David Owald

• Dr. rer. nat.
• PostDoc Position at Charité Universitätsmedizin Berlin

Romantic engagement can bias sensory perception. This ‘love blindness’ reflects a common behavioural principle across organisms: favouring pursuit of a coveted reward over potential risks¹. In the case of animal courtship, such sensory biases may support reproductive success but can also expose individuals to danger, such as predation2,3. However,...

Animal brains need to store information to construct a representation of their environment. Knowledge of what happened in the past allows both vertebrates and invertebrates to predict future outcomes by recalling previous experience. Although invertebrate and vertebrate brains share common principles at the molecular, cellular, and circuit-architec...

Romantic engagement can bias sensory perception. This 'love blindness' reflects a common behavioral principle across organisms: favoring pursuit of a coveted reward over potential risks. In the case of animal courtship, such sensory biases may support reproductive success but can also expose individuals to danger, such as predation. How do neural n...

Channelrhodopsins are light-gated ion channels used to control excitability of designated cells in large networks with high spatiotemporal resolution. While ChRs selective for H⁺, Na⁺, K⁺ and anions have been discovered or engineered, Ca²⁺-selective ChRs have not been reported to date. Here, we analyse ChRs and mutant derivatives with regard to the...

All animals constantly need to weigh their options based on new experiences: something initially considered bad can become better in the light of something worse. A new study now shows how flies re-evaluate between better and worse.

In vertebrates, several forms of memory-relevant synaptic plasticity involve postsynaptic rearrangements of glutamate receptors. In contrast, previous work indicates that Drosophila and other invertebrates store memories using presynaptic plasticity of cholinergic synapses. Here, we provide evidence for postsynaptic plasticity at cholinergic output...

Quiescent states such as sleep restore vital physiological functions across phyla and are characterized by reduced locomotion and diminished behavioral responsiveness to external stimuli. In humans, synchronous activity across cortical networks is a hallmark of deep sleep, but how network coherence elevates arousal thresholds to maintain quiescent...

In vertebrates, memory-relevant synaptic plasticity involves postsynaptic rearrangements of glutamate receptors. In contrast, previous work indicates that Drosophila and other invertebrates store memories using presynaptic plasticity of cholinergic synapses. Here, we provide evidence for postsynaptic plasticity at cholinergic output synapses from t...

Slow-wave rhythms characteristic of deep sleep oscillate in the delta band (0.5-4 Hz) and can be found across various brain regions in vertebrates. Across phyla, however, an understanding of the mechanisms underlying oscillations and how these link to behavior remains limited. Here, we discover compound delta oscillations in the sleep-regulating R5...

Neuronal communication across synapses relies on neurotransmitter release from presynaptic active zones (AZs) followed by postsynaptic transmitter detection. Synaptic plasticity homeostatically maintains functionality during perturbations and enables memory formation. Postsynaptic plasticity targets neurotransmitter receptors, but presynaptic mecha...

Slow-wave rhythms characteristic of deep sleep oscillate in the delta band (0.5-4 Hz) and can be found across various brain regions in vertebrates. Across systems it is however unclear how oscillations arise and whether they are the causal functional unit steering behavior. Here, for the first time in any invertebrate, we discover sleep-relevant de...

Synaptic transmission is mediated by neurotransmitter release at presynaptic active zones (AZs) followed by postsynaptic neurotransmitter detection. Plastic changes in transmission maintain functionality during perturbations and enable memory formation. Postsynaptic plasticity targets neurotransmitter receptors, but presynaptic plasticity mechanism...

Stimulus directed behavior is regulated by communication between neurons within neural circuits throughout an animal’s brain. Experience can change the dynamics of neural circuits by modifying specific synaptic connections. However, pinpointing the sites of behavioral-relevant plasticity has proven challenging. Technical advances in controlling and...

