@article {69515, title = {Recent experience and internal state shape local search strategies in flies}, journal = {Curr Biol}, year = {2026}, month = {2026 Mar 18}, abstract = {

After finding food, a foraging animal must decide whether to continue feeding or to explore the environment for potentially better options. One strategy to negotiate this tradeoff is to perform local searches around the food while repeatedly returning to feed. We studied this behavior in flies and used genetic tools to uncover the underlying behavioral strategies. Over time, flies gradually expand their search, shifting from primarily exploiting food sources to exploring the environment, a change likely driven by increased satiety. We found that flies{\textquoteright} search patterns preserve these dynamics even as the overall range of the search is modulated by starvation. In contrast, search induced by optogenetic activation of sugar-sensing neurons does not show these dynamics. We asked what navigational strategies underlie local search. Using a generative model, we found that a change in locomotor pattern after food consumption could account for repeated returns to the food, but not the relatively direct return trajectories that flies make even from far away. Such trajectories likely rely on alternative strategies, such as path integration or sensory taxis. We tested this by individually silencing their likely neural components, the compass system, olfaction, and hygrosensation. The only substantial effect was from perturbing hygrosensation, which reduced the number of long exploratory trips with subsequent return to the food. Our study illustrates that local search comprises multiple behavioral features that evolve over time based on both internal and external factors, providing a path toward uncovering the underlying neural mechanisms.

}, doi = {10.1016/j.cub.2026.02.037/}, url = {https://https://doi.org/10.1016/j.cub.2026.02.037/content/early/2024/06/28/2024.06.26.600764}, author = {Goldschmidt, Dennis and Guo, Yipei and Chitnis, Shivam S and Christoforou, Christina and Turner-Evans, Dan and Ribeiro, Carlos and Hermundstad, Ann M and Jayaraman, Vivek and Haberkern, Hannah} } @article {70339, title = {Reconstituting mouse embryogenesis Ex utero from Gastrulation to fetal development reveals maternally independent metabolic programs}, journal = {bioRxiv}, year = {2026}, month = {2026 Mar 17}, abstract = {

Mammalian development takes place inside the maternal uterus, creating technological constraints that make difficult the study of embryogenesis in live developing embryos. A central challenge for understanding the role of metabolism in mammalian development is discriminating placental and uterine-regulated signals from embryo-intrinsic processes independent of maternal influence, a process that until now has remained inseparable during gastrulation and organogenesis1{\textendash}3. Ex utero culture systems allowing continuous growth of embryos during pre-gastrulation to organogenesis4,5 offer a promising solution to this challenge. Here, we present optimized ex utero culture platforms that support faithful development of mouse embryos from gastrulation (embryonic day 6.5/7.5) through the fetal period (embryonic day \~12.5) and harnessed these platforms for dissecting metabolic transitions in vivo during embryogenesis independently of uterus and placenta. We characterized the metabolome of in utero and ex utero whole embryos, fetal organs and culture medium between embryonic days E6.5 and E12.5 by liquid chromatography mass-spectrometry (LC-MS) metabolomics, isotope tracing, and single cell transcriptomics. These datasets present a comprehensive overview of the dynamic embryonic metabolism during gastrulation and organogenesis in utero and ex utero. This analysis revealed that the midgestational metabolic switch occurring at E10.5-E11.5 is faithfully recapitulated ex utero, indicating that this transition is intrinsically programmed in embryonic tissues and does not require direct maternal or placental cues. Notably, oxygen availability modulated the extent of this transition, but elevated oxygen was insufficient to induce it prematurely, demonstrating that the switch is developmentally timed and only partially environmental-responsive. We further harnessed the ex utero platform for identifying and perturbing a mitochondrial redox shift at E7.5-E8.5 that is critical for developmental progress after gastrulation. These findings uncover the remarkable metabolic plasticity of the mammalian embryo, demonstrating its capacity to sustain growth independently of maternal inputs from the establishment of the body plan through the onset of the fetal period. Moreover, they highlight the use of long-term ex utero culture as a unique framework for dissecting the mechanisms that shape embryogenesis under physiological and experimentally perturbed conditions, while functionally uncoupling embryonic programs from maternal and placental influences.

}, doi = {10.64898/2026.03.17.710314}, url = {https://www.biorxiv.org/content/early/2026/03/18/2026.03.17.710314}, author = {Lokshtanov, Dmitry and Gao, Shihong Max and Xu, Weizhi and Kosman, Avraham and Roncato, Francesco and De La Cruz, Nancy and Khan, Nawal A. and Woods, Andrea and Campbell, Ian and Woehler, Andrew and Christoforou, Christina and Ding, Lang and Hu, Amy and Copeland, Monique and Wang, Lihua and Yang, Xiushuai and Raley, Castle and Delventhal, Kym M. and Herrera, Antonio and Valente, Alessandro and Wright, Sylvia and Gomez-Cesar, Elidet and Shlomo, Raanan and Golenchenko, Sergey and Oldak, Bernardo and Yilmaz, Alperen and Gurhan-Sebinc, Gulben and Comar, Mehmet-Yunus and Viukov, Sergey and Novershtern, Noa and Zhang, Hua and Duong, Thao and Li, Lingjun and Khatib, Nizar and Kakun, Reli Rachel and Espinosa-Medina, Isabel and Florian-Rodriguez, Maria E. and LaManno, Gioele and Tillberg, Paul W. and Wang, Meng C. and Maza, Itay and Srivatsan, Sanjay and Solmonson, Ashley and Hanna, Jacob H. and Aguilera-Castrejon, Alejandro} } @article {69301, title = {Motor neurons generate pose-targeted movements via proprioceptive sculpting.}, journal = {Nature}, year = {2024}, month = {2024 Mar 20}, abstract = {

