they recorded the electrical activity not only of those neurons but also of many of their neighbors to see what influence their activity had in local circuits.

They also found, labeled, and made similar measurements among neurons that became active on the occasion that a mouse actually licked the bitter quinine. With this additional step, they could measure not only the neural activity associated with the learned valence of the bitter taste but also that associated with the innate reaction to the actual experience.

Later in the lab, they used tracing technologies to highlight three different kinds of neurons more fully, visualizing them in distinct colors depending on which other region they projected their tendrilous axons to connect with. Neurons that project to a region called the are predominantly associated with positive valence, those that connect to the central amygdala are mainly associated with negative valence, and they found that neurons uniquely activated by the unconditioned experience of actually tasting the quinine tended to project to the ventral hippocampus.

In all, they mapped over 1,600 neurons.

In Cell Reports Kay Tye's lab reveals the arrangement of neurons in the basolateral amygdala in circuits that encode valence and guide behavior. Credit: Picower Institute for Learning and Memory

To observe the three-dimensional configuration of these distinct neuron populations, the researchers turned the surrounding brain tissues clear using a technique called CLARITY, invented by Kwanghun Chung, Assistant Professor of Chemical Engineering and Neuroscience and a colleague in the Picower Institute.

Neighborhoods without fences

Beyeler, Tye and their co-authors were able to make several novel observations about the inner workings of the basolateral amygdala's valence circuitry.

One finding was that the different functional populations of neurons tended to cluster together in neighborhoods, or "hotspots." For example, picturing the almond-shaped amygdala as standing upright on its fat bottom, the neurons projecting to the central amygdala tended to cluster toward the point at the top and then on the right toward the bottom. Meanwhile the neurons that projected to the nucleus accumbens tended to run down the middle and the ones that projected to the hippocampus were clustered toward the bottom on the opposite side from the central amygdala projectors.

Despite these trends, the researchers also noted that the neighborhoods were hardly monolithic. Instead, neurons of different types frequently intermingled creating a diversity where the predominant neuron type was never far from at least some representatives of the other types.

Meanwhile, their electrical activity data revealed that the different types exerted different degrees of influence over their neighbors. For example, neurons projecting to the central , in keeping with their association with negative valence, had a very strong inhibitory effect on neighbors, while nucleus accumbens projectors had a smaller influence that was more balanced between excitation and inhibition.

Tye speculates that the intermingling of neurons of different types, including their propensity to influence each other with their activity, may provide a way for competing circuits to engage in cross-talk.

"Perhaps the intermingling that there is might facilitate the ability of these to influence each other," she says.

Notably, Tye's research has indicated the projections the different cell types make appear immutable, but the influence those cells have over each other is flexible. The may therefore be arranged to both assign valence, and also to negotiate it, for instance in those situations when a mouse spies some desirable cheese, but that mean cat is also nearby.

"This helps us understand how form might give rise to function," Tye says.

Explore further: Diametric brain circuits switch feeding and drinking behaviors on and off in mice

More information: Cell Reports (2018). DOI: 10.1016/j.celrep.2017.12.097

Related Stories

Diametric brain circuits switch feeding and drinking behaviors on and off in mice

March 22, 2017
Stress eating is something many people are familiar with, but how the brain links positive reinforcement like food to emotional states like fear or anxiety is not well-understood. The wiring in the mouse brain, however, is ...

Scientists identify brain circuit that drives pleasure-inducing behavior

March 22, 2017
Scientists have long believed that the central amygdala, a structure located deep within the brain, is linked with fear and responses to unpleasant events.

Neuroscientists identify brain circuits that could play a role in mental illnesses, including depression

March 31, 2016
Some mental illnesses may stem, in part, from the brain's inability to correctly assign emotional associations to events. For example, people who are depressed often do not feel happy even when experiencing something that ...

Neurons can be reprogrammed to switch the emotional association of a memory

October 24, 2014
Memories of experiences are encoded in the brain along with contextual and emotional information such as where the experience took place and whether it was positive or negative. This allows for the formation of memory associations ...

Neuroscientists identify two neuron populations that encode happy or fearful memories

October 18, 2016
Our emotional state is governed partly by a tiny brain structure known as the amygdala, which is responsible for processing positive emotions such as happiness, and negative ones such as fear and anxiety.

Recommended for you

New neurons in the adult brain are involved in sensory learning

February 23, 2018
Although we have known for several years that the adult brain can produce new neurons, many questions about the properties conferred by these adult-born neurons were left unanswered. What advantages could they offer that ...

Do you see what I see? Researchers harness brain waves to reconstruct images of what we perceive

February 22, 2018
A new technique developed by neuroscientists at the University of Toronto Scarborough can, for the first time, reconstruct images of what people perceive based on their brain activity gathered by EEG.

Neuroscientists discover a brain signal that indicates whether speech has been understood

February 22, 2018
Neuroscientists from Trinity College Dublin and the University of Rochester have identified a specific brain signal associated with the conversion of speech into understanding. The signal is present when the listener has ...

Study in mice suggests personalized stem cell treatment may offer relief for multiple sclerosis

February 22, 2018
Scientists have shown in mice that skin cells re-programmed into brain stem cells, transplanted into the central nervous system, help reduce inflammation and may be able to help repair damage caused by multiple sclerosis ...

Nolan film 'Memento' reveals how the brain remembers and interprets events from clues

February 22, 2018
Key repeating moments in the film give viewers the information they need to understand the storyline. The scenes cause identical reactions in the viewer's brain. The results deepen our understanding of how the brain functions, ...

Biomarker, clues to possible therapy found in novel childhood neurogenetic disease

February 22, 2018
Researchers studying a rare genetic disorder that causes severe, progressive neurological problems in childhood have discovered insights into biological mechanisms that drive the disease, along with early clues that an amino ...

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.