publications

2024

1. Evolution of Taste Processing Shifts Dietary Preference

   Enrico Bertolini, Daniel Münch, Justine Pascual, Noemi Sgammeglia, Carlos Ribeiro, and Thomas O. Auer

   bioRxiv, Oct 2024

   Abs DOI

   Food choice is an important driver of speciation and invasion of novel ecological niches. However, we know little about the mechanisms leading to changes in dietary preference. Here, we use the three closely-related species Drosophila sechellia, D. simulans and D. melanogaster to study taste circuit and food choice evolution. D. sechellia, a host specialist, feeds exclusively on a single fruit (Morinda citrifolia, noni) - the latter two are generalists living on various substrates. Using quantitative feeding assays, we recapitulate the preference for noni in D. sechellia and detect conserved sweet but altered bitter sensitivity via calcium imaging in peripheral taste neurons. Noni surprisingly activates bitter sensing neurons more strongly in D. sechellia due to a small deletion in one single gustatory receptor. Using volumetric calcium imaging in the ventral brain, we show that instead of peripheral physiology, species-specific processing of noni and sugar signals in sensorimotor circuits recapitulates differences in dietary preference. Our data support that peripheral receptor changes alone cannot explain altered food choice but rather modifications in how sensory information is transformed into feeding motor commands.

2. Lack of Single Amino Acids Transcriptionally Remodels Sensory Systems to Enhance the Intake of Protein and Microbiota

   Gili Ezra-Nevo, Sílvia F. Henriques, Daniel Münch, Ana Patrícia Francisco, Célia Baltazar, Ana Paula Elias, Bart Deplancke, and Carlos Ribeiro

   bioRxiv, Jul 2024

   Abs DOI

   Adequate intake of dietary essential amino acids (eAAs) is vital for protein synthesis and metabolism. Any single eAA deprivation is sufficient to increase protein intake in Drosophila melanogaster. How such nutritional “needs” are transformed into behavioral “wants” remains poorly understood. We derived transcriptomes from the heads of flies deprived of individual eAAs to identify mechanisms by which this is achieved. We found that, while specific eAA deprivations have unique effects on gene expression, a large set of changes are shared across deprivations. We show that Or92a upregulation upon eAA deprivation increases the exploitation of yeast, the main protein source of flies. Furthermore, Ir76a upregulation was crucial for feeding on Lactobacillus, a gut bacterium that ameliorates the fitness of eAA-deprived flies. Our work uncovers common and unique transcriptional changes induced by individual eAA deprivations in an animal and reveals novel mechanisms underlying the organism’s behavioral and physiological response to eAA challenges.

2023

1. A Neuronal Substrate for Translating Nutrient State and Resource Density Estimations into Foraging Decisions

   Dennis Goldschmidt, Ibrahim Tastekin, Daniel Münch, Jin-Yong Park, Hannah Haberkern, Lúcia Serra, Célia Baltazar, Vivek Jayaraman, and 2 more authors

   bioRxiv, Jul 2023

   Abs DOI

   Foraging animals must balance the costs of exploring their surroundings with the potential benefits of finding nutritional resources. Each time an animal encounters a food source it must decide whether to initiate feeding or continue searching for potentially better options. Experimental evidence and patch foraging models predict that this decision depends on both nutritional state and the density of available resources in the environment. How the brain integrates such internal and external states to adapt the so-called exploration-exploitation trade-off remains poorly understood. We use video-based tracking to show that Drosophila regulates the decision to engage with food patches based on nutritional state and travel time between food patches, the latter being a measure of food patch density in the environment. To uncover the neuronal basis of this decision process, we performed a neurogenetic silencing screen of more than 400 genetic driver lines with sparse expression patterns in the fly brain. We identified a population of neurons in the central complex that acts as a key regulator of the decision to engage with a food patch. We show that manipulating the activity of these neurons alters the probability to engage, that their activity is modulated by the protein state of the animal, and that silencing these neurons perturbs the ability of the animal to adjust foraging decisions to the fly’s travel time between food patches. Taken together, our results reveal a neuronal substrate that integrates nutritional state and patch density information to control a specific foraging decision, and therefore provide an important step towards a mechanistic explanation of the cognitive computations that resolve complex cost-benefit trade-offs.

