• Fixed calls, flexible replies: Zebra finch contact calls are vocal abilities the birds are born with and cannot change – but the timing of their replies is flexible. New research shows it is shaped by social context: They respond faster, more often, and with more consistent timing to calls from a familiar bird.
• Neural signature of familiarity: More than two thirds of neurons observed in a key brain region for vocal timing responded to calls, with inhibitory interneurons firing more strongly for familiar callers.
• Broader significance: Even behaviors birds are born with are influenced by social context, raising new questions about how the brain controls vocal exchanges across species.

Conversations with friends have an ease that is hard to replicate with someone you have just met – often replies come more naturally and timing just seems to click. A strikingly similar pattern plays out in zebra finches, very sociable songbirds whose back-and-forth chatter with familiar individuals can take a noticeably different rhythm to exchanges with strangers. Now, researchers at the Max Planck Institute for Biological Intelligence have uncovered how this communication pattern is reflected in the brain, showing that social context influences the activity of neurons involved in vocal communication.

Innate flexibility

Zebra finches are one of the most widely studied songbirds in neuroscience, partly because they are one of the few animal species that, like humans, learn to vocalize by listening to others. Much of this research has focused on their songs, which males learn by copying adults. However, zebra finches also produce short contact calls in the form of simpler sounds that, unlike songs, the birds are born knowing how to make.

Previous studies have shown that when using these calls in social exchanges, the birds tend to contact call more often and more consistently with individuals they are familiar with. But what happens in the brain when a bird hears a familiar call, and how that might shape its reply, remained unclear. A team led by senior researchers Daniela Vallentin and Jonathan Benichov set out to find answers.

The team played zebra finches recordings from familiar and unfamiliar birds, and the birds replied more often, faster, and more consistently to familiar calls. When the team then studied what was happening in the brain, they found a clear neural counterpart.

“We have found that when zebra finches hear a familiar call, their brains respond differently to one from an unfamiliar bird,” says Carlos Gomez-Guzman, doctoral researcher and first author of the study, published in PLOS Computational Biology. “One of the things that surprised us was the sheer scale of the neuronal response: more than 70% of neurons in HVC, a region involved in controlling vocal timing, responded when birds heard a call — showing this region is not just involved in song, but is actively processing social calls too. Within that broad response, neurons called inhibitory interneurons, which help regulate whether and when a bird calls back, fired more strongly and for longer when the caller was familiar. It is not that calls from familiar birds sound particularly different, but when they recognise the call of an acquaintance the social bond between the birds is reflected in how the brain responds.”

How the brain tunes in

Zebra finches make for a fascinating window into vocal exchanges: like human speech, replies between birds typically follow in less than half a second. However, unlike us each bird’s contact call is something it’s born with and cannot reshape – what varies is when and how quickly it calls back.

To find out what was happening in the brain, the team recorded neuronal activity while birds listened to familiar and unfamiliar calls. HVC contains two key types of neurons – excitatory projection neurons, which send signals to other brain regions involved in song and vocal production, and inhibitory interneurons, which act locally, and can influence whether and when a bird initiates a call. Both types of neurons responded upon hearing any call, however interneurons showed a much higher sensitivity to familiarity, firing more intensely and for longer when the caller was known. This neural activity persisted into the window when a bird would normally reply, suggesting it could influence when the bird calls back.

“The strength of this neural activity closely matched how quickly and reliably the birds replied, and using machine learning to study the data we could even distinguish familiar from unfamiliar callers based on interneuron activity alone,” says Gomez-Guzman. “The study shows it is not just learned song that can be flexibly adjusted in communication – behaviors like contact calling, which birds such as zebra finches are born with, can be too”. That opens up fascinating questions: is this precise social timing itself something birds learn? How do these neurons interplay with those in other, evolutionarily older brain regions? Understanding how zebra finches manage this could shed light on why some species are so much better at vocal exchanges than others, and even give insights into the cognitive demands of holding a conversation – something we take for granted, but which requires the brain to listen, decide, and respond in a split second.

Social familiarity strengthens neural and vocal responses to conspecific calls in zebra finches Carlos M. Gomez-Guzman, Daniela Vallentin* & Jonathan I. Benichov*. PLOS Computational Biology, online 11 March 2026 Link

* co-senior authors

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• Researchers have discovered a specific group of nerve cells in the hypothalamus of the brain that influences eating behavior and weight gain.
• These nerve cells are controlled by the hormone leptin, which suppresses appetite
• Discovery offers the potential to develop further targeted treatments for obesity

Obesity is a global health problem that affects many people. In recent years, very promising anti-obesity drugs have been developed. Despite these successes, there are patients who do not respond to these drugs or suffer from side effects. Therefore, there is still an unmet need for therapies. Researchers at the Max Planck Institute for Metabolism Research have now discovered a small group of nerve cells in the hypothalamus of mice brain that influence eating behavior and weight gain. This discovery could pave the way for the development of targeted anti-obesity drugs.