Zusammenfassung Zielgerichtetes Verhalten wird durch neuronale Schaltkreise im Gehirn gesteuert. Erfahrungen können die Dynamiken dieser neuronalen Schaltkreise verändern, indem spezifische synaptische Verbindungen modifiziert werden. Die Lokalisierung einer solchen lerninduzierten synaptischen Plastizität hat sich jedoch bis heute als anspruchsvol...

In a constantly changing environment, neuronal circuits need to be updated and adjusted to elicit directed actions. Synaptic plasticity plays an important role in modulating such globally and locally acting networks. The active zone (AZ) is a protein-rich compartment of chemical synapses, where precisely orchestrated molecular interactions control...

Neural information processing depends on precisely timed, Ca2+-activated synaptic vesicle exocytosis from release sites within active zones (AZs), but molecular details are unknown. Here,we identify that the (M)Unc13-family member Unc13A generates release sites and show the physiological relevance of their restrictive AZ targeting. Super-resolution...

Movie S2. Projection View of the Innervation of the MVP2 and M4/6 Neurons in the Horizontal Lobe Tip of the MB Genotype; R83A12-GAL4; UAS-GCaMP6f (MVP2, orange) and R21D02-LexA; lexAop-CD2::mRFP (M4/6 cyan).

Movie S3. Projection View of the Innervation of the MVP2 and V2αV2α′ Neurons in the Vertical Lobe of the MB Genotype; R12G04-LexA; lexAop-rCD2::mRFP (MVP2, orange) and R71D08-GAL4; UAS-mCD8::GFP (V2αV2α′, cyan).

Document S1. Figures S1–S6, Movies S1–S3 and Supplemental Experimental Procedures

Projection of MB112C driven UAS-mCitrine reveals the detailed 3D morphology of MVP2 processes.

In Drosophila, negatively reinforcing dopaminergic neurons also provide the inhibitory control of satiety over appetitive memory expression. Here we show that aversive learning causes a persistent depression of the conditioned odor drive to two downstream feed-forward inhibitory GABAergic interneurons of the mushroom body, called MVP2, or mushroom...

When imaging through tissue, the optical inhomogeneities of the sample generate aberrations that can prevent effective Stimulated Emission Depletion (STED) imaging. This is particularly problematic for 3D-enhanced STED. We present here an adaptive optics implementation that incorporates two adaptive optic elements to enable correction in all beam p...

Optogenetic KC activation via 247-LexA-expressed lexAop-CsChrimson and red light illumination leads to robust calcium responses in M4/6 axons. R21D02-GAL4; UAS-GCaMP6f explant brains monitored with two-photon imaging. Frame rate is 5.92 Hz. Shown are two representative samples before and after addition of the nicotinic receptor antagonist mecamylam...

ChAT and VAChT immunofluorescence in the mushroom body lobes is greatly reduced by OK107-GAL4 directed expression of UAS-ChATRNAi or UAS-VAChTRNAi, respectively (middle panels). Movie shows a representative sample stack at 0.5 μm/frame. All flies were raised and processed for immunostaining in parallel before being imaged using the same confocal se...

Memories are stored in the fan-out fan-in neural architectures of the mammalian cerebellum and hippocampus and the insect mushroom bodies. However, whereas key plasticity occurs at glutamatergic synapses in mammals, the neurochemistry of the memory-storing mushroom body Kenyon cell output synapses is unknown. Here we demonstrate a role for acetylch...

Learning permits animals to attach meaning and context to sensory stimuli. How this information is coded in neural networks in the brain, and appropriately retrieved and utilized to guide behavior, is poorly understood. In the fruit fly olfactory memories of particular value are represented within sparse populations of odor-activated Kenyon cells (...

The fruit fly Drosophila melanogaster has emerged as a popular model to investigate fundamental principles of neural circuit operation. The sophisticated genetics and small brain permit a cellular resolution understanding of innate and learned behavioural processes. Relatively recent genetic and technical advances provide the means to specifically...