2. Generating Parallel Representations of Position and Identity in the Olfactory System

   István Taisz, Erika Donà, Daniel Münch, Shanice N. Bailey, Billy J. Morris, Kimberly I. Meechan, Katie M. Stevens, Irene Varela-Martínez, and 5 more authors

   Cell, Jun 2023

   Abs DOI

   In Drosophila, a dedicated olfactory channel senses a male pheromone, cis-vaccenyl acetate (cVA), promoting female courtship while repelling males. Here, we show that separate cVA-processing streams extract qualitative and positional information. cVA sensory neurons respond to concentration differences in a 5-mm range around a male. Second-order projection neurons encode the angular position of a male by detecting inter-antennal differences in cVA concentration, which are amplified through contralateral inhibition. At the third circuit layer, we identify 47 cell types with diverse input-output connectivity. One population responds tonically to male flies, a second is tuned to olfactory looming, while a third integrates cVA and taste to coincidentally promote female mating. The separation of olfactory features resembles the mammalian what and where visual streams; together with multisensory integration, this enables behavioral responses appropriate to specific ethological contexts.

2022

1. The Neuronal Logic of How Internal States Control Food Choice

   Daniel Münch, Dennis Goldschmidt, and Carlos Ribeiro

   Nature, Jul 2022

   Abs DOI

   When deciding what to eat, animals evaluate sensory information about food quality alongside multiple ongoing internal states1–10. How internal states interact to alter sensorimotor processing and shape 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 find that metabolic state shapes sensorimotor processing across large sections of the neuropil. By contrast, reproductive state acts locally to define how sensory information is translated into feeding motor output. These two states thus 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 towards protein-rich food. We thus identify a generalizable principle by which distinct internal states are integrated to shape decision making and propose a strategy to uncover and functionally validate how internal states shape behaviour.

2020

1. Nutrient Homeostasis — Translating Internal States to Behavior

   Daniel Münch, Gili Ezra-Nevo, Ana Patrícia Francisco, Ibrahim Tastekin, and Carlos Ribeiro

   Current Opinion in Neurobiology, Feb 2020

   Abs DOI

   Behavioral neuroscience aims to describe a causal relationship between neuronal processes and behavior. Animals’ ever-changing physiological needs alter their internal states. Internal states then alter neuronal processes to adapt the behavior of the animal enabling it to meet its needs. Here, we describe nutrient-specific appetites as an attractive framework to study how internal states shape complex neuronal processes and resulting behavioral outcomes. Understanding how neurons detect nutrient states and how these are integrated at the level of neuronal circuits will provide a multilevel description of the mechanisms underlying complex feeding and foraging decisions.

2. TReND in Africa: Toward a Truly Global (Neuro)Science Community

   Tom Baden, Mahmoud Bukar Maina, Andre Maia Chagas, Yunusa Garba Mohammed, Thomas O. Auer, Ana Silbering, Lukas Tobel, Marie Pertin, and 12 more authors

   Neuron, Aug 2020

   DOI

2018

1. An Expression Atlas of Variant Ionotropic Glutamate Receptors Identifies a Molecular Basis of Carbonation Sensing

   Juan Antonio Sánchez-Alcañiz, Ana Florencia Silbering, Vincent Croset, Giovanna Zappia, Anantha Krishna Sivasubramaniam, Liliane Abuin, Saumya Yashmohini Sahai, Daniel Münch, and 8 more authors

   Nature Communications, Oct 2018

   Abs DOI

   Little is known about the role of variant ionotropic glutamate receptors (IRs) in insect taste. Here the authors characterise the expression pattern of IRs in the Drosophila gustatory system and highlight the role of one receptor, IR56d, in the detection of carbonation

2017

1. Take Time: Odor Coding Capacity across Sensory Neurons Increases over Time in Drosophila

   Daniel Münch and C. Giovanni Galizia

   Journal of Comparative Physiology A, Aug 2017

   Abs DOI

   Due to the highly efficient olfactory code, olfactory sensory systems are able to reliably encode enormous numbers of olfactory stimuli. The olfactory code consists of combinatorial activation patterns across sensory neurons, thus its capacity exceeds the number of involved classes of sensory neurons by a manifold. Activation patterns are not static but vary over time, caused by the temporally complex response dynamics of the individual sensory neuron responses. We systematically analyzed the temporal dynamics of olfactory sensory neuron responses to a diverse set of odorants. We find that response dynamics depend on the combination of sensory neuron and odorant and that information about odorant identity can be extracted from the time course of the response. We also show that new response dynamics can arise when mixing two odorants. Our data show that temporal dynamics of odorant responses are able to significantly enhance the coding capacity of olfactory sensory systems.