The research group identified the so-called PNOC/NPY nerve cells in the brains of mice. When activated, these cells increase food intake and lead to obesity. Interestingly, these nerve cells are also present in the human brain. Using novel genetic and molecular biological tools, the researchers were able to analyze the neurons at the single cell level and divide them into different clusters. Within this large group of nerve cells, only one cluster is responsible for the observed eating behavior.

Removing Leptin Receptors

Previous studies have shown that PNOC neurons in the hypothalamus are particularly active when mice are fed a high-fat diet. In further analyses, the researchers found that around 10% of these nerve cells have a receptor for the hormone leptin. Leptin is produced in adipose tissue and suppresses appetite in the brain. If the leptin receptor in this cluster of PNOC nerve cells was removed, the mice ate more and became overweight.

“It was surprising that such a small group of nerve cells specifically leads to obesity,” explains Marie Holm Solheim, first author of the study.

The researchers plan to continue studying these nerve cells to identify additional specific targets for potential drugs and to make them amenable to pharmacological intervention.

We hope that drugs that act on this specialized group of nerve cells will offer promising alternative therapies,” says Jens Brüning, head of the study. “However, there is still a long way to go before these can be used.”

Marie H. Solheim, Sima Stroganov, Weiyi Chen, P. Sicilia Subagia, Corinna A. Bauder, Daria Wnuk-Lipinski, Almudena Del Río-Martín, Tamara Sotelo-Hitschfeld, Cait A. Beddows, Paul Klemm, Garron T. Dodd, Sofia Lundh, Anna Secher, F. Thomas Wunderlich, Lukas Steuernagel, Jens C. Brüning, Hypothalamic PNOC/NPY neurons constitute mediators of leptin-controlled energy homeostasis. Cell, June 2025 Link

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Summary:

• Birds, unlike humans, can sleep deeply with both halves of their brains (symmetrically) or with one half sleeping lighter than the other (asymmetrically).
• Study of European jackdaws led by an international team of researchers shows that when sleep-deprived, jackdaws were more likely to fall into deep sleep with both brain halves at the expense of keeping one half vigilant – especially early in the night, when the need to recover is greatest.
• Observing how birds navigate the trade-off between vigilance and sleep may help scientists better understand how sleep loss affects brain function more broadly, including in us.

As most people who have pulled an all-nighter will agree, lost sleep can leave us feeling foggy and far from our best. In some ways, birds respond similarly, often sleeping longer and more deeply after sleep loss. But unlike humans, birds can sleep with one eye open, keeping one half of the brain somewhat alert while the other sleeps deeply. This balance between vigilance and deep sleep helps them stay aware of danger while still getting some much-needed shut-eye. However, a new study of European jackdaws shows that this strategy has its limits: when sleep-deprived, these clever, social birds were more likely to fall into deep sleep in both brain halves – even at the cost of losing vigilance. The findings offer new insight into sleep and the consequences of going without it.

Keeping an eye out

Sleep is essential across the animal kingdom, but there is wide variation in how it happens. When humans sleep, our brains cycle through stages, alternating between rapid eye movement (REM) sleep and non-REM sleep roughly every 90 minutes. Birds go through these same stages, but typically in much shorter bursts – and their sleep patterns are far more flexible than ours. One weapon in their sleep armory is the ability to sleep with one eye open during non-REM sleep, a state known as asymmetric sleep. This is characterized by light sleep in the brain half connected to the open eye and deep sleep in the brain half connected to the closed eye. It allows birds, such as ducks, to keep one side of the brain more alert while the other enters a deeper state of sleep.

Non-REM sleep is thought to play a key role in memory consolidation and clearing waste from the brain. However, recharging one brain hemisphere with one eye open takes longer than resting both sides together in deep, symmetrical sleep. Scientists are still uncovering when, how, and why birds rely on this nap-time balancing act.

The new study of European jackdaws, led by researchers at the Max Planck Institute for Biological Intelligence and the Groningen Institute for Evolutionary Life Sciences, reveals a trade-off between getting sleep and staying alert. The findings, which tracked sleep patterns across several brain regions in nine jackdaws, are published today in Current Biology.

Previous studies have shown how birds and some other animals use adaptable, vigilant sleep strategies to stay alert in challenging situations – from great frigatebirds sleeping asymmetrically mid-flight, to mallard ducks keeping one eye open when vulnerable on the outer edge of their group, to northern fur seals sleeping asymmetrically when in the water. Even humans – who do not sleep with one eye open – tend to sleep more lightly with the left half of the brain on the first night in a new environment. This new research reveals where such strategies fall short: sleep-deprived jackdaws spent more time in deep, symmetrical sleep, while asymmetric sleep became less common – especially early in the night, when the need to recover is greatest.

