Biology subjects

Tumkaya, T.

Publications and source records attributed to Tumkaya, T..

8 recordsLinked to original sources

bioRxiv2025

Entirely synthetic memory inception via dual optogenetic activation of sensory and dopaminergic neurons

Associative conditioning is a fundamental learning paradigm that links salient stimuli to appropriate behavior. The vinegar fly is an important memory model that can associate odors with rewarding or punishing reinforcement stimuli via distinct sets of dopaminergic neurons. While much is known about learning, a crucial question remains: is the simple co-activation of sensory and neuromodulatory dopaminergic neurons sufficient to induce memory formation? To address this, we systematically replaced natural stimuli, namely odor-evoked activity, punishment, and reward signals, with optogenetic activation of corresponding neurons, both individually and in combination. In all cases, including a full-substitution paradigm where both olfactory activity and reinforcement dopamine signals were replaced, optogenetic activation successfully implanted synthetic memories. These findings provide a clear answer: simple coincident, rectangular-pulse sensory and neuromodulatory stimulation can instruct associative memory formation. We conclude that associative memory does not have strict requirements for temporal or ensemble activity patterns in olfactory or dopaminergic neurons that are specific to natural stimuli (e.g. odorants, sugar, or pain); rather, simple coincidence is an effective driver of memory inception. These findings open new avenues for manipulating and studying memory formation with all-optical control.

animal behavior and cognition↗

bioRxiv2021

Patient brain organoids identify a link between the 16p11.2 copy number variant and the RBFOX1 gene.

Copy number variants (CNVs) that delete or duplicate 30 genes within the 16p11.2 genomic region give rise to a range of neurodevelopmental phenotypes with high penetrance in humans. Despite the identification of this small region, the mechanisms by which 16p11.2 CNVs lead to disease are unclear. Relevant models, like human cortical organoids (hCOs), are needed to understand the human-specific mechanisms of neurodevelopmental disease. We generated hCOs from 18 patients and controls, profiling 167,958 cells with single cell (sc)RNA-seq. Analysis revealed neuronal-specific differential expression of genes outside of the 16p11.2 region that were related to cell-cell adhesion, neuronal projection growth, and neurodevelopmental disorders. Furthermore, 16p11.2 deletion syndrome organoids exhibited reduced mRNA and protein levels of RBFOX1, a gene which can also harbor CNVs linked to neurodevelopmental phenotypes. We found that many genes previously shown to be regulated by RBFOX1 are also perturbed in organoids from patients with 16p11.2 deletion syndrome, and thus identified a novel link between independent CNVs associated with neuronal development and autism. Overall, this work suggests convergent signaling, which indicates the possibility of a common therapeutic mechanism across multiple rare neuronal diseases.

neuroscience↗

bioRxiv2021

Most primary olfactory neurons have individually neutral effects on behavior

Animals use olfactory receptors to navigate mates, food, and danger. However, for complex olfactory systems, it is unknown what proportion of primary olfactory sensory neurons can individually drive avoidance or attraction. Similarly, the rules that govern behavioral responses to receptor combinations are unclear. We used optogenetic analysis in Drosophila to map the behavior elicited by olfactory-receptor neuron (ORN) classes: just one-fifth of ORN-types drove either avoidance or attraction. Although wind and hunger are closely linked to olfaction, neither had much effect on single-class responses. Several pooling rules have been invoked to explain how ORN types combine their behavioral influences; we activated two-way combinations and compared patterns of single- and double-ORN responses: these comparisons were inconsistent with simple pooling. We infer that the majority of primary olfactory sensory neurons have neutral behavioral effects individually, but participate in broad, odor-elicited ensembles with potent behavioral effects arising from complex interactions.

