@article {1788, title = {Imaging brain activity during complex social behaviors in Drosophila with Flyception2.}, journal = {Nat Commun}, volume = {11}, year = {2020}, month = {2020 01 30}, pages = {623}, abstract = {

Optical in vivo recordings from freely walking Drosophila are currently possible only for limited behaviors. Here, we expand the range of accessible behaviors with a retroreflective marker-based tracking and ratiometric brain imaging system, permitting brain activity imaging even in copulating male flies. We discover that P1 neurons, active during courtship, are inactive during copulation, whereas GABAergic mAL neurons remain active during copulation, suggesting a countervailing role of mAL in opposing P1 activity during mating.

}, keywords = {Animals, Brain, Copulation, Courtship, Drosophila, Drosophila Proteins, Female, GABAergic Neurons, Male, Neuroimaging, Neurons, Olfactory Cortex, Sexual Behavior, Animal, Social Behavior}, issn = {2041-1723}, doi = {10.1038/s41467-020-14487-7}, author = {Grover, Dhruv and Katsuki, Takeo and Li, Jinfang and Dawkins, Thomas J and Greenspan, Ralph J} } @article {1693, title = {Asymmetric ephaptic inhibition between compartmentalized olfactory receptor neurons.}, journal = {Nat Commun}, volume = {10}, year = {2019}, month = {2019 04 05}, pages = {1560}, abstract = {

In the Drosophila antenna, different subtypes of olfactory receptor neurons (ORNs) housed in the same sensory hair (sensillum) can inhibit each other non-synaptically. However, the mechanisms underlying this underexplored form of lateral inhibition remain unclear. Here we use recordings from pairs of sensilla impaled by the same tungsten electrode to demonstrate that direct electrical ("ephaptic") interactions mediate lateral inhibition between ORNs. Intriguingly, within individual sensilla, we find that ephaptic lateral inhibition is asymmetric such that one ORN exerts greater influence onto its neighbor. Serial block-face scanning electron microscopy of genetically identified ORNs and circuit modeling indicate that asymmetric lateral inhibition reflects a surprisingly simple mechanism: the physically larger ORN in a pair corresponds to the dominant neuron in ephaptic interactions. Thus, morphometric differences between compartmentalized ORNs account for highly specialized inhibitory interactions that govern information processing at the earliest stages of olfactory coding.

}, keywords = {Animals, Drosophila, Imaging, Three-Dimensional, Models, Biological, Olfactory Pathways, Olfactory Receptor Neurons, Sensilla, Smell}, issn = {2041-1723}, doi = {10.1038/s41467-019-09346-z}, author = {Zhang, Ye and Tsang, Tin Ki and Bushong, Eric A and Chu, Li-An and Chiang, Ann-Shyn and Ellisman, Mark H and Reingruber, J{\"u}rgen and Su, Chih-Ying} } @article {1695, title = {High-quality ultrastructural preservation using cryofixation for 3D electron microscopy of genetically labeled tissues.}, journal = {Elife}, volume = {7}, year = {2018}, month = {2018 05 11}, abstract = {

Electron microscopy (EM) offers unparalleled power to study cell substructures at the nanoscale. Cryofixation by high-pressure freezing offers optimal morphological preservation, as it captures cellular structures instantaneously in their near-native state. However, the applicability of cryofixation is limited by its incompatibility with diaminobenzidine labeling using genetic EM tags and the high-contrast staining required for serial block-face scanning electron microscopy (SBEM). In addition, it is challenging to perform correlated light and electron microscopy (CLEM) with cryofixed samples. Consequently, these powerful methods cannot be applied to address questions requiring optimal morphological preservation. Here, we developed an approach that overcomes these limitations; it enables genetically labeled, cryofixed samples to be characterized with SBEM and 3D CLEM. Our approach is broadly applicable, as demonstrated in cultured cells, olfactory organ and mouse brain. This optimization exploits the potential of cryofixation, allowing for quality ultrastructural preservation for diverse EM applications.