“Sleep is a dangerous part of life for many animals, as it leaves them exposed to all kinds of risks,” says Niels Rattenborg, group leader at the Max Planck Institute for Biological Intelligence. “Some birds can function surprisingly well on far less sleep than we can, but even that strategy appears to have its limits. We have found that when they’re tired, jackdaws are more likely to sleep deeply – even if that means becoming more vulnerable. Observing how birds navigate the trade-off between vigilance and sleep may help us better understand sleep in general.”

Tracking tiredness

To investigate how European jackdaws recover from sleep loss – and how they switch between symmetric and asymmetric sleep – researchers studied nine birds using electroencephalograms (EEGs), which measure the activity of millions of neurons across the brain.

The researchers found that some brain areas slept more deeply than others, which may suggest that regions used more during wakefulness need deeper sleep. For example, not all parts of the jackdaws’ brains responded to sleep loss in the same way. Regions involved in vision and decision-making showed stronger signals after sleep deprivation, while others, like the memory-related hippocampus, were less affected.

“Our findings reveal that even the highly flexible sleep strategies used by jackdaws have limits,” says Peter Meerlo, a group leader at the Groningen Institute for Evolutionary Life Sciences. “That tells us something fundamental about sleep: it’s not just a passive state, but a behavior shaped by both evolution and environmental demands. The study offers a fresh perspective on how animals balance the need for sleep with the risk of predation or other threats – and could help us better understand how sleep loss affects brain function more broadly, including in humans.”

Sjoerd J. van Hasselt*, Dolores Martinez-Gonzalez*, Gert-Jan Mekenkamp, Alexei L. Vyssotski, Simon Verhulst, Gabriël J. L. Beckers, Niels C. Rattenborg$, Peter Meerlo$
*, $ These authors contributed equally.
Sleep pressure causes birds to trade asymmetric sleep for symmetric sleep. Current Biology, online 31 March, 2025 Link

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To ensure we get the calories and hydration we need, the brain relies on a complex network of cells, signals, and pathways to guide us when to eat, drink, or stop. Yet, much about how the brain deciphers the body’s needs and translates them into action remains unknown.

Researchers from the Max Planck Institute for Biological Intelligence, in collaboration with the University of Regensburg and Stanford University, have identified specific populations of neurons in the amygdala – an emotional and motivational center of the brain – that play a key role in this process. These specialized “thirst” and “hunger” neurons operate through distinct circuits, influencing the drive to eat or drink. The study, which was carried out in mice, sheds new light on the amygdala’s role in regulating our nutritional needs and may offer insights into eating disorders and addiction.

At the heart of the brain’s emotional centre

The amygdala, a brain region often linked to emotions and decision making, also plays a key role in shaping our desire to eat and drink. Earlier research led by Rüdiger Klein’s group at the Max Planck Institute for Biological Intelligence revealed that neurons in the central nucleus of the amygdala connect food to feelings – pairing tasty meals with positive emotions, associating bad food with aversion, and suppressing appetite when nausea sets in. The team also demonstrated that changing the activity of these neurons can alter behavior, prompting mice to eat even when they are full or feeling unwell. 

Building on these findings, the new research has detailed distinct groups of neurons in the same central region of the amygdala that respond specifically to thirst and others that respond to hunger, guided by a complex web of molecular cues.

“One of these groups of neurons is solely dedicated to regulating the desire to drink, the first ‘thirst neuron’ that has been identified in the amygdala,” explains Federica Fermani, who led the study. “When we activated these neurons, the mice drank more, and when we suppressed their activity, the mice drank less. We also identified another group of neurons in the same region of the amygdala that drives thirst but also plays a role in regulating hunger. These findings highlight how some neurons show remarkable specialization for specific behaviors, while others have more general roles in guiding food and drink choices.”

To explore how neurons in the central nucleus of the amygdala regulate drinking and eating, the researchers used advanced genetic tools to study brain activity in mice during hunger, thirst, and when they were already full and hydrated. One method, called optogenetics, allowed the team to activate specific neurons using light-sensitive proteins and a laser precisely tuned to trigger those cells. They also used approaches to silence the neurons, observing how their absence influenced the mice’s tendency to eat or drink. By combining this with new methods that enable the monitoring of individual neurons across multiple brain regions, the researchers mapped where these neurons receive information and identified other brain regions they communicate with. 

Raising new questions

Mapping the pathways these neurons use to communicate with other brain regions revealed connections to areas involved in processing sensory information about food and water, such as the parabrachial complex. The study also explored how the brain balances other factors, such as taste, in shaping behavior. For example, by pairing a less-preferred drink flavor with targeted stimulation of neurons in the central amygdala, the researchers found they could change the mice’s choices, transforming a previously avoided flavor into a new favorite. Since the amygdala’s structure is similar in mice and humans, the researchers suggest these findings could improve our understanding of how emotions and motivations influence our own eating and drinking habits.