Motor neurons are the final common pathway through which the brain controls movement of the body, forming the basic elements from which all movement is composed. Yet how a single motor neuron contributes to control during natural movement remains unclear. Here we anatomically and functionally characterize the individual roles of the motor neurons that control head movement in the fly, Drosophila melanogaster. Counterintuitively, we find that activity in a single motor neuron rotates the head in different directions, depending on the starting posture of the head, such that the head converges towards a pose determined by the identity of the stimulated motor neuron. A feedback model predicts that this convergent behaviour results from motor neuron drive interacting with proprioceptive feedback. We identify and genetically suppress a single class of proprioceptive neuron that changes the motor neuron-induced convergence as predicted by the feedback model. These data suggest a framework for how the brain controls movements: instead of directly generating movement in a given direction by activating a fixed set of motor neurons, the brain controls movements by adding bias to a continuing proprioceptive-motor loop.

}, issn = {1476-4687}, doi = {10.1038/s41586-024-07222-5}, author = {Gorko, Benjamin and Siwanowicz, Igor and Close, Kari and Christoforou, Christina and Hibbard, Karen L and Kabra, Mayank and Lee, Allen and Park, Jin-Yong and Li, Si Ying and Chen, Alex B and Namiki, Shigehiro and Chen, Chenghao and Tuthill, John C and Bock, Davi D and Rouault, Herv{\'e} and Branson, Kristin and Ihrke, Gudrun and Huston, Stephen J} } @article {64933, title = {Neurogenetic dissection of the lateral horn reveals major outputs, diverse behavioural functions, and interactions with the mushroom body.}, journal = {Elife}, volume = {8}, year = {2019}, month = {2019 May 21}, abstract = {

Animals exhibit innate behaviours to a variety of sensory stimuli including olfactory cues. In , one higher olfactory centre, the lateral horn (LH), is implicated in innate behaviour. However, our structural and functional understanding of the LH is scant, in large part due to a lack of sparse neurogenetic tools for this region. We generate a collection of split-GAL4 driver lines providing genetic access to 82 LH cell types. We use these to create an anatomical and neurotransmitter map of the LH and link this to EM connectomics data. We find ~30\% of LH projections converge with outputs from the mushroom body, site of olfactory learning and memory. Using optogenetic activation, we identify LH cell types that drive changes in valence behavior or specific locomotor programs. In summary, we have generated a resource for manipulating and mapping LH neurons, providing new insights into the circuit basis of innate and learned olfactory behavior.

}, issn = {2050-084X}, doi = {10.7554/eLife.43079}, author = {Dolan, Michael-John and Frechter, Shahar and Bates, Alexander Shakeel and Dan, Chuntao and Huoviala, Paavo and Roberts, Ruair{\'\i} Jv and Schlegel, Philipp and Dhawan, Serene and Tabano, Remy and Dionne, Heather and Christoforou, Christina and Close, Kari and Sutcliffe, Ben and Giuliani, Bianca and Li, Feng and Costa, Marta and Ihrke, Gudrun and Meissner, Geoffrey Wilson and Bock, Davi D and Aso, Yoshinori and Rubin, Gerald M and Jefferis, Gregory Sxe} } @article {65227, title = {Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics.}, journal = {eLife}, volume = {8}, year = {2019}, month = {2019 Nov 14}, abstract = {

Animals employ diverse learning rules and synaptic plasticity dynamics to record temporal and statistical information about the world. However, the molecular mechanisms underlying this diversity are poorly understood. The anatomically defined compartments of the insect mushroom body function as parallel units of associative learning, with different learning rates, memory decay dynamics and flexibility (Aso \& Rubin 2016). Here we show that nitric oxide (NO) acts as a neurotransmitter in a subset of dopaminergic neurons in . NO{\textquoteright}s effects develop more slowly than those of dopamine and depend on soluble guanylate cyclase in postsynaptic Kenyon cells. NO acts antagonistically to dopamine; it shortens memory retention and facilitates the rapid updating of memories. The interplay of NO and dopamine enables memories stored in local domains along Kenyon cell axons to be specialized for predicting the value of odors based only on recent events. Our results provide key mechanistic insights into how diverse memory dynamics are established in parallel memory systems.

}, issn = {2050-084X}, doi = {10.7554/eLife.49257}, author = {Aso, Yoshinori and Ray, Robert P and Long, Xi and Bushey, Daniel and Cichewicz, Karol and Ngo, Teri-Tb and Sharp, Brandi and Christoforou, Christina and Hu, Amy and Lemire, Andrew L and Tillberg, Paul and Hirsh, Jay and Litwin-Kumar, Ashok and Rubin, Gerald M} }