During olfactory learning in fruit flies, dopaminergic neurons assign value to odor representations in the mushroom body Kenyon cells. Here we identify a class of downstream glutamatergic mushroom body output neurons (MBONs) called M4/6, or MBON-β2β'2a, MBON-β'2mp, and MBON-γ5β'2a, whose dendritic fields overlap with dopaminergic neuron projections...

Drinking water is innately rewarding to thirsty animals. In addition, the consumed value can be assigned to behavioral actions and predictive sensory cues by associative learning. Here we show that thirst converts water avoidance into water-seeking in naive Drosophila melanogaster. Thirst also permitted flies to learn olfactory cues paired with wat...

Synaptic vesicles (SVs) fuse at a specialized membrane domain called the active zone (AZ), covered by a conserved cytomatrix. How exactly cytomatrix components intersect with SV release remains insufficiently understood. We showed previously that loss of the Drosophila melanogaster ELKS family protein Bruchpilot (BRP) eliminates the cytomatrix (T b...

Dopamine is synonymous with reward and motivation in mammals. However, only recently has dopamine been linked to motivated behaviour and rewarding reinforcement in fruitflies. Instead, octopamine has historically been considered to be the signal for reward in insects. Here we show, using temporal control of neural function in Drosophila, that only...

Synapse formation and maturation requires bidirectional communication across the synaptic cleft. The trans-synaptic Neurexin-Neuroligin complex can bridge this cleft, and severe synapse assembly deficits are found in Drosophila melanogaster neuroligin (Nlg1, dnlg1) and neurexin (Nrx-1, dnrx) mutants. We show that the presynaptic active zone protein...

Plastic changes at the presynaptic sites of the mushroom body (MB) principal neurons called Kenyon cells (KCs) are considered to represent a neuronal substrate underlying olfactory learning and memory. It is generally believed that presynaptic and postsynaptic sites of KCs are spatially segregated. In the MB calyx, KCs receive olfactory input from...

At presynaptic active zones (AZs), the frequently observed tethering of synaptic vesicles to an electron-dense cytomatrix represents a process of largely unknown functional significance. Here, we identified a hypomorphic allele, brpnude, lacking merely the last 1% of the C-terminal amino acids (17 of 1740) of the active zone protein Bruchpilot. In...

Precise apposition of presynaptic and postsynaptic domains is a fundamental property of all neuronal circuits. Experiments in vitro suggest that Neuroligins and Neurexins function as key regulatory proteins in this process. In a genetic screen, we recovered several mutant alleles of Drosophila neuroligin 1 (dnlg1) that cause a severe reduction in b...

Active zones (AZs) are presynaptic membrane domains mediating synaptic vesicle fusion opposite postsynaptic densities (PSDs). At the Drosophila neuromuscular junction, the ELKS family member Bruchpilot (BRP) is essential for dense body formation and functional maturation of AZs. Using a proteomics approach, we identified Drosophila Syd-1 (DSyd-1) a...

Synaptic vesicles fuse at active zone (AZ) membranes where Ca2+ channels are clustered and that are typically decorated by electron-dense projections. Recently, mutants of the Drosophila melanogaster ERC/CAST family protein Bruchpilot (BRP) were shown to lack dense projections (T-bars) and to suffer from Ca2+ channel–clustering defects. In this stu...

Rapid neurotransmission depends on the structural and functional integrity of synaptic connections. How synapses assemble is currently being intensely investigated to help our understanding of neuronal development and synaptic plasticity. Here we focus on the assembly of the presynaptic active zone, which regulates the synaptic vesicle exo/endo-cyc...

Synapses form by an asymmetric association of highly specialized membrane domains: transmitter receptors at the postsynaptic density sense the neurotransmitter signal, while the synaptic vesicles release their content at the presynaptic active zone. Here, macromolecular specializations have evolved that are visible in the transmission electron micr...