“Basic drives like thirst and hunger ensure we eat and drink at the right times, giving our bodies the hydration and nutrition needed to survive,” explains Rüdiger Klein, Director at the Max Planck Institute for Biological Intelligence. “But these same neural circuits can also contribute to overeating or undereating, depending on the signals they encounter in the brain. By uncovering these processes, we gain a better understanding of how the brain emotionally evaluates food and drink, learns to associate them with pleasure or aversion, and how neural development shapes both innate and learned behaviors.”

This work opens the door to new questions – such as how the brain balances appetite, thirst, and emotions; how we know when we’ve had too little or too much to eat and drink; how competing needs are managed simultaneously; and how these circuits are affected in conditions like obesity, anorexia, or alcohol addiction.

Federica Fermani, Simon Chang, Ylenia Mastrodicasa, Christian Peters, Louise Gaitanos, Pilar L. Alcala Morales, Charu Ramakrishnan, Karl Deisseroth & Rüdiger Klein. Food and water intake are regulated by distinct central amygdala circuits revealed using intersectional genetics. Nature Communications, online 29 March 2025. link

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For over 50 years, it has been known that in the cerebral cortex of many mammals, neurons with the same function are grouped into columns. Now, for the first time, researchers at the Max Planck Institute for Biological Intelligence have been able to demonstrate these structures in the visual cortex of mice: here, neurons that process stimuli from the same eye form clusters. This adds to our general understanding of the structural organization of the brain – and may help to solve the mystery of the columnsˈ function.

***

Motion, color, light and shadow: everything we see is the result of complex computations in our brain – or, more precisely, in the visual cortex. This is where stimuli that hit our retina are broken down into their individual components, processed and assembled into what we perceive. The neurons responsible for this process can each perform different tasks: for example, some mainly process motion, others lines or colors.

In the 1960s, David Hubel and Torsten Wiesel famously discovered that in the visual cortex, neurons with the same function are organized spatially in columns. This finding, along with their other discoveries about visual processing, was awarded the Nobel Prize in Physiology or Medicine in 1981. These so-called cortical columns have been considered elementary building blocks in the cerebral cortex of many mammals – including humans. However, such structures had not yet been detected in the visual cortex of many smaller animals, such as mice. As a result, cortical columns were thought to be reserved for mammals with more complex brains and particularly good eyesight.

A team led by Mark Hübener and Tobias Bonhoeffer has now shown for the first time that neurons are also arranged in columns in the visual cortex of mice. Using a technique called 2-photon microscopy, they discovered clusters of neurons that process visual information coming from the same eye. These clusters were most distinct in the middle layers of the visual cortex. However, the spatial proximity of cells processing input from the same eye continued in the overlying and underlying layers, thereby forming so-called ocular dominance columns.

Although the columnar organization of the cerebral cortex was described more than half a century ago, the function of these columns is still a matter of speculation. “A possible explanation for the cortical columns can be illustrated by where fans sit on the stands in a football stadium,” says Pieter Goltstein, the study`s first author. “If all the fans of one team are sitting together and cheering for their team at the same time, it is much more powerful than if the fans are spread out all over the stadium. It is possible that neurons with the same function can also work more efficiently when they are close together.”

The new study not only advances our general understanding of how the brain is organized. It also makes it possible to study the function of the cortical column in the mouse model organism – to perhaps ultimately answer the question what columns are good for.

Link

The post Neurons gather together for vision first appeared on Max Planck Neuroscience.

What happens in the body when we are hungry and see and smell food? A team of researchers at the Max Planck Institute for Metabolism Research has now been able to show in mice that adaptations in the liver mitochondria take place after only a few minutes. Stimulated by the activation of a group of nerve cells in the brain, the mitochondria of the liver cells change and prepare the liver for the adaptation of the sugar metabolism. The findings, published in the journal Science, could open up new avenues for the treatment of type 2 diabetes.

Hungry mice were presented with food that they could see and smell, but not eat. After just a few minutes, researchers analyzed the mitochondria in the liver and found that processes normally stimulated by food intake were activated.

Mitochondria in the liver get ready

The studies show that it is sufficient for the mice to see and smell food for a few minutes to influence the mitochondria in the liver cells. This is mediated by a previously uncharacterized phosphorylation in a mitochondrial protein. Phosphorylation is an important modification for the regulation of protein activity. The researchers also show that this phosphorylation affects the sensitivity of the liver to insulin. The researchers have thus discovered a new signalling pathway that regulates insulin sensitivity in the body.

Nerve cells in the hypothalamus

The effect on the liver is mediated by a group of nerve cells called POMC neurons. These neurons are activated within seconds by the sight and smell of food, signalling the liver to prepare for the incoming nutrients. The researchers also showed that the activation of POMC neurons alone is sufficient to adapt the mitochondria in the liver, even in the absence of food.

