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Appetite-Controlling Brain Circuits in Mice May Explain Stress Eating

Curated by Claudia Shannon / Research Scientist / ishonest

Stress can influence our appetite in several ways. Short periods of stress can inhibit our appetite, but in the long run, too much stress can increase it, trigger food cravings, and cause weight gain.

Using a mouse model, new research examines the neuroscience behind stress eating, with a focus on the brain’s amygdala.

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The research was carried out by scientists at the Tonegawa Lab in Cambridge, MA. The laboratory, led by Susumu Tonegawa, is affiliated to the RIKEN-MIT Center for Neural Circuit Genetics – a collaborative effort between the Japanese RIKEN and the Massachusetts Institute of Technology.

The function of the brain’s amygdala

The amygdala – a small, almond-shaped region – is the brain’s emotional control center. The structure of the amygdala coordinates emotions, behavior, and motivation, and it is crucial to a person’s ability to process their own emotions, as well as recognizing them in other people.

The emotions primarily controlled by the amygdala seem to have a lot to do with survival. The amygdala generates the “fight-or-flight” response when we are confronted with danger, but it can also trigger other emotional responses when we are confronted with helpless children, potential sexual partners, or food.

Additionally, the amygdala is involved in memory. The small structure combines input from various areas, combining feeling with memory to create pleasant memories of a reward or unpleasant memories of a traumatic event.

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The new research by Tonegawa and colleagues shows that two opposing pathways in the amygdala serve to drive and suppress the appetite, as well as creating responses to fear-triggering stimuli.

Tonegawa and team recently conducted another study in which they identified neurons in the amygdala that are connected with positive and negative memories.

The researchers were able to see that the amygdala controls the response to positive and negative stimuli in a “push-pull manner.”

For this new research, the scientists used optogenetics to study the interactions between seven genetically different types of neurons in the central amygdala, and identified neural circuitry that runs across the basolateral and central areas of the amygdala.

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Optogenetics is a technique in which cells are genetically modified to be sensitive to light of a certain frequency. This technique allows researchers to follow the behavior of these cells.

‘Positive’ and ‘negative’ neurons promote or suppress appetite

The new study shows that these projections in the limbic system are very similar to the corticostriatal circuitry involved in motor function. The corticostriatal neuron projections have been associated with reward, cognition, and motivation.

“Our data suggest that the primary function of the [central amygdala] is for reward-related behaviors, rather than for fear-related behavior, as was believed in many previous studies.”

Susumu Tonegawa

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In the new research, Tonegawa and colleagues found that the previously identified neurons that respond to positive and negative stimuli in the basolateral amygdala also project into three other central areas in the amygdala. The communication between these different neurons in the central amygdala was found to promote or suppress reward-oriented behavior in mice.

Additionally, the study found different activation patterns in response to opposite stimuli. For instance, the scientists tested appetitive versus threatening stimuli – such as giving the mice food versus starving them, or giving them electric footshocks versus no shocks.

The neurons characterized as “positive” and “negative” in the scientists’ previous research were now shown to mediate pathways that boost or stop appetitive behavior. The genetic expression of these neurons was found in the Ppp1r1b and Rpso2 genes, respectively.

Furthermore, the scientists identified the genetic expressions of other neurons that regulate behavior. The Prkcd gene was found to play a key role in controlling defensive behavior. These neurons served to start or stop the freezing response in reaction to electric shocks.

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Drd1-expressing neurons in the central amygdala also played a crucial role in feeding and drinking.

In this study, the basolateral-to-central amygdala pathway was revealed to be structurally similar to the corticostriatal circuitry. Moreover, the study found that the same genetic markers work across opposing circuits in the amygdala.

This suggests that different parts of the brain are organized in a similar way, and that the same circuitry in the amygdala that is known to drive defensive responses to fear is also responsible for regulating appetitive behaviors.

Learn how chronic stress may raise obesity risk.

Read more on: brain, explain


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