Biology subjects

Treiber, C. D.

Publications and source records attributed to Treiber, C. D..

11 recordsLinked to original sources

bioRxiv2026

Dietary magnesium supplement enhances memory through Hippo signaling

Dietary magnesium (Mg2+) supplement enhances memory in mammals and Drosophila, but whether and how Mg2+ changes molecular states of neurons, remains unknown. Here we used single-cell RNA sequencing to map cell-type specific transcriptional responses to memory-enhancing dietary Mg2+. These analyses revealed changes in Hippo-pathway gene expression in memory-relevant {beta} Kenyon Cells (KCs) of the mushroom bodies. Targeted knock-down of Merlin, hippo (hpo) and warts demonstrated requirement in {beta} KCs for Mg2+-enhanced, but not baseline memory. Further study of Hippo signaling identified Yorkie (yki) transcriptional coactivator and DNA-binding partner Scalloped (sd) to be required for baseline and Mg2+-enhanced memory. Moreover, releasing Yki::Sd of inhibition from Tondu-domain containing growth inhibitor (Tgi) specifically in {beta} KCs enhanced memory, independent of diet. Analyses of Yki::Sd target genes identified several required in {beta} KCs for baseline memory, including crb and Glut1 which are also Mg2+-induced in a Hippo-dependent manner in {beta} KCs. These genes suggest that aiding the metabolic demands of long-term memory and facilitating structural neuronal plasticity are key mediators of Mg2+-induced memory enhancement. We propose pharmacological enhancement of Sd-dependent transcription, and activity of particular Sd-target genes may have therapeutic potential for memory disorders.

neuroscience↗

bioRxiv2026

Hunger reconfigures a reward learning circuit into a memory competent mode

Internal states such as hunger dynamically reshape activity across circuits to support resource seeking. Neuromodulation provides a means of controlling such physiological properties of neurons, but how this flexibility regulates memory networks remains unclear. Here, we describe how hunger reconfigures a dopaminergic food-reward circuit between two physiological modes that support memory formation, in Drosophila. Starvation suppresses baseline dopaminergic activity through peptidergic signalling, enabling reward-evoked, large-amplitude dopamine neuron spikes to reinforce learning. This spiking mode can be engaged by sugar consumption and persists beyond feeding, reflecting the fly's satiety state. Persistent dopaminergic large-amplitude spiking reinforces learning and transitions the memory network into a mode that prioritizes consolidation of recently acquired memories. The transition from hunger to satiation is also reflected in the activity of postsynaptic output neurons that shift from a tonic, decorrelated mode that is responsive to dopamine into a bursting, correlated mode in which further dopaminergic modulation is occluded. Therefore, nutrient deprivation reconfigures the memory circuit into a learning competent dopamine-receptive mode, which persistent reinforcing dopamine then switches into a satiated mode driving memory consolidation. Together these processes mechanistically intertwine state-dependent reward-signalling with subsequent memory stabilization through transitions in physiological mode.

neuroscience↗

bioRxiv2026

Transposons contribute to splice-isoform diversity in the Drosophila brain

The extraordinary complexity of the brain depends in part on the vast diversity of mRNA isoforms it expresses, often in a cell-type specific manner. In a recent study, we found that intronic transposable elements (TEs) are spliced into neural transcripts and diversify the splice isoform repertoire of neurons and glia (Treiber and Waddell, 2020). A recent paper by Azad et al. revisits these findings using their TIDAL analysis pipeline applied to our published data (Azad et al., 2024). Their analysis did not find any of the splicing reads we reported, and although they used RT-PCR to test seven of the 264 TE-gene pairs we had previously reported, they failed to validate TE-gene splicing in any of them. Here, we conduct a quantitative analysis of TE exonisation and show that intronic TE insertions are frequently recruited as alternative exons, with exon usage ranging from rare events to near-complete inclusion in transcripts. We implement this analysis in an improved version of our TEChim software, and present clear support for TE-gene splicing at the seven loci tested by Azad et al. We also identify methodological issues in the experimental and computational design of the Azad et al. study that likely explain their failure to detect TE-gene chimeras, while demonstrating that TE-gene splicing can be detected by RT-PCR under appropriate experimental conditions. Together, our data demonstrates that TE splice isoforms are not rare artefacts but measurable and biologically relevant features of the Drosophila brain transcriptome that may contribute to the molecular complexity and functional adaptability of the brain.

