David Tadres

All Publications

• An essential experimental control for functional connectivity mapping with optogenetics GENETICS Tadres, D., Shiozaki, H. M., Tastekin, I., Stern, D. L., Louis, M. 2025

  Abstract

  To establish functional connectivity between two candidate neurons that might form a circuit element, a common approach is to activate an optogenetic tool such as Chrimson in the candidate pre-synaptic neuron and monitor fluorescence of the calcium-sensitive indicator GCaMP in a candidate post-synaptic neuron. While performing such experiments in Drosophila, we found that low levels of leaky Chrimson expression can lead to strong artifactual GCaMP signals in presumptive postsynaptic neurons even when Chrimson is not intentionally expressed in any particular neurons. Withholding all-trans retinal, the chromophore required as a co-factor for Chrimson response to light, eliminates GCaMP signal but does not provide an experimental control for leaky Chrimson expression. Leaky Chrimson expression appears to be an inherent feature of current Chrimson transgenes, since artifactual connectivity was detected with Chrimson transgenes integrated into multiple genomic locations. While these false-positive signals may complicate the interpretation of functional connectivity experiments, we illustrate how a no-Gal4 negative control improves interpretability of functional connectivity assays. We also propose a simple but effective procedure to identify experimental conditions that minimize potentially incorrect interpretations caused by leaky Chrimson expression.

  View details for DOI 10.1093/genetics/iyaf174

  View details for Web of Science ID 001586213500001

  View details for PubMedID 40845144

• Odorant Receptors Mediating Avoidance of Toxic Mustard Oils in Drosophila melanogaster Are Expanded in Herbivorous Relatives MOLECULAR BIOLOGY AND EVOLUTION Matsunaga, T., Reisenman, C. E., Goldman-Huertas, B., Rajshekar, S., Suzuki, H. C., Tadres, D., Wong, J., Louis, M., Ramirez, S. R., Whiteman, N. K. 2025; 42 (9)

  Abstract

  Plants release defense volatile compounds that can deter herbivores. Among them are electrophilic toxins, such as isothiocyanates from mustard plants, that activate pain receptors by contact (i.e. taste) in many animals, including Drosophila melanogaster. While specialist insects have evolved strategies to tolerate toxicity and use mustard plants as hosts, it is unclear whether nonspecialist insects detect and avoid electrophilic toxins via olfaction. To address this, and to understand if specialized insects co-opted these toxic compounds as host plant olfactory cues, we leveraged closely related drosophilid species, including the microbe-feeding D. melanogaster and Scaptomyza pallida, and the mustard-feeding specialist Scaptomyza flava. In olfactory assays, D. melanogaster exposed to allyl isothiocyanate volatiles were rapidly immobilized, demonstrating the high toxicity of this wasabi-derived compound to nonspecialists. Through single sensillum electrophysiological recordings from olfactory organs and behavioral assays, we identified an olfactory receptor (Or) necessary for volatile detection and behavioral aversion to allyl isothiocyanate in D. melanogaster. RNA-sequencing and heterologous expression revealed that S. flava possess lineage-specific, triplicated homologs of this Or and that each paralog exhibited broadened and distinct sensitivity to isothiocyanate compounds. Using AlphaFold2 modeling, site-directed mutagenesis, and electrophysiological recordings, we identified two critical amino acid substitutions that changed the sensitivity of these paralogs from fruit-derived odors to isothiocyanates in the mustard specialist S. flava. Our findings show that nonspecialists can detect electrophiles via olfaction and that their olfactory systems can rapidly adapt to toxic host plant niches through co-option and duplication of ancestral chemosensory genes with few amino acid changes.

  View details for DOI 10.1093/molbev/msaf164

  View details for Web of Science ID 001574589400001

  View details for PubMedID 40614170

  View details for PubMedCentralID PMC12448936

• Sensation of electric fields in the Drosophila melanogaster larva CURRENT BIOLOGY Tadres, D., Riedl, J., Eden, A., Bontempo, A. E., Lin, J., Reid, S. F., Roehrich, B., Williams, K., Sepunaru, L., Louis, M. 2025; 35 (8): 1848-1860.e4

  Abstract

  Electrosensation has emerged as a crucial sensory modality for social communication, foraging, and predation across the animal kingdom. However, its presence and functional role as well as the neural basis of electric field perception in Drosophila and other invertebrates remain unclear. In environments with controlled electric fields, we identified electrosensation as a new sense in the Drosophila melanogaster larva. We found that the Drosophila larva performs robust electrotaxis: when exposed to a uniform electric field, larvae migrate toward the cathode (negatively charged elecrode) and quickly respond to changes in the orientation of the field to maintain cathodal movement. Through a behavioral screen, we identified a subset of sensory neurons located at the tip of the larval head that are necessary for electrotaxis. Calcium imaging revealed that a pair of Gr66a-positive sensory neurons (one on each side of the head) encodes the strength and orientation of the electric field. Our results indicate that electric fields elicit robust behavioral and neural responses in the Drosophila larva, providing new evidence for the significance of electrosensation in invertebrates.