“When our senses detect food, our body prepares for food intake by producing saliva and digestive acid. We knew from previous studies that the liver also prepares for food intake. Now we have taken a closer look at the mitochondria in liver cells, because they are essential cell organelles for metabolism and energy production, and realised how surprisingly fast this adaptation takes place,” explains Sinika Henschke, first author of the study.

Jens Brüning, head of the study and director at the Max Planck Institute for Metabolism Research: “Our study shows how closely the sensory perception of food, adaptive processes in the mitochondria and insulin sensitivity are linked. Understanding these mechanisms is also important because insulin sensitivity is impaired in type 2 diabetes mellitus”.

Sinika Henschke, Hendrik Nolte, Judith Magoley, Tatjana Kleele, Claus Brandt, Christine Hausen, Claudia M. Wunderlich, Corinna A. Bauder, Philipp Aschauer, Suliana Manley, Thomas Langer, F. Thomas Wunderlich, Jens C. Brüning
Food perception promotes phosphorylation of MFFS131 and mitochondrial fragmentation in liver. Science, 26. April 2024 Link

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Animals possess specialized networks of neurons in the brain that receive signals about the outside world from the retina and respond by initiating appropriate behavior. Researchers at the Max Planck Institute for Biological Intelligence studied a genetic mutation in zebrafish that eliminates all connections between retina and brain throughout development. The team found that in these ‘deep-blind’ fish the brain circuits are fully functional, as direct brain stimulation with optogenetics can drive normal visual behavior. This shows that the assembly of the brain in zebrafish requires little, if any, visual experience.

***

Zebrafish, just like humans, rely heavily on vision: large parts of the brain are dedicated to processing visual information, and vision is crucial for the animal to find food and navigate its environment. Just like human babies, young zebrafish also learn from experience: They prefer familiar food and memorize where they found it. Underlying this process is the formation of new connections between brain cells and the refinement of old ones.

“When we study brain development, we broadly distinguish between innate and experience-dependent processes,” explains Herwig Baier, director at the Max Planck Institute for Biological Intelligence. “The assembly of neuronal circuits, for example in visual brain areas, is classically considered an experience-dependent process: the neuronal networks are thought to be shaped by visual inputs and neuronal activity.” But what happens if the visual information is never there in the first place?

To address this question, researchers have investigated how animals like fish or mice develop when they grow up in the dark. In this case, the brain is deprived of visual experience – but the eyes still send many signals to the brain. The retina normally converts patterns of photons that hit the back of the eye to patterns of electrical impulses, which are then transmitted to the brain by specialized cells with long axons called retinal ganglion cells. Retinal ganglion cells are the gatekeepers for the visual input that reaches the brain. Their activity pattern contains all the information that animals have about their visual surroundings. But this is not the only way in which the eye can talk to the brain.

During development, the retinal ganglion cells also generate their own neuronal activity. Sometimes, waves of electrical activity sweep across the retina’s entire surface, reach the central brain areas, and fine-tune the synaptic connections. In addition, the axons of retinal ganglion cells secrete molecular factors that are received by cells in the central brain and induce developmental changes. All these signals could potentially shape the circuitry of the brain. However, previous studies only looked at the effects of these factors in isolation and analyzed, for instance, how blindness affects brain development.

“To really understand how brain development depends on stimulation from the eyes, one needs to look at what happens when retinal ganglion cells are taken out of the equation,” says Shachar Sherman, lead author of a new study that investigated just this. To do so, the former graduate student in Herwig Baier’s department and his colleagues studied a zebrafish mutant known as lakritz. These mutants have a genetic defect that prevents retinal ganglion cells from forming. Importantly, the defects are restricted to the eye. If it weren’t for their dark color – “Lakritz” is the German word for licorice – one wouldn’t be able to tell the difference between mutants and their wildtype siblings.

Herwig Baier explains: “The lakritz mutant is not just blind; it is deep-blind. Its brain is entirely disconnected from the visual world and any retina-derived signals. This unique situation opened up the possibility to study the influence of retinal ganglion cells on brain development and behavior in a systematic and comprehensive fashion.”

The researchers raised young lakritz zebrafish and compared their brain development to zebrafish without the genetic defect. A virtual cell atlas of the zebrafish brain, developed in the department, helped to identify individual cells and to track their development. “To our surprise, we didn’t see much of a difference,” says Shachar Sherman. “In lakritz, all types of neuronal cells formed at the right place and numbers, only the speed of differentiation was slightly off.”