2. Minute Impurities Contribute Significantly to Olfactory Receptor Ligand Studies: Tales from Testing the Vibration Theory

   M. Paoli, D. Münch, A. Haase, E. Skoulakis, L. Turin, and C. G. Galizia

   eneuro, May 2017

   Abs DOI

   Several studies have attempted to test the vibrational hypothesis of odorant receptor activation in behavioral and physiological studies using deuterated compounds as odorants. The results have been mixed. Here, we attempted to test how deuterated compounds activate odorant receptors using calcium imaging of the fruit fly antennal lobe. We found specific activation of one area of the antennal lobe corresponding to inputs from a specific receptor. However, upon more detailed analysis, we discovered that an impurity of 0.0006% ethyl acetate in a chemical sample of benzaldehyde-d5 was entirely responsible for a sizable odorant-evoked response in Drosophila melanogaster olfactory receptor cells expressing dOr42b. Without gas chromatographic purification within the experimental setup, this impurity would have created a difference in the responses of deuterated and nondeuterated benzaldehyde, suggesting that dOr42b be a vibration sensitive receptor, which we show here not to be the case. Our results point to a broad problem in the literature on use of non-GC-pure compounds to test receptor selectivity, and we suggest how the limitations can be overcome in future studies.

2016

1. DoOR 2.0 - Comprehensive Mapping of Drosophila Melanogaster Odorant Responses

   Daniel Münch and C. Giovanni Galizia

   Scientific Reports, Feb 2016

   DOI
2. Ir40a Neurons Are Not DEET Detectors

   Ana F. Silbering, Rati Bell, Daniel Münch, Steeve Cruchet, Carolina Gomez-Diaz, Thomas Laudes, C. Giovanni Galizia, and Richard Benton

   Nature, Jun 2016

   Abs DOI

   ARISING FROM P. Kain et al. Nature 502, 507–512 (2013); doi:10.1038/nature12594 N,N-Diethyl-meta-toluamide (DEET) is the most widely used insect repellent, but it requires repeated application at high, potentially harmful, concentrations, which is prohibitively impractical and costly in the countries suffering most from insect vector-borne diseases; understanding DEET’s mode of action might…

3. The Circuitry of Olfactory Projection Neurons in the Brain of the Honeybee, Apis Mellifera

   Hanna Zwaka, Daniel Münch, Gisela Manz, Randolf Menzel, and Jürgen Rybak

   Frontiers in Neuroanatomy, Jun 2016

   Abs DOI

   In the honeybee brain, two prominent tracts - the medial and the lateral antennal lobe tract - project from the primary olfactory center, the antennal lobes, to the central brain, the mushroom bodies, and the protocerebral lobe. Intracellularly stained uniglomerular projection neurons (uPN) were reconstructed, registered to the 3D honeybee standard brain atlas, and then used to derive the spatial properties and quantitative morphology of the neurons of both tracts. We evaluated putative synaptic contacts of projection neurons using confocal microscopy. Analysis of the patterns of axon terminals revealed a domain-like innervation within the mushroom body lip neuropil. Projection neurons of the lateral tract arborized more sparsely within the lips and exhibited fewer synaptic boutons, while medial tract neurons occupied broader regions in the mushroom body calyces and the protocerebral lobe. Our data show that uPNs from the medial and lateral tract innervate both the core and the cortex of the ipsilateral mushroom body lip but differ in their innervation patterns in these regions. In the mushroombody neuropil collar we found evidence for ALT boutons suggesting the collar as a multi modal input site including olfactory input similar to lip and basal ring. In addition, our data support the conclusion drawn in previous studies that reciprocal synapses exist between projection neurons, octopaminergic-, and GABAergic cells in the mushroom body calyces. For the first time, we found evidence for connections between both tracts within the antennal lobe.