  View details for DOI 10.1016/j.cub.2025.03.014

  View details for Web of Science ID 001477624400001

  View details for PubMedID 40174584

  View details for PubMedCentralID PMC12040295

• Using the Raspberry Pi Virtual Reality (PiVR) System to StudyDrosophilaLarval Chemotaxis with Real and Virtual Odor Gradients. Cold Spring Harbor protocols Tadres, D., Saxena, N., Louis, M. 2024; 2024 (7)

  Abstract

  Here, we present a detailed protocol for the study of the orientation behavior of larvae of the fruit fly Drosophila melanogaster in response to both real and virtual odors (chemotaxis). An element common to the study of navigation directed by all sensory modalities is the need to correlate changes in behavioral states (e.g., crawling and turning) with temporal changes in the stimulus preceding these events. It has been shown recently that virtual odor landscapes, with any arbitrary geometry, can be created by combining a platform known as "Raspberry Pi virtual reality" (PiVR) with optogenetics. This methodology offers a technical foundation with which to characterize how the larval nervous system responds to stimulation by real and virtual odors. Furthermore, the experimental steps presented and discussed herein highlight important considerations that are needed to ensure experimental reproducibility. Finally, we believe that this framework can be easily adapted and generalized to allow investigators to study other sensory modalities in the Drosophila larva and in other animals.

  View details for DOI 10.1101/pdb.prot108120

  View details for PubMedID 37258057

• Tracking the Navigation Behavior ofDrosophilaLarvae in Real and Virtual Odor Gradients by Using the Raspberry Pi Virtual Reality (PiVR) System. Cold Spring Harbor protocols Tadres, D., Saxena, N., Louis, M. 2024; 2024 (7)

  Abstract

  In a closed-loop experimental paradigm, an animal experiences a modulation of its sensory input as a function of its own behavior. Tools enabling closed-loop experiments are crucial for delineating causal relationships between the activity of genetically labeled neurons and specific behavioral responses. We have recently developed an experimental platform known as "Raspberry Pi Virtual Reality" (PiVR) that is used to perform closed-loop optogenetic stimulation of neurons in unrestrained animals. PiVR is a system that operates at high temporal resolution (>30-Hz) and with low latencies. Larvae of the fruit fly Drosophila melanogaster are ideal to study the role of individual neurons in modulating behavior to aid the understanding of the neural pathways underlying various guided behaviors. Here, we introduce larval chemotaxis as an example of a navigational behavior in which an animal seeks to locate a target-in this case, the attractive source of an odor-by tracking a concentration gradient. The methodologies that we describe here combine the use of PiVR with the study of larval chemotaxis in real and virtual odor gradients, but these can also be readily adapted to other sensory modalities.

  View details for DOI 10.1101/pdb.top108098

  View details for PubMedID 37258056

• Depolarization block in olfactory sensory neurons expands the dimensionality of odor encoding SCIENCE ADVANCES Tadres, D., Wong, P. H., To, T., Moehlis, J., Louis, M. 2022; 8 (50): eade7209

  Abstract

  Upon strong and prolonged excitation, neurons can undergo a silent state called depolarization block that is often associated with disorders such as epileptic seizures. Here, we show that neurons in the peripheral olfactory system undergo depolarization block as part of their normal physiological function. Typically, olfactory sensory neurons enter depolarization block at odor concentrations three orders of magnitude above their detection threshold, thereby defining receptive fields over concentration bands. The silencing of high-affinity olfactory sensory neurons produces sparser peripheral odor representations at high-odor concentrations, which might facilitate perceptual discrimination. Using a conductance-based model of the olfactory transduction cascade paired with spike generation, we provide numerical and experimental evidence that depolarization block arises from the slow inactivation of sodium channels-a process that could affect a variety of sensory neurons. The existence of ethologically relevant depolarization block in olfactory sensory neurons creates an additional dimension that expands the peripheral encoding of odors.

  View details for DOI 10.1126/sciadv.ade7209

  View details for Web of Science ID 000905194200019

  View details for PubMedID 36525486

  View details for PubMedCentralID PMC9757753

• PiVR: An affordable and versatile closed-loop platform to study unrestrained sensorimotor behavior. PLoS biology Tadres, D., Louis, M. 2020; 18 (7): e3000712

  Abstract

  Tools enabling closed-loop experiments are crucial to delineate causal relationships between the activity of genetically labeled neurons and specific behaviors. We developed the Raspberry Pi Virtual Reality (PiVR) system to conduct closed-loop optogenetic stimulation of neural functions in unrestrained animals. PiVR is an experimental platform that operates at high temporal resolution (70 Hz) with low latencies (<30 milliseconds), while being affordable (

  View details for DOI 10.1371/journal.pbio.3000712

  View details for PubMedID 32663220

  View details for PubMedCentralID PMC7360024