animal behavior and cognition↗

bioRxiv2021

DRUG-seq Provides Unbiased Biological Activity Readouts for Drug Discovery

Unbiased transcriptomic RNA-seq data has provided deep insights about biological processes. However, its impact in drug discovery has been narrow given high costs and low throughput. Proof-of-concept studies with Digital RNA with pertUrbation of Genes (DRUG)-seq demonstrated the potential to address this gap. We extended the DRUG-seq platform by subjecting it to rigorous testing and by adding an open-source analysis pipeline. The results demonstrate high reproducibility and ability to resolve the mechanism(s) of action for a diverse set of compounds. Overall, the protocol and open-source analysis pipeline are a step towards industrializing RNA-seq for high complexity transcriptomics studies performed at a saturating scale.

genomics↗

bioRxiv2019

Optogenetic olfactory behavior depends on illumination characteristics

Optogenetics has become an important tool for the study of behavior, enabling neuroscientists to infer causations by examining behavior after activating genetically circumscribed neurons with light. Light-induced neural activity is affected by illumination parameters used in experiments, such as intensity, duration, and frequency. Here, we hypothesized that the intensity of light and the presence of oscillations in illumination would alter optogenetically induced olfactory behaviours. To test this, we activated olfactory receptor neurons (ORNs) in Drosophila by using either static or pulsed light stimuli across a range of light intensities. The various regimes elicited distinct behavioral valence responses (attraction, aversion, indifference) from several ORN types. Our results demonstrate the importance of both frequency and intensity for interpreting optogenetic behavioral experiments accurately; successfully generalizing optogenetic results requires the use of more than a single illumination regime.

neuroscience↗

bioRxiv2018

Moving beyond P values: Everyday data analysis with estimation plots

Introduction Introduction The two-groups design is... Significance testing obscures... Even when fully visualized,... Five key advantages of... Estimation graphics are... Conclusion Author Contributions Funding sources Code Availability Guide to using DABEST Web application Google Colaboratory Python Matlab DABEST-Python in R References Over the past 75 years, a number of statisticians have advised that the data-analysis method known as null- hypothesis significance testing (NHST) should be deprecated (Berkson, 1942; Halsey et al., 2015). The l ...

bioinformatics↗

bioRxiv2018

The Drosophila microbiome has a limited influence on sleep, activity, and courtship behaviors

In animals, commensal microbes modulate various physiological functions, including behavior. While microbiota exposure is required for normal behavior in mammals, it is not known how widely this dependency is present in other animal species. We proposed the hypothesis that the microbiome has a major influence on the behavior of the vinegar fly (Drosophila melanogaster), a major invertebrate model organism. Several assays were used to test the contribution of the microbiome on some well-characterized behaviors: defensive behavior, sleep, locomotion, and courtship in microbe-bearing, control flies and two generations of germ-free animals. None of the behaviors were largely influenced by the absence of a microbiome, and the small or moderate effects were not generalizable between replicates and/or generations. These results refute the hypothesis, indicating that the Drosophila microbiome does not have a major influence over several behaviors fundamental to the animals survival and reproduction. The impact of commensal microbes on animal behaviour may not be broadly conserved.

neuroscience↗

bioRxiv2018

A systematic review and meta-analysis of Drosophila short-term-memory genetics: robust reproducibility, but little independent replication

Geneticists use olfactory conditioning in Drosophila to identify learning genes; however, little is known about how these genes are integrated into short-term memory (STM) pathways. Here, we investigated the hypothesis that the STM evidence base is weak. We performed systematic review and meta-analysis of the field. Using metrics to quantify variation between discovery articles and follow-up studies, we found that seven genes were both highly replicated, and highly reproducible. However, ~80% of STM genes have never been replicated. While only a few studies investigated interactions, the reviewed genes could account for >1000% memory. This large summed effect size could indicate irreproducibility, many shared pathways, or that current assay protocols lack the specificity needed to identify core plasticity genes. Mechanistic theories of memory will require the convergence of evidence from system, circuit, cellular, molecular, and genetic experiments; systematic data synthesis is an essential tool for integrated neuroscience.

animal behavior and cognition↗