 

When zebrafish detect prey, their eyes send the information via retinal ganglion cells (black) to specialized brain networks. These networks activate muscles that move the zebrafish tail, causing the animal to turn towards the prey. In the lakritz mutant (bottom), retinal ganglion cells are missing. However, using laser light (blue arrow) and a zebrafish with genetically modified cells*, the researchers could activate the visual networks in the brain, which then elicited the same tail movements. The experiment confirmed that functional cell networks develop in the visual brain areas of young zebrafish even without any connections to the eyes.
* Marked here with a light green circle and labeled ChR2 for the expression of a protein called channelrhodopsin-2.
© Max Planck Institute for Biological Intelligence / Herwig Baier, Julia Kuhl

Given that the brains of lakritz zebrafish developed relatively normally, the researchers wanted to know if the fish are still able to perform behaviors usually triggered by vision. They looked at two such behaviors: orientation towards prey and so-called optokinetic eye movements, which are normally used to stabilize an image of the outside world.

“Since lakritz cannot see, they normally will never perform these behaviors, but the brain circuits might still be there waiting to act,” says Shachar Sherman. To test this, the team used optogenetics to directly activate the brain neurons that would normally become active when needed. Optogenetics is a technique that allows neuroscientists to introduce ‘light switches’ into the neurons of living brains. This way they can remotely control neuronal activity, provided they find ways to stimulate the neurons from the outside with light, a task made easy in zebrafish due to their small size and transparency. “Strikingly, lakritz reacted to the artificial stimuli as if they had actually seen a prey object,” recalls Shachar Sherman. “This shows us that the brain circuits required for these actions develop and function properly even when there is no input from the eyes at all.”

Taken together, the latest research from the Baier department shows that brain development is hardwired to a greater extent than previously thought. “Shachar’s work shows that a complex part of the vertebrate brain, with many dozens of cell types, can develop just fine without sensory inputs,” says Herwig Baier. “This highlights the power of genetically programmed algorithms in building the brain. If this works in zebrafish, why not also in larger animals?”

Future studies will tell how strongly the development of sensory systems across the animal kingdom depends on input from the outside; the eyes and visual brain areas are just one example. The more we know about these processes, the closer we will get to answering the philosophical question of ‘what’s nature and what’s nurture?’ – or, in other words, how much of our brain wiring is innate and how much of it depends on our biography. For now, at least in the zebrafish visual system, nature appears to be the winner.

Shachar Sherman, Irene Arnold-Ammer, Martin W. Schneider, Koichi Kawakami, Herwig BaierRetina-derived signals control pace of neurogenesis in visual brain areas but not circuit assembly Nature Communications, online 27 September 2023. Link

***

CONTACT:

Prof. Dr. Herwig Baier
Director
Max Planck Institute for Biological Intelligence
Martinsried
herwig.baier@bi.mpg.de

The post Vision in the brain – hardwired for action first appeared on Max Planck Neuroscience.

An orchestra of complex neuronal networks performs a symphonic masterpiece called vision – an exciting field for neurobiologists like Alexander Borst, director at the Max Planck Institute for Biological Intelligence. In his department’s latest study, the scientists found a microcircuit which inverts excitatory to inhibitory signals and is thus able to transform a single type of neuronal input for multiple purposes. The discovery of this microcircuit is an important puzzle piece for the better understanding of the visual process of the fruit flies Drosophila and ultimately of vision itself.

***

Vision is one of the most important senses in humans. Accordingly, a large part of the brain is dedicated to processing visual information. In order to compute visual information quickly and accurately, a multitude of neuronal networks must perform a complex interplay – which fruit flies can help us to understand. Surprisingly, besides the obvious differences between the eyes of humans and fruit flies, many parallels can be found in the way how their brains process visual information. Since the visual system of flies is very efficient but significantly less complex than ours, it’s not surprising that this is one of the best understood neuronal networks in neuroscience.

In the flies’ visual system, a cascade of cells is responsible to transform light information into direction-specific signals. T4 cells, for example, respond to moving bright edges (ON-pathway), while T5 cells only respond to moving dark edges (OFF-pathway). Both, T4 and T5 cells have four subtypes that are tuned to the four cardinal directions (front-to-back, back-to-front, upwards and downwards). This means that each neuron only reacts to a specific direction of visual motion, their so-called preferred direction, while showing little reaction when stimulated by a moving edge in other directions (= null direction).

The mechanism to calculate direction selectivity in the ON-pathway has recently been deciphered by the department, leaving the exact implementation in the OFF-pathway yet to be understood. To this end, the scientists from Alexander Borst’s department developed a unique combination of calcium imaging with thermogenetic, optogenetic, and pharmacologic techniques to investigate the neuronal network underlying the OFF-pathway of Drosophila.

They found that several input neurons activate T5 cells when a signal moving in T5’s preferred direction is received. By suppressing or activating these input neurons, the scientists tested their role on how T5 cells compute direction. Taking together all the experiments, the team was able to confirm that the input neurons influence and shape the tuning of the T5 cells’ preferred direction.