genomics↗

bioRxiv2026

Genetic sex of enteric neurons enables ovarian relaxin togate maternal gut plasticity

Animals must align intestinal plasticity and feeding with reproductive state, yet the checkpoint that gates these adaptations is unknown. Here we show that an ovary-to-enteric-neuron axis gates the onset of maternal gut plasticity in Drosophila. Genetic sex establishes endocrine competence in a subset of enteric neurons via the sex determination pathway, enabling female-specific expression of the relaxin-family receptor Lgr3. After mating, steroid signalling increases Lgr3 receptor expression, priming these neurons for reproductive adaptation. Once oocytes mature fully, follicle cells secrete the relaxin-like hormone dILP8, which activates Lgr3 to trigger gut enlargement and increased feeding. Disrupting the sex determination pathway in enteric neurons, Lgr3, or ovarian dILP8 prevents gut enlargement and reduces feeding. Thus, genetic sex establishes competence, steroid signalling primes it, and ovarian relaxin triggers it, defining a maternal intestinal plasticity checkpoint that ensures gut adaptations initiate only once reproduction is underway and energy demands peak. Our findings delineate an ovary-to-enteric-neuron axis that couples reproductive state to maternal gut plasticity.

physiology↗

bioRxiv2025

Visceral signaling of post-ingestive malaise directs memory updating in Drosophila

Consolidation is a time when labile memories transition to a stable form. Malaise learning in Drosophila reveals consolidation to also permit memory updating. Flies taught to associate one of two odors with toxin-tainted sugar initially express conditioned odor approach, that following consolidation switches to avoidance. Behavioral reversal emerges from dopaminergic update of parallel memories for the two trained odors. Differential serotoninergic modulation of specific aversive and rewarding dopaminergic neuron subtypes permits post-ingestive intoxication to suppress consolidation of initial odor-sugar memory and simultaneously invert reward memory plasticity into "safety" memory for the odor experienced without food. Fat body release of the Toll-ligand activating protease modSP, and resilience factor Turandot A, instruct malaise updates by triggering autocrine Toll signaling in the same brain dopaminergic neurons that form and consolidate initial sugar memory. This neural mechanism overcomes the credit assignment problem of delayed post-ingestive reinforcement by updating earlier memories of the trained odors.

neuroscience↗

bioRxiv2024

Tango-seq: overlaying transcriptomics on connectomics to identify neurons downstream of Drosophila clock neurons

Knowing how neural circuits change with neuronal plasticity and differ between individuals is important to fully understand behavior. Connectomes are typically assembled using electron microscopy, but this is low throughput and impractical for analyzing plasticity or mutations. Here, we modified the trans-Tango genetic circuit-tracing technique to identify neurons synaptically downstream of Drosophila s-LNv clock neurons, which show 24hr plasticity rhythms. s-LNv target neurons were labeled specifically in adult flies using a nuclear reporter gene, which facilitated their purification and then single cell sequencing. We call this Tango-seq, and it allows transcriptomic data - and thus cell identity - to be overlayed on top of anatomical data. We found that s-LNvs preferentially make synaptic connections with a subset of the CNMa+ DN1p clock neurons, and that these are likely plastic connections. We also identified synaptic connections between s-LNvs and mushroom body Kenyon cells. Tango-seq should be a useful addition to the connectomics toolkit.

neuroscience↗

bioRxiv2023

Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration

Parkinsons disease (PD) targets some dopamine (DA) neurons more than others. Sex differences offer insights, with females more protected from DA neurodegeneration. The mammalian vesicular glutamate transporter VGLUT2 and Drosophila ortholog dVGLUT have been implicated as modulators of DA neuron resilience. However, the mechanisms by which VGLUT2/dVGLUT protects DA neurons remain unknown. We discovered DA neuron dVGLUT knockdown increased mitochondrial reactive oxygen species in a sexually dimorphic manner in response to depolarization or paraquat-induced stress, males being especially affected. DA neuron dVGLUT also reduced ATP biosynthetic burden during depolarization. RNA sequencing of VGLUT+ DA neurons in mice and flies identified candidate genes that we functionally screened to further dissect VGLUT-mediated DA neuron resilience across PD models. We discovered transcription factors modulating dVGLUT-dependent DA neuroprotection and identified dj-1{beta} as a regulator of sex-specific DA neuron dVGLUT expression. Overall, VGLUT protects DA neurons from PD-associated degeneration by maintaining mitochondrial health.

