Past and current research

Keep going or give up? Neural circuits underpinning goal-directed behavior

What drives behavioral persistence versus quitting?

We recently identified a neural circuit in the fly’s learning center that drives gradually increasing food odor tracking, which can be efficiently suppressed by extrinsic, but directly innervating, feeding-related neuromodulatory neurons. The relative activity of neurons in this circuit is regulated by the neurotransmitters dopamine and octopamine (the invertebrate counterpart to norepinephrine) counteracting each other in a state-dependent manner.

Are we victims of our senses?

Ilona gave a TEDx talk about her research. Check it out here: TEDxTUM

How Do Behavioral Context and Internal State Influence Sensory Perception and Behavior?

Ilona was interviewed by Latest Thinking to talk about her research.

Smelling and tasting what’s good

The taste neurons in the leg of the fruit fly are activated via two types of polyamine receptors. This helps the fly to choose food and good egg-laying sites.
© MPI of Neurobiology/L. Loschek

May 04, 2016

The amount and composition of nutrients required by the body vary according to its state and physiological circumstances. Polyamines, for example, are needed in greater quantities whenever tissues develop, grow or regenerate. Low polyamine levels are associated with neurodegenerative diseases, ageing and fertility decline. Excess polyamines, however, may play a role in the development of cancer. Together with colleagues from Sweden, scientists from the Max Planck Institute of Neurobiology in Martinsried have now identified the receptors enabling insects to recognize polyamines in food. The study suggests that the ability to identify polyamines via the senses of taste and smell could have influenced animal survival and reproduction.

Polyamines are small organic compounds that play a role in such fundamental cellular processes like cell division and growth. Consequently, polyamine deficiency can have negative impacts on health, cognition, fertility, reproduction and life expectancy. Since excessive polyamine concentrations can also be harmful, the supply of polyamines to the body should match its current requirements. Polyamines are particularly demanded during growth, injury or periods of increased physical demands, such as pregnancy. The body is able to produce some of the required polyamines by itself, and also with the help of intestinal bacteria. Still, a considerable amount of polyamines is obtained from food. High polyamine concentrations are found, for example, in oranges, ripe cheese, tea and some legumes. As the body’s own polyamine production decreases with age, the importance of obtaining them from food increases over time.

Some polyamines have characteristic names like cadaverine, spermine and putrescine (putridus in Latin means rotten or decayed). Hence, these substances have in higher concentrations an unpleasant smell and signal danger to humans and many animals. Yet they are essential for survival in small quantities. The role played by the odour and, possibly, the taste of polyamines when it comes to choosing beneficial food remains unclear. The same is true for the mechanism by which the molecules are recognized. “The sensory systems to detect odours and tastes are very similar between flies and humans,” explains Ilona Grunwald Kadow, Research Group Leader at the Max Planck Institute of Neurobiology. “We therefore used the fruit fly as a model system to study whether and how the animals perceive polyamines and what this means for them.” The neurobiologists succeeded in demonstrating that food rich in polyamines, for example overripe fruit, considerably increases the number and survival of fly offspring.

The researchers observed that flies are strongly attracted by the smell of polyamines. Female flies preferred to lay their eggs on older, polyamine-rich fruit rather than on fresher fruit. “The flies must be able to perceive the polyamines – but how?” Ashiq Hussain, one of the study’s two first authors, sums up the key question. The scientists discovered that the animals not only perceive the odour but also use their sense of taste to find and examine polyamine-rich sources of food. Under the microscope they observed which taste and olfactory cells became active when the flies perceived the polyamines. Combined with behavioural and genetic studies, they were then able to identify three receptors, with the help of which the chemosensory neurons are able to recognize the smell and taste of polyamines.

The results show that flies find a polyamine-rich food source first by its odour, using the receptors IR76b and IR41a. The taste neurons then evaluate the quality of the identified polyamines with the help of the IR76b receptor and a bitter receptor. As is the case in humans, an excessively high polyamine concentration appears to deter the flies. They only ate or laid their eggs on polyamine-rich food if the bitter taste of the polyamines was concealed by other food components, for example sugar. “A good mechanism for recognizing the optimal concentration of these substances,” explains Ashiq Hussain.

The three receptors that enable the recognition of polyamines belong to a class of proteins that is very old, in evolutionary terms. They are related to receptors that control synaptic activities of neurons. “It is therefore possible that the recognition of polyamines through these receptors improved the chances of survival of animals at an early stage in evolutionary history,” says Mo Zhang, co-first author of the study, summarizing the significance of the findings. “If animals were able to sense these important nutritional components, they could find and consume them in beneficial quantities.” The researchers plan to investigate whether mammals can evaluate polyamines in their food as well and thus tailor their consumption to their requirements.