In addition to activating input neurons, there are also inhibitory neurons, which reduce the outgoing signals of another cell. This is how all signals from directions other than the preferred direction is suppressed in T4 cells. Surprisingly, there are no such inhibitory neurons for T5 cells. This posed a mystery to the researchers: How does null direction suppression work in T5? In other words, how are these neurons able to react only to signals in their preferred direction without the inhibitory neurons?

The team led by Amalia Braun discovered a microcircuit underlying the T5 null direction suppression: CT1, an unusual large-field neuron, receives and inverses excitatory inputs, which leads to an inhibitory signal needed for null direction suppression. “By using genetic methods to remove single cell types, we could show that the tuning curve of a T5 cell’s direction detection substantially broadened when CT1 is gone. This could also be confirmed by using algorithmic modeling,” explains Amalia Braun. “Thus, while the excitatory neurons influence T5 cells directly for their preferred direction, an excitatory signal taking the detour via a CT1 cell inverting the signal leads to null direction suppression.”

With the discovery of this microcircuit, the department could once again add a new act to the complex symphonic composition of Drosophila’s visual system. “The CT1 microcircuit is a striking example for the multilayered and diverse mechanisms of inhibition and excitation in the brain, and how a neuronal network leverages a single type of signal for multiple purposes”, summarizes last author Matthias Meier.

The identification of this microcircuit, enabling and shaping motion detection, is substantially deepening our understanding of the visual processing of Drosophila – and ultimately of vision itself.

Amalia Braun, Alexander Borst, Matthias Meier. Disynaptic inhibition shapes tuning of OFF motion detectors in Drosophila. Current Biology, online 25 May 2023. Link

CONTACT:
Prof. Dr. Alexander Borst
Director
Max Planck Institute for Biological Intelligence
Martinsried
E-Mail: alexander.borst@bi.mpg.de

The post Fruit fly’s complex symphony of vision first appeared on Max Planck Neuroscience.

Knowing when it’s time for a meal – and when to stop eating again – is important to survive and to stay healthy for humans and animals alike. Researchers at the Max Planck Institute for Biological Intelligence investigated how the brain regulates feeding behavior in mice. The team found that the hormone ghrelin activates specialized nerve cells in a brain region known as the amygdala. Here, the interaction between ghrelin and the specialized neurons promotes food consumption and conveys hunger and the pleasant and rewarding feelings associated with eating.

***

Hunger is a powerful sensation with important biological underpinnings. It signals the body to look for food, which is a crucial behavior to prevent starvation and ensure survival. When we’re hungry, we crave food – and when we finally get to eat, our body rewards us with pleasant feelings and a general state of happiness.

A network of brain circuits and signaling pathways orchestrates the eating behavior of humans and animals and elicits the associated sensations. One of the central players in this network is the hormone ghrelin. It is released by stomach cells when humans and animals are hungry or fasting, and promotes feeding behavior.

The department of Rüdiger Klein at the Max Planck Institute for Biological Intelligence studies the brain networks that underly feeding behavior in mice. To this end, the researchers conducted a thorough analysis of the different cell types in a brain region known as the central amygdala. “Previously, the amygdala had mostly been studied in the context of feelings like fear and reward, while the regulation of feeding was thought to happen in different parts of the brain, such as the hypothalamus,” says Christian Peters, a postdoctoral researcher in the department.

Peters and his colleagues analyzed individual cells in the central amygdala, studying messenger RNA molecules – the cell’s working copies of their genes. The analysis revealed that the cells are organized into nine different cell clusters. Some of these clusters promote appetite while others inhibit it, and they adjust their production of messenger RNAs when the mice are fed or fasting.

“We now have a much better understanding of the diversity of cell types and the physiological processes that promote feeding in the central amygdala,” says Rüdiger Klein. “Our research uncovers for the first time that the ‘hunger hormone’ ghrelin also acts on cells in the central amygdala.” There, it activates a small subset of cell clusters, collectively marked by the presence of the protein Htr2a, to increase feeding.

The scientists found that the Htr2a neurons became active after an overnight fast or when stimulated by the hormone ghrelin. The cells also responded when the researchers presented food to the mice. “We think that ghrelin performs multiple functions,” explains Christian Peters. “When mice are hungry, ghrelin activates the appetitive brain regions to predispose the animals for eating. In addition, the hormone enhances the activity in brain circuits, such as the amygdala, that confer rewards, which is likely an incentive to eat additional food.” This way, ghrelin increases the palatability of food in proportion to how satiated the mice currently are.

After a fasting diet, when the animals were very hungry the activity of Htr2a neurons was not needed to start feeding, presumably because the tastiness of food is less important under these conditions. “Other brain circuits, for example the hypothalamus, which regulate the body’s metabolism, take over and signal the mice that it’s important to eat in order to survive,” says Christian Peters.

Feeling hungry or satiated has profound impacts on physical but also on emotional wellbeing, as probably everyone knows by the pleasures associated with eating tasty food. “The neuronal networks that convey these feelings are obviously linked to those that control eating, yet it is not fully understood how exactly they influence each other,” says Rüdiger Klein.

