@article {65263, title = {The neuropeptide Drosulfakinin regulates social isolation-induced aggression in Drosophila.}, journal = {Journal of Experimental Biology}, volume = {223}, year = {2020}, month = {2020 Jan 03}, abstract = {

Social isolation strongly modulates behavior across the animal kingdom. We utilized the fruit fly to study social isolation-driven changes in animal behavior and gene expression in the brain. RNA-seq identified several head-expressed genes strongly responding to social isolation or enrichment. Of particular interest, social isolation downregulated expression of the gene encoding the neuropeptide (), the homologue of vertebrate cholecystokinin (CCK), which is critical for many mammalian social behaviors. knockdown significantly increased social isolation-induced aggression. Genetic activation or silencing of neurons each similarly increased isolation-driven aggression. Our results suggest a U-shaped dependence of social isolation-induced aggressive behavior on signaling, similar to the actions of many neuromodulators in other contexts.

}, issn = {1477-9145}, doi = {10.1242/jeb.207407}, author = {Agrawal, Pavan and Kao, Damian and Chung, Phuong and Looger, Loren L} } @article {64875, title = {Enabling cell-type-specific behavioral epigenetics in Drosophila: a modified high-yield INTACT method reveals the impact of social environment on the epigenetic landscape in dopaminergic neurons.}, journal = {BMC Biology}, volume = {17}, year = {2019}, month = {2019 Apr 10}, pages = {30}, abstract = {

BACKGROUND: Epigenetic mechanisms play fundamental roles in brain function and behavior and stressors such as social isolation can alter animal behavior via epigenetic mechanisms. However, due to cellular heterogeneity, identifying cell-type-specific epigenetic changes in the brain is challenging. Here, we report the first use of a modified isolation of nuclei tagged in specific cell type (INTACT) method in behavioral epigenetics of Drosophila melanogaster, a method we call mini-INTACT.

RESULTS: Using ChIP-seq on mini-INTACT purified dopaminergic nuclei, we identified epigenetic signatures in socially isolated and socially enriched Drosophila males. Social experience altered the epigenetic landscape in clusters of genes involved in transcription and neural function. Some of these alterations could be predicted by expression changes of four transcription factors and the prevalence of their binding sites in several clusters. These transcription factors were previously identified as activity-regulated genes, and their knockdown in dopaminergic neurons reduced the effects of social experience on sleep.

CONCLUSIONS: Our work enables the use of Drosophila as a model for cell-type-specific behavioral epigenetics and establishes that social environment shifts the epigenetic landscape in dopaminergic neurons. Four activity-related transcription factors are required in dopaminergic neurons for the effects of social environment on sleep.

}, issn = {1741-7007}, doi = {10.1186/s12915-019-0646-4}, author = {Agrawal, Pavan and Chung, Phuong and Heberlein, Ulrike and Kent, Clement} } @article {49013, title = {Repetitive aggressive encounters generate a long-lasting internal state in Drosophila melanogaster males.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, year = {2018}, month = {2018 Jan 16}, pages = {1099-104}, abstract = {

Multiple studies have investigated the mechanisms of aggressive behavior in Drosophila; however, little is known about the effects of chronic fighting experience. Here, we investigated if repeated fighting encounters would induce an internal state that could affect the expression of subsequent behavior. We trained wild-type males to become winners or losers by repeatedly pairing them with hypoaggressive or hyperaggressive opponents, respectively. As described previously, we observed that chronic losers tend to lose subsequent fights, while chronic winners tend to win them. Olfactory conditioning experiments showed that winning is perceived as rewarding, while losing is perceived as aversive. Moreover, the effect of chronic fighting experience generalized to other behaviors, such as gap-crossing and courtship. We propose that in response to repeatedly winning or losing aggressive encounters, male flies form an internal state that displays persistence and generalization; fight outcomes can also have positive or negative valence. Furthermore, we show that the activities of the PPL1-γ1pedc dopaminergic neuron and the MBON-γ1pedc\>α/β mushroom body output neuron are required for aversion to an olfactory cue associated with losing fights.

}, issn = {1091-6490}, doi = {10.1073/pnas.1716612115}, author = {Kim, Yong-Kyu and Saver, Mathias and Simon, Jasper and Kent, Clement F and Shao, Lisha and Eddison, Mark and Agrawal, Pavan and Texada, Michael and Truman, James W and Heberlein, Ulrike} } @article {49485, title = {Social isolation-induced epigenetic and transcriptional changes in Drosophila dopaminergic neurons.}, journal = {bioRxiv}, year = {2018}, month = {2018 Oct 14}, abstract = {Epigenetic mechanisms play fundamental roles in brain function and behavior and stressors such as social isolation can alter animal behavior via epigenetic mechanisms. However, due to cellular heterogeneity, identifying cell-type-specific epigenetic changes in the brain is challenging. Here we report first use of a modified INTACT method in behavioral epigenetics of Drosophila: a method we call mini-INTACT. Using ChIP-seq on mini-INTACT purified dopaminergic nuclei, we identified epigenetic signatures in socially-isolated and socially-enriched Drosophila males. Social experience altered the epigenetic landscape in clusters of genes involved in transcription and neural function. Some of these alterations were predicted by expression changes of four transcription factors and the prevalence of their binding sites in several clusters. These transcription factors were previously identified as activity-regulated genes and their knockdown in dopaminergic neurons reduced the effects of social experience on sleep. Our work enables the use of Drosophila as a model for cell-type-specific behavioral epigenetics. }, doi = {10.1101/443226}, author = {Agrawal, Pavan and Chung, Phuong and Heberlein, Ulrike and Kent, Clement F} } @article {45332, title = {ChIP for hox proteins from Drosophila imaginal discs.}, journal = {Methods in Molecular Biology}, volume = {1196}, year = {2014}, month = {2014 August 15}, pages = {241-53}, abstract = {

Chromatin immunoprecipitation (ChIP) is a technique that reveals in vivo location of a protein bound to DNA. ChIP coupled with DNA microarrays (ChIP-chip) or next-generation sequencing (ChIP-seq) allows for identification of binding sites of transcription factors on a global scale. Here we describe a protocol for ChIP to identify binding of the Ultrabithorax (Ubx) Hox transcription factors from imaginal discs of Drosophila larvae. The protocol can be extended to other model organisms and transcription factors.

}, issn = {1940-6029}, doi = {10.1007/978-1-4939-1242-1_15}, author = {Agrawal, Pavan and Shashidhara, L S} }