SM/HR

Two receptors each in the smell and taste organs enable the fruit fly to track down vital polyamines in food.
© MPI of Neurobiology/Gompel

Pregnancy changes perception of odours and tastes

The reproductive state of the female fly sends signals to the brain, after which the sensory perception changes. The image shows part of the reproductive system with the uterus of the female fly.
© MPI of Neurobiology/ Friedrich

May 04, 2016

The perception and reactions to odours and tastes can change in pregnancy, sometimes dramatically. This is also true for flies. The mechanisms, however, that trigger these changes are not understood in either mammals or insects. Scientists from the Max Planck Institute of Neurobiology in Martinsried now succeeded in demonstrating that the concentration of a certain receptor increases in the sensory organs of gravid fruit fly females. As a result, the taste and odour of important nutrients, called polyamines, are processed differently in the brain: Pregnant flies favour nutrition that is rich in polyamines and increase their reproductive success in this way.

A pregnancy represents a huge challenge for the mother’s body. To provide optimal nutrition for the developing offspring, her nutrition must be adapted to the altered requirements. “We wanted to find out whether and how expectant mothers can sense the nutrients they need,” explains Ilona Grunwald Kadow, Research Group Leader at the Max Planck Institute of Neurobiology.

Polyamines are nutrients that can be produced by both the body itself and by intestinal bacteria. However, some of the polyamines needed must be obtained from food. With advancing age, the consumption of polyamines through food increases in importance, as the body’s own production declines. Polyamines play a role in numerous cell processes and a polyamine deficiency can have a negative impact on health, cognition, reproduction and life expectancy. An excess of polyamines can also be harmful, however. The intake of polyamines should therefore be adapted to the body’s current needs.

The Max Planck neurobiologists now succeeded in demonstrating that, after mating, female fruit flies show a preference for food with a high polyamine content. A combination of behavioural studies and physiological tests revealed that the change in the appeal of polyamines to flies before and after mating is triggered by a neuropeptide receptor known as the sex peptide receptor (SPR) and its neuropeptide binding partner. “It was already known that the SPR boosts egg production in mated flies,” explains Ashiq Hussain, one of the study’s two first authors. “But we were surprised to discover that the SPR also regulates the activity of the sensory neurons that recognize the taste and smell of polyamines.”

Considerably more SPR receptors are integrated into the surfaces of the chemosensory neurons in pregnant females. This increase in neuropeptide signalling modifies the reaction of the sensory neurons to the odour and taste. The thereby intensified odour and taste perception thus occurs at a very early stage in the nervous system. The importance of the receptor became clear when the researchers increased the presence of SPRs in the olfactory and taste neurons of virgin females, using a genetic tool: This change was sufficient to enable the neurons of the virgin flies to react more strongly to polyamines, which ultimately resulted in a change of their preference. Like their mated species counterparts, virgins now preferred the polyamine-rich food sources.

The study demonstrated, for the first time, the existence of a mechanism through which pregnancy modifies specific chemosensory neurons and alters the perception of important nutrients and behaviour towards them. “Because smell and taste are processed in a similar way in insects and mammals, a corresponding mechanism in humans could also ensure an optimal nutritional supply for the developing life,” presumes Habibe Üc̗punar, second first author of the study. In a concurrently published study, the scientists were also able to demonstrate how the important polyamines are actually sensed and evaluated by the fruit flies.

SM/HR

Decision-making in the fly brain

Nerve cells that use dopamine as a neurotransmitter (green) enable hungry flies to ignore danger signs and modulate their innate behaviour.
© MPI of Neurobiology/ Friedrich

August 20, 2015

For most of us, a freshly brewed cup of coffee smells wonderful. However, individual components that make up the fragrance of coffee can be extremely repulsive in isolation or in a different combination. The brain therefore relativizes and evaluates the individual components of a fragrance. Only then is an informed decision possible as to whether an odour and its source are “good” or “bad”. Scientists from the Max Planck Institute of Neurobiology in Martinsried have discovered how conflicting smells are processed in the mushroom body of the brain of the fruit fly. The results assign a new function to this brain region and show that sensory stimuli are evaluated in a situation-dependent context. In this way the insects are able to make an appropriate decision on the spur of the moment.

Most sensory impressions are complex. For example, a fragrant substance usually appears in combination with many other odours - like the smell of the aforementioned cup of coffee, which consists of over 800 individual odours, including some unpleasant ones. For the fruit fly Drosophila, the smell of carbon dioxide (CO2) is repellent. Among other things, the gas is released by stressed flies to warn other members of the species. When the insects smell CO2 an innate flight response is triggered. However, CO2 is also produced by overripe fruit – a coveted source of food for many insects. Foraging flies must therefore be able to ignore their innate aversion to CO2 in instances where the gas is present in combination with food odours. It is still poorly understood how the brain compares individual olfactory sensations and classifies them according to the situation at hand in order to reach a sensible decision (here: food or danger).

