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An appetite map in the brain

Overview: Researchers report that the way the brain processes sensory input information depends on whether an animal lacks specific nutrients or is pregnant. The findings provide valuable new insight into the neural basis for behavior both within and outside food choices.

Source: Champalimaud Center for the Unknown

Let’s be honest. As tempting as the idea of ​​starting lunch with a chocolate cake may be, few would make that choice when it came down to it. And yet, at the end of the meal, many would reach for that same cake without hesitation.

The cause behind this phenomenon is the body’s ever-changing internal states: By lunchtime, the body often needs protein, so the brain favors that particular food choice. However, after the protein has been ingested, carbohydrates can be a nice extra to fill up the body’s fat stores.

But internal states are rarely one-dimensional. A person may be missing several nutrients (such as protein and salt) at the same time, as well as being pregnant, a condition that brings its own needs. How does the brain summarize these parallel internal states to direct behavior?

A study published today (July 6) in Nature provides new insight into this complex problem. “We show that the way the brain processes sensory input depends on whether animals lack specific nutrients or are pregnant,” said the study’s lead author Carlos Ribeiro, lead researcher at the Champalimaud Foundation in Portugal.

“Through this work, we have identified a general principle by which internal states are integrated to shape brain function and decision-making. In addition, the novel microscopy strategy we developed in this study may be valuable for understanding the neural basis of behavior, both within as outside the choice of food.”

Venture into unknown neural territory

To investigate how internal states shape behavior, Ribeiro’s team focused on a relatively poorly understood region of the fruit fly brain called SEZ (the subesophageal zone). This area is thought to play a critical role in food choice, as it receives the most taste input and houses the motor neurons that control nutrition. However, because this region consists mainly of closely entangled neural fibers, the anatomical substructure was not well defined.

To understand how it works, the team decided to create a “functional atlas” of the SEZ. In other words, they wanted to identify the substructures that make up this region and assign them specific functions. To that end, Daniel Münch, the study’s lead author, first expressed a fluorescent activity reporter in all neurons in the fly brain. He then performed advanced 3D neuroimaging in four groups of flies, each representing different internal states.

“We wanted to understand how two potent protein appetite modulators – protein deficiency and reproductive status – interact in the brain. We therefore defined four experimental groups: fully fed virgins, low protein virgins, fully fed mating flies and low protein mating flies. We recorded neural activity in the SEZ while the flies tasted sucrose, water and yeast (the fly’s natural protein source),” explains Münch.

An appetite card

The atlas the team created consists of 81 regions spread across the entire SEZ. These regions correspond to the majority of the previously described sensory and motor areas of the SEZ, and also include new, previously unidentified regions.

“Our atlas has captured some well-known regions. For example, one in the shape of a banana, which receives input from taste neurons located in the proboscis (the fly’s mouth),” said Munch.

“We also discovered a winged area that we called the Borboleta region (the Portuguese word for butterfly) in the posterior part of SEZ. This region later turned out to play a key role in stimulating protein requirements.”

In addition to identifying new regions, the atlas also revealed the effect of internal state on neural activity, pinpointing the “Borboleta region” as a protein appetite driver. The responses to water and sucrose hardly changed between the four groups. However, protein-rich diets had a striking effect.

“Protein-rich food-induced activity was greatly increased in large areas of the SEZ in non-protein animals. However, mating mainly affected activity in the motor regions of the SEZ.

“This was somewhat surprising, because mating and protein deficiency are both known to increase protein requirements, and so we didn’t expect to find such different response patterns,” Munch said.

They also witnessed the synergistic effect that combined internal states have on neural activity. “Mated, low-protein females had the highest activity in the motor regions of the SEZ,” Münch explained.

This shows the appetite map
Using a unique microscopy method, scientists identify key neurons that control protein cravings during pregnancy and under dietary restrictions in fruit flies. Credit: Ribeiro lab, Champalimaud Foundation.

“This means that although this pair of coexisting internal states — protein deficiency and pregnancy — are processed in different neural circuits, they eventually converge in the same area to promote protein requirement.”

Manipulating neurons to induce protein cravings

The team identified new regions in the SEZ and saw how different tastes and internal states influence neural activity in these regions. But how could they know if these areas are actually involved in boosting food preference?

“Then we turned to our newly discovered borboleta region, where protein taste elicited robust neural activity,” Munch said. “We reasoned that if it’s really involved in this behavior, we could influence protein requirements by artificially activating neurons in this region.”

The team aligned the atlas they created with another pre-existing atlas that maps the innervation patterns of groups of neurons. They then selected neurons in the borboleta region and activated them in fully fed flies, which normally prefer sucrose over protein. This manipulation resulted in a marked increase in protein requirement.

“We felt like the circle had come full circle: from observation to function,” Münch recalls.

“First, we observed food preference in the four groups of flies, noting that low-protein and paired flies have a high preference for protein. We then imaged neural activity in the SEZ, created the atlas and identified new regions. Finally we confirmed that one of these regions is involved in generating the behavior we initially observed by manipulating its activity.”

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“Overall, our approach allows identifying and linking neurons to specific behaviors, related to food choice and possibly others,” Ribeiro added.

“It would be difficult to implement our approach in any system other than fruit flies. The tools we have today make the fruit fly an amazing experimental system that allows us to dissect how the brain works. Importantly, the SEZ is similar to the brain stem of vertebrates.

“Our results therefore have broad implications for neuroscience. They may also inspire future studies aimed at bridging brain-wide activity mapping with functional circuit dissections. These are exciting times to be a neuroscientist,” he concluded.

About this news about appetite research

Author: press office
Source: Champalimaud Center for the Unknown
Contact: Press Agency – Champalimaud Center for the Unknown
Image: The image is attributed to the Ribeiro lab, Champalimaud Foundation

Original research: Closed access.
The neuronal logic of how internal states determine food choiceby Carlos Ribeiro et al. Nature


Abstract

The neuronal logic of how internal states determine food choice

When deciding what to eat, animals evaluate sensory information about food quality in addition to multiple ongoing internal states

How internal states interact to alter sensorimotor processing and form decisions such as food choice remains poorly understood. Here we use pan-neuronal volumetric activity imaging in the brain of Drosophila melanogaster to investigate the neuronal basis of internal state-dependent nutrient appetites.

We created a functional atlas of the ventral fly brain and found that the metabolic state shapes sensorimotor processing in large areas of the neuropil. The reproductive state, on the other hand, works locally to determine how sensory information is translated into powering motor output. Thus, these two states synergistically modulate protein-specific food intake and food choice.

Finally, using a novel computational strategy, we identify driver lines that label neurons innervating state-modulated brain regions and show that the newly identified ‘borboleta’ region is sufficient to direct food choice toward protein-rich foods.

We thus identify a generalizable principle by which different internal states are integrated to shape decision-making and propose a strategy to discover and functionally validate how internal states shape behavior.

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