}, keywords = {Animal Structures, Animals, Brain, Cryopreservation, Drosophila, Imaging, Three-Dimensional, Mice, Microscopy, Electron, Scanning, Sense Organs}, issn = {2050-084X}, doi = {10.7554/eLife.35524}, author = {Tsang, Tin Ki and Bushong, Eric A and Boassa, Daniela and Hu, Junru and Romoli, Benedetto and Phan, Sebastien and Dulcis, Davide and Su, Chih-Ying and Ellisman, Mark H} } @article {1697, title = {A neural data structure for novelty detection.}, journal = {Proc Natl Acad Sci U S A}, volume = {115}, year = {2018}, month = {2018 12 18}, pages = {13093-13098}, abstract = {

Novelty detection is a fundamental biological problem that organisms must solve to determine whether a given stimulus departs from those previously experienced. In computer science, this problem is solved efficiently using a data structure called a Bloom filter. We found that the fruit fly olfactory circuit evolved a variant of a Bloom filter to assess the novelty of odors. Compared with a traditional Bloom filter, the fly adjusts novelty responses based on two additional features: the similarity of an odor to previously experienced odors and the time elapsed since the odor was last experienced. We elaborate and validate a framework to predict novelty responses of fruit flies to given pairs of odors. We also translate insights from the fly circuit to develop a class of distance- and time-sensitive Bloom filters that outperform prior filters when evaluated on several biological and computational datasets. Overall, our work illuminates the algorithmic basis of an important neurobiological problem and offers strategies for novelty detection in computational systems.

}, keywords = {Algorithms, Animals, Drosophila, Models, Biological, Nerve Net, Neural Networks (Computer), Odorants, Olfactory Pathways}, issn = {1091-6490}, doi = {10.1073/pnas.1814448115}, author = {Dasgupta, Sanjoy and Sheehan, Timothy C and Stevens, Charles F and Navlakha, Saket} } @article {166, title = {A comprehensive wiring diagram of the protocerebral bridge for visual information processing in the Drosophila brain.}, journal = {Cell Rep}, volume = {3}, year = {2013}, month = {2013 May 30}, pages = {1739-53}, abstract = {

How the brain perceives sensory information and generates meaningful behavior depends critically on its underlying circuitry. The protocerebral bridge (PB) is a major part of the insect central complex (CX), a premotor center that may be analogous to the human basal ganglia. Here, by deconstructing hundreds of PB single neurons and reconstructing them into a common three-dimensional framework, we have constructed a comprehensive map of PB circuits with labeled polarity and predicted directions of information flow. Our analysis reveals a highly ordered information processing system that involves directed information flow among CX subunits through 194 distinct PB neuron types. Circuitry properties such as mirroring, convergence, divergence, tiling, reverberation, and parallel signal propagation were observed; their functional and evolutional significance is discussed. This layout of PB neuronal circuitry may provide guidelines for further investigations on transformation of sensory (e.g., visual) input into locomotor commands in fly brains.

}, keywords = {Animals, Brain, Drosophila, Models, Biological, Neurons}, issn = {2211-1247}, doi = {10.1016/j.celrep.2013.04.022}, author = {Lin, Chih-Yung and Chuang, Chao-Chun and Hua, Tzu-En and Chen, Chun-Chao and Dickson, Barry J and Greenspan, Ralph J and Chiang, Ann-Shyn} } @article {143, title = {Activation of EGFR and ERK by rhomboid signaling regulates the consolidation and maintenance of sleep in Drosophila.}, journal = {Nat Neurosci}, volume = {10}, year = {2007}, month = {2007 Sep}, pages = {1160-7}, abstract = {

Epidermal growth factor receptor (EGFR) signaling in the mammalian hypothalamus is important in the circadian regulation of activity. We have examined the role of this pathway in the regulation of sleep in Drosophila melanogaster. Our results demonstrate that rhomboid (Rho)- and Star-mediated activation of EGFR and ERK signaling increases sleep in a dose-dependent manner, and that blockade of rhomboid (rho) expression in the nervous system decreases sleep. The requirement of rho for sleep localized to the pars intercerebralis, a part of the fly brain that is developmentally and functionally analogous to the hypothalamus in vertebrates. These results suggest that sleep and its regulation by EGFR signaling may be ancestral to insects and mammals.

}, keywords = {Analysis of Variance, Animals, Animals, Genetically Modified, Behavior, Animal, Drosophila, Drosophila Proteins, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Gene Expression Regulation, Developmental, Membrane Proteins, Motor Activity, Receptor, Epidermal Growth Factor, Signal Transduction, Sleep}, issn = {1097-6256}, doi = {10.1038/nn1957}, author = {Foltenyi, Krisztina and Greenspan, Ralph J and Newport, John W} } @article {146, title = {The nature of genetic influences on behavior: lessons from "simpler" organisms.}, journal = {Am J Psychiatry}, volume = {163}, year = {2006}, month = {2006 Oct}, pages = {1683-94}, abstract = {