2014

1. More than Apples and Oranges - Detecting Cancer with a Fruit Fly’s Antenna

   Martin Strauch, Alja Lüdke, Daniel Münch, Thomas Laudes, C. Giovanni Galizia, Eugenio Martinelli, Luca Lavra, Roberto Paolesse, and 4 more authors

   Scientific Reports, Jan 2014

   Abs DOI

   Cancer cells and non-cancer cells differ in their metabolism and they emit distinct volatile compound profiles, allowing to recognise cancer cells by their scent. Insect odorant receptors are excellent chemosensors with high sensitivity and a broad receptive range unmatched by current gas sensors. We thus investigated the potential of utilising the fruit fly’s olfactory system to detect cancer cells. Using in vivo calcium imaging, we recorded an array of olfactory receptor neurons on the fruit fly’s antenna. We performed multidimensional analysis of antenna responses, finding that cell volatiles from different cell types lead to characteristic response vectors. The distances between these response vectors are conserved across flies and can be used to discriminate healthy mammary epithelial cells from different types of breast cancer cells. This may expand the repertoire of clinical diagnostics, and it is the first step towards electronic noses equipped with biological sensors, integrating artificial and biological olfaction.

2013

1. Weaker Ligands Can Dominate an Odor Blend Due to Syntopic Interactions.

   Daniel Münch, Benjamin Schmeichel, Ana F. Silbering, and C. Giovanni Galizia

   Chemical senses, Jan 2013

   Abs DOI

   Most odors in natural environments are mixtures of several compounds. Perceptually, these can blend into a new "perfume," or some components may dominate as elements of the mixture. In order to understand such mixture interactions, it is necessary to study the events at the olfactory periphery, down to the level of single-odorant receptor cells. Does a strong ligand present at a low concentration outweigh the effect of weak ligands present at high concentrations? We used the fruit fly receptor dOr22a and a banana-like odor mixture as a model system. We show that an intermediate ligand at an intermediate concentration alone elicits the neuron’s blend response, despite the presence of both weaker ligands at higher concentration, and of better ligands at lower concentration in the mixture. Because all of these components, when given alone, elicited significant responses, this reveals specific mixture processing already at the periphery. By measuring complete dose-response curves we show that these mixture effects can be fully explained by a model of syntopic interaction at a single-receptor binding site. Our data have important implications for how odor mixtures are processed in general, and what preprocessing occurs before the information reaches the brain.

2. The Looks of an Odour - Visualising Neural Odour Response Patterns in Real Time

   Martin Strauch, Clemens Müthing, Marc P. Broeg, Paul Szyszka, Daniel Münch, Thomas Laudes, Oliver Deussen, C. Giovanni Galizia, and 1 more author

   BMC Bioinformatics, Nov 2013

   Abs DOI

   Calcium imaging in insects reveals the neural response to odours, both at the receptor level on the antenna and in the antennal lobe, the first stage of olfactory information processing in the brain. Changes of intracellular calcium concentration in response to odour presentations can be observed by employing calcium-sensitive, fluorescent dyes. The response pattern across all recorded units is characteristic for the odour.

2010

1. Integrating Heterogeneous Odor Response Data into a Common Response Model: A DoOR to the Complete Olfactome.

   C. Giovanni Galizia, Daniel Münch, Martin Strauch, Anja Nissler, and Shouwen Ma

   Chemical senses, Oct 2010

   Abs DOI

   We have developed a new computational framework for merging odor response data sets from heterogeneous studies, creating a consensus metadatabase, the database of odor responses (DoOR). As a result, we obtained a functional atlas of all available odor responses in Drosophila melanogaster. Both the program and the data set are freely accessible and downloadable on the Internet (http://neuro.uni-konstanz.de/DoOR). The procedure can be adapted to other species, thus creating a family of "olfactomes" in the near future. Drosophila melanogaster was chosen because of all species this one is closest to having the complete olfactome characterized, with the highest number of deorphanized receptors available. The database guarantees long-term stability (by offering time-stamped, downloadable versions), up-to-date accuracy (by including new data sets as soon as they are published), and portability (for other species). We hope that this comprehensive repository of odor response profiles will be useful to the olfactory community and to computational neuroscientists alike.