neuroscience↗

bioRxiv2022

Gliotransmission of D-serine promotes thirst-directed behaviors in Drosophila

Thirst emerges from a range of cellular changes that ultimately motivate an animal to consume water. Although thirst-responsive neuronal signals have been reported, the full complement of brain responses is unclear. Here we identify molecular and cellular adaptations in the brain using single-cell sequencing of water deprived Drosophila. Water deficiency primarily altered the glial transcriptome. Screening the regulated genes revealed astrocytic expression of the astray-encoded phosphoserine phosphatase to bi-directionally regulate water consumption. Astray synthesizes the gliotransmitter D-serine and vesicular release from astrocytes is required for drinking. Moreover, dietary D-serine rescues aay-dependent drinking deficits while facilitating water consumption and expression of water-seeking memory. D-serine action requires binding to neuronal NMDA-type glutamate receptors. Fly astrocytes contribute processes to tripartite synapses and the proportion of astrocytes that are themselves activated by glutamate increases with water deprivation. We propose that thirst elevates astrocytic D-serine release, which awakens quiescent glutamatergic circuits to enhance water procurement.

neuroscience↗

bioRxiv2019

A single-cell transcriptomic atlas of the adult Drosophila ventral nerve cord

The Drosophila ventral nerve cord (VNC) receives and processes descending signals from the brain to produce a variety of coordinated locomotor outputs. It also integrates sensory information from the periphery and sends ascending signals to the brain. We used single-cell transcriptomics to generate an unbiased classification of cellular diversity in the VNC of five-day old adult flies. We produced an atlas of 26,000 high-quality cells, representing more than 100 transcriptionally distinct cell types. The predominant gene signatures defining neuronal cell types reflect shared developmental histories based on the neuroblast from which cells were derived, as well as their birth order. Cells could also be assigned to specific neuromeres using adult Hox gene expression. This single-cell transcriptional atlas of the adult fly VNC will be a valuable resource for future studies of neurodevelopment and behavior.

neuroscience↗

bioRxiv2019

Transposon expression in the Drosophila brain is driven by neighbouring genes and diversifies the neural transcriptome

Somatic transposition in neural tissue could contribute to neuropathology and individuality, but its prevalence is debated. We used single-cell mRNA sequencing to map transposon expression in the Drosophila midbrain. We found that neural transposon expression is driven by cellular genes. Every expressed transposon is resident in at least one cellular gene with a matching expression pattern. A new long-read RNA sequencing approach revealed that coexpression is a physical link in the form of abundant chimeric transposon-gene mRNAs. We identified 148 genes where transposons introduce cryptic splice sites into the nascent transcript and thereby produce many additional mRNAs. Some genes exclusively produce chimeric mRNAs with transposon sequence and on average transposon-gene chimeras account for 20% of the mRNAs produced from a given gene. Transposons therefore significantly expand the neural transcriptome. We propose that chimeric mRNAs produced by splicing into polymorphic transposons may contribute to functional differences between individual cells and animals.

genetics↗

bioRxiv2017

Cellular diversity in the Drosophila midbrain revealed by single-cell transcriptomics

To understand the brain, molecular details need to be overlaid onto neural wiring diagrams so that synaptic mode, neuromodulation and critical signaling operations can be considered. Single-cell transcriptomics provide a unique opportunity to collect this information. Here we present an initial analysis of thousands of individual cells from Drosophila midbrain, that were acquired using Drop-Seq. A number of approaches permitted the assignment of transcriptional profiles to several major brain regions and cell-types. Expression of biosynthetic enzymes and reuptake mechanisms allows all the neurons to be typed according to the neurotransmitter or neuromodulator that they produce and presumably release. Some neuropeptides are preferentially co-expressed in neurons using a particular fast-acting transmitter, or monoamine. Neuromodulatory and neurotransmitter receptor subunit expression illustrates the potential of these molecules in generating complexity in neural circuit function. This cell atlas dataset provides an important resource to link molecular operations to brain regions and complex neural processes.

neuroscience↗