Substantial advances have been made in recent years in the understanding of the genetic basis of behavior in "simpler" organisms, especially the mouse and the fruit fly Drosophila. The authors examine the degree of similarity between the genetic underpinnings of psychiatric illness and genetic influences on behavior in such simpler organisms. Six topics are reviewed: 1) the extent of natural genetic variation, 2) the multigenic nature of natural variation, 3) the impact of individual genes on multiple traits, 4) gene-environment interactions, 5) genetic effects on the environment, and 6) gene-by-sex interactions. The results suggest that the pattern of results emerging in psychiatric genetics is generally consistent with the findings of behavioral genetics in simpler organisms. Across the animal kingdom, individual differences in behavior are nearly always influenced by genetic factors which, in turn, result from a substantial number of individual genes, each with a small effect. Nearly all genes that affect behavior influence multiple phenotypes. The impact of individual genes can be substantially modified by other genes and/or by environmental experiences. Many animals alter their environment, and the nature of that alteration is influenced by genes. For some behaviors, the pathway from genes to behavior differs meaningfully in males and females. With respect to the broad patterns of genetic influences on behavior, Homo sapiens appears to be typical of other animal species.

}, keywords = {Animals, Drosophila, Genetics, Behavioral, Humans, Mental Disorders, Mice, Physiology, Comparative}, issn = {0002-953X}, doi = {10.1176/ajp.2006.163.10.1683}, author = {Kendler, Kenneth S and Greenspan, Ralph J} } @article {147, title = {Dopaminergic modulation of arousal in Drosophila.}, journal = {Curr Biol}, volume = {15}, year = {2005}, month = {2005 Jul 12}, pages = {1165-75}, abstract = {

BACKGROUND: Arousal levels in the brain set thresholds for behavior, from simple to complex. The mechanistic underpinnings of the various phenomena comprising arousal, however, are still poorly understood. Drosophila behaviors have been studied that span different levels of arousal, from sleep to visual perception to psychostimulant responses.

RESULTS: We have investigated neurobiological mechanisms of arousal in the Drosophila brain by a combined behavioral, genetic, pharmacological, and electrophysiological approach. Administration of methamphetamine (METH) suppresses sleep and promotes active wakefulness, whereas an inhibitor of dopamine synthesis promotes sleep. METH affects courtship behavior by increasing sexual arousal while decreasing successful sexual performance. Electrophysiological recordings from the medial protocerebrum of wild-type flies showed that METH ingestion has rapid and detrimental effects on a brain response associated with perception of visual stimuli. Recordings in genetically manipulated animals show that dopaminergic transmission is required for these responses and that visual-processing deficits caused by attenuated dopaminergic transmission can be rescued by METH.

CONCLUSIONS: We show that changes in dopamine levels differentially affect arousal for behaviors of varying complexity. Complex behaviors, such as visual perception, degenerate when dopamine levels are either too high or too low, in accordance with the inverted-U hypothesis of dopamine action in the mammalian brain. Simpler behaviors, such as sleep and locomotion, show graded responses that follow changes in dopamine level.

}, keywords = {Animals, Animals, Genetically Modified, Arousal, Brain, Dopa Decarboxylase, Dopamine, Dose-Response Relationship, Drug, Drosophila, Drosophila Proteins, Dynamins, Electrophysiology, Methamphetamine, Mutation, Sexual Behavior, Animal, Sleep, Visual Perception}, issn = {0960-9822}, doi = {10.1016/j.cub.2005.05.025}, author = {Andretic, Rozi and van Swinderen, Bruno and Greenspan, Ralph J} } @article {149, title = {Salience modulates 20-30 Hz brain activity in Drosophila.}, journal = {Nat Neurosci}, volume = {6}, year = {2003}, month = {2003 Jun}, pages = {579-86}, abstract = {

Fruit flies selectively orient toward the visual stimuli that are most salient in their environment. We recorded local field potentials (LFPs) from the brains of Drosophila melanogaster as they responded to the presentation of visual stimuli. Coupling of salience effects (odor, heat or novelty) to these stimuli modulated LFPs in the 20-30 Hz range by evoking a transient, selective increase. We demonstrated the association of these responses with behavioral tracking and initiated a genetic approach to investigating neural correlates of perception.

}, keywords = {Action Potentials, Animals, Attention, Behavior, Animal, Brain, Cues, Drosophila, Drosophila Proteins, Exploratory Behavior, Mutation, Neurons, Orientation, Retina, Smell, Synaptic Transmission, Thermosensing, Visual Pathways, Visual Perception}, issn = {1097-6256}, doi = {10.1038/nn1054}, author = {van Swinderen, Bruno and Greenspan, Ralph J} }