“The opposing significance of CO2 for fruit flies is an ideal starting point to explore how the brain correctly evaluates individual sensory impressions depending on the situation,” says Ilona Grunwald Kadow. Together with her team at the Max Planck Institute of Neurobiology, she studies how the brain processes odours and makes decisions based on the results. The scientists have now been able to show that complex or opposing sensory information is processed in the mushroom body. Until now, this brain area was thought to be a centre for learning and memory storage. The new results show that the mushroom body has an additional function: it evaluates sensory impressions independently of learned content and memory to allow instantaneous decisions.

The scientists were able to show that CO2 activates neurons in the neural network that includes the mushroom body. Those neurons, in turn, trigger the flies’ flight behaviour. However, if CO2 occurs along with food odours, the food odour stimulates neurons within the mushroom body network that release the neurotransmitter dopamine. Dopamine occurs in many species, including humans, in connection with positive values. When food smells are present along with CO2, these dopaminergic neurons in fruit flies transmit this information to the mushroom body, where they suppress the innate CO2 response by inhibiting “avoidance neurons”.

“Interestingly, the experience that CO2 frequently occurs together with food odours does not cause the insects to lose their aversion to CO2 forever,” says Grunwald Kadow. When the information about the simultaneous occurrence of CO2 and food odours is transmitted to the “learning centre” in the mushroom body, an immediate change of behaviour occurs, but not a permanent change with regard to the negative evaluation of CO2. This could apply to other sensory impressions as well, such as vision. The researchers speculate that the absence of a permanent change in behaviour could be vital in many situations. The smell of predators, for example, triggers an instinctive fear in humans. We do not lose this fear, even after experiencing caged predators and their smell at a zoo. The human brain therefore also appears to compare and draw different conclusions depending on the circumstances.

SM/HR

Hunger affects decision making and perception of risk

This projection neuron forwards carbon dioxide information to the region in the fly's brain where the animals can gauge internal and external signals.
© MPI for Neurobiology / Purayil & Kadow

June 25, 2013

Hungry people are often difficult to deal with. A good meal can affect more than our mood, it can also influence our willingness to take risks. This phenomenon is also apparent across a very diverse range of species in the animal kingdom. Experiments conducted on the fruit fly, Drosophila, by scientists at the Max Planck Institute of Neurobiology in Martinsried have shown that hunger not only modifies behaviour, but also changes pathways in the brain.

Animal behaviour is radically affected by the availability and amount of food. Studies prove that the willingness of many animals to take risks increases or declines depending on whether the animal is hungry or full. For example, a predator only hunts more dangerous prey when it is close to starvation. This behaviour has also been documented in humans in recent years: one study showed that hungry subjects took significantly more financial risks than their sated colleagues.

Also the fruit fly, Drosophila, changes its behaviour depending on its nutritional state. The animals usually perceive even low quantities of carbon dioxide to be a sign of danger and opt to take flight. However, rotting fruit and plants – the flies’ main sources of food – also release carbon dioxide. Neurobiologists in Martinsried have now discovered how the brain deals with this constant conflict in deciding between a hazardous substance and a potential food source taking advantage of the fly as a great genetic model organism for circuit neuroscience.

In various experiments, the scientists presented the flies with environments containing carbon dioxide or a mix of carbon dioxide and the smell of food. It emerged that hungry flies overcame their aversion to carbon dioxide significantly faster than fed flies – if there was a smell of food in the environment at the same time. Facing the prospect of food, hungry animals are therefore significantly more willing to take risks than sated flies. But how does the brain manage to decide between these options?

Avoiding carbon dioxide is an innate behaviour and should therefore be generated outside the mushroom body in the fly’s brain: previously, the nerve cells in the mushroom body were linked only with learning and behaviour patterns that are based on learned associations. However, when the scientists temporarily disabled these nerve cells, hungry flies no longer showed any reaction whatsoever to carbon dioxide. The behaviour of fed flies, on the other hand, remained the same: they avoided the carbon dioxide.

In further studies, the researchers identified a projection neuron which transports the carbon dioxide information to the mushroom body. This nerve cell is crucial in triggering a flight response in hungry, but not in fed animals. “In fed flies, nerve cells outside the mushroom body are enough for flies to flee from the carbon dioxide. In hungry animals, however, the nerve cells are in the mushroom body and the projection neuron, which carries the carbon dioxide information there, is essential for the flight response. If mushroom body or projection neuron activity is blocked, only hungry flies are no longer concerned about the carbon dioxide,” explains Ilona Grunwald-Kadow, who headed the study.

The results show that the innate flight response to carbon dioxide in fruit flies is controlled by two parallel neural circuits, depending on how satiated the animals are. “If the fly is hungry, it will no longer rely on the ‘direct line’ but will use brain centres to gauge internal and external signals and reach a balanced decision,” explains Grunwald-Kadow. “It is fascinating to see the extent to which metabolic processes and hunger affect the processing systems in the brain,” she adds.

SM/HR