“If we figure out these connections, we will better understand the neuronal processes that are involved in pathological eating behaviors, such as overeating,” concludes Christian Peters. “There are numerous biological factors that contribute to such a complex behavior and we have to look at the physiological processes to understand these factors.”

Ultimately, this knowledge might lead to novel therapeutic approaches to alleviate eating disorders. For now, the research lays the groundwork for further studies to investigate how specific neuron populations are involved in the neuronal circuits that control feeding. It also adds another important piece to the puzzle of understanding how the brain orchestrates behavior.

Christian Peters, Songwei He, Federica Fermani, Hansol Lim, Wenyu Ding, Christian Mayer, Rüdiger Klein. Transcriptomics reveals amygdala neuron regulation by fasting and ghrelin thereby promoting feeding. Science Advances, online 24 May 2023. Link

CONTACT:

Prof. Dr. Rüdiger Klein
Director
Max Planck Institute for Biological Intelligence
Martinsried
E-Mail: ruediger.klein@bi.mpg.de

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When one travels through rough terrain, maps come in handy. They also help researchers to study the complex organization of the brain. Scientists at the Max Planck Institute for Biological Intelligence have created a new set of maps for the zebrafish brain. They determined the activity of hundreds of genes with single-cell resolution and assembled the maps into an interactive atlas. The online resource supports researchers in finding their way around the brain of this vertebrate and provides new insights into neural structure and function.

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An intricate network of brain cells (neurons) enables zebrafish to sense their environment, find food or mating partners and escape predators. All of these cells harbor the same genetic information, yet they specialize in different functions. It’s the expression of certain genes – the process of copying the genetic information into messenger RNAs and translating them into proteins – that determines a neuron’s shape, connectivity and role in behavior. Neurons with similar properties belong to the same type. It is estimated that there are hundreds, if not thousands, of different types in a fish brain. Similar numbers apply to the human brain.

Knowing which genes are expressed and where helps researchers to understand how the brain functions and how it controls zebrafish behavior. However, the neuronal cell types that underly a specific behavior are notoriously difficult to unravel, and the maps that help scientists find their way around the brain have many blank spots.

“We previously had only limited information on gene expression in the zebrafish brain,” explains Inbal Shainer, a postdoctoral researcher in Herwig Baier’s department. “The data was low in resolution and could not be combined with the latest cell type and brain structure maps. Our work now fills this gap.”

To reduce the blank spots in existing maps, Inbal Shainer, Enrico Kuehn and their colleagues used a method that makes the expression of individual genes visible under the microscope. The method is sensitive enough to detect differences in gene expression across the entire zebrafish brain at very high resolution – down to the level of single cells.

From the obtained data, the researchers prepared an expression map for each gene and merged hundreds of these maps into an atlas. The new gene expression atlas integrates seamlessly with the existing data of the Max Planck Zebrafish Brain (mapzebrain) atlas, which contains information on brain structures, cell types, and the connections between cells. By looking at these features and the gene expression combined, scientists can get a more holistic picture of how information is processed in the zebrafish brain.

For example, the researchers studied how environmental stimuli change the expression of the cfos gene – a marker for highly active nerve cells. When a young zebrafish took in food, the cfos gene expression increased in areas of the brain that detect prey and control hunting movements, but also in a group of cells that are connected to the lateral hypothalamus, a brain region involved in signaling hunger and satiety.

“Including the gene expression into mapzebrain has already provided us with exciting new insights. Follow-up experiments will show if the cells we found are indeed eliciting a satiety signal,” says Enrico Kuehn, molecular biologist in Herwig Baier’s department.

The zebrafish atlas is an open-source online tool, and the research community is constantly contributing data to the existing datasets. Scientists can inspect and analyze images online, download them to their devices, or connect the atlas with other online tools.

The researchers in Herwig Baier’s department are optimistic that the mapzebrain atlas will continue to grow, as more genes and more detailed maps of brain cells are being added. As a next step, the team aims to include information on neuronal circuits that was recently obtained by electron microscopy. “Combining different datasets allows the zebrafish research community to gain entirely new insights into the genetic basis of brain function. This will enable us to better understand how brains develop and how they operate,” concludes Inbal Shainer.

CONTACT:

Prof. Dr. Herwig Baier
Director
Max Planck Institute for Biological Intelligence
Martinsried
E-Mail: herwig.baier@bi.mpg.de

Inbal Shainer*, Enrico Kuehn*, Eva Laurell, Mariam Al Kassar, Nouwar Mokayes, Shachar Sherman, Johannes Larsch, Michael Kunst, Herwig Baier. A single-cell resolution gene expression atlas of the larval zebrafish brain. Science Advances, online 22 February 2023.  Link    * equal contribution

The post Mapping unknown territory first appeared on Max Planck Neuroscience.