@article {65198, title = {A bidirectional network for appetite control in larval zebrafish.}, journal = {Elife}, volume = {8}, year = {2019}, month = {2019 Oct 18}, abstract = {

Medial and lateral hypothalamic loci are known to suppress and enhance appetite, respectively, but the dynamics and functional significance of their interaction have yet to be explored. Here we report that, in larval zebrafish, primarily serotonergic neurons of the ventromedial caudal hypothalamus (cH) become increasingly active during food deprivation, whereas activity in the lateral hypothalamus (LH) is reduced. Exposure to food sensory and consummatory cues reverses the activity patterns of these two nuclei, consistent with their representation of opposing internal hunger states. Baseline activity is restored as food-deprived animals return to satiety via voracious feeding. The antagonistic relationship and functional importance of cH and LH activity patterns were confirmed by targeted stimulation and ablation of cH neurons. Collectively, the data allow us to propose a model in which these hypothalamic nuclei regulate different phases of hunger and satiety and coordinate energy balance via antagonistic control of distinct behavioral outputs.

}, issn = {2050-084X}, doi = {10.7554/eLife.43775}, author = {Wee, Caroline Lei and Song, Erin Yue and Johnson, Robert Evan and Ailani, Deepak and Randlett, Owen and Kim, Ji-Yoon and Nikitchenko, Maxim and Bahl, Armin and Yang, Chao-Tsung and Ahrens, Misha B and Kawakami, Koichi and Engert, Florian and Kunes, Sam} } @article {49520, title = {Brain-wide organization of neuronal activity and convergent sensorimotor transformations in larval zebrafish.}, journal = {Neuron}, volume = {100}, year = {2018}, month = {2018 Nov 21}, pages = {876-890.e5}, abstract = {

Simultaneous recordings of large populations of neurons in behaving animals allow detailed observation of high-dimensional, complex brain activity. However, experimental approaches often focus on singular behavioral paradigms or brain areas. Here, we recorded whole-brain neuronal activity of larval zebrafish presented with a battery of visual stimuli while recording fictive motor output. We identified neurons tuned to each stimulus type and motor output and discovered groups of neurons in the anterior hindbrain that respond to different stimuli eliciting similar behavioral responses. These convergent sensorimotor representations were only weakly correlated to instantaneous motor activity, suggesting that they critically inform, but do not directly generate, behavioral choices. To catalog brain-wide activity beyond explicit sensorimotor processing, we developed an unsupervised clustering technique that organizes neurons into functional groups. These analyses enabled a broad overview of the functional organization of the brain and revealed numerous brain nuclei whose neurons exhibit concerted activity patterns.

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2018.09.042}, author = {Chen, Xiuye and Mu, Yu and Hu, Yu and Kuan, Aaron T and Nikitchenko, Maxim and Randlett, Owen and Chen, Alex B and Gavornik, Jeffery P and Sompolinsky, Haim and Engert, Florian and Ahrens, Misha B} } @article {48497, title = {Whole-brain serial-section electron microscopy in larval zebrafish.}, journal = {Nature}, volume = {545}, year = {2017}, month = {2017 May 18}, pages = {345-349}, abstract = {

High-resolution serial-section electron microscopy (ssEM) makes it possible to investigate the dense meshwork of axons, dendrites, and synapses that form neuronal circuits. However, the imaging scale required to comprehensively reconstruct these structures is more than ten orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons, some of which span nearly the entire brain. Difficulties in generating and handling data for large volumes at nanoscale resolution have thus restricted vertebrate studies to fragments of circuits. These efforts were recently transformed by advances in computing, sample handling, and imaging techniques, but high-resolution examination of entire brains remains a challenge. Here, we present ssEM data for the complete brain of a larval zebrafish (Danio rerio) at 5.5 days post-fertilization. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management requirements. The resulting dataset can be analysed to reconstruct neuronal processes, permitting us to survey all myelinated axons (the projectome). These reconstructions enable precise investigations of neuronal morphology, which reveal remarkable bilateral symmetry in myelinated reticulospinal and lateral line afferent axons. We further set the stage for whole-brain structure-function comparisons by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. All obtained images and reconstructions are provided as an open-access resource.

}, issn = {1476-4687}, doi = {10.1038/nature22356}, author = {Hildebrand, David Grant Colburn and Cicconet, Marcelo and Torres, Russel Miguel and Choi, Woohyuk and Quan, Tran Minh and Moon, Jungmin and Wetzel, Arthur Willis and Scott Champion, Andrew and Graham, Brett Jesse and Randlett, Owen and Plummer, George Scott and Portugues, Ruben and Bianco, Isaac Henry and Saalfeld, Stephan and Baden, Alexander David and Lillaney, Kunal and Burns, Randal and Vogelstein, Joshua Tzvi and Schier, Alexander Franz and Lee, Wei-Chung Allen and Jeong, Won-Ki and Lichtman, Jeff William and Engert, Florian} } @article {47380, title = {Brain-wide mapping of neural activity controlling zebrafish exploratory locomotion.}, journal = {eLife}, year = {2016}, month = {2016 Mar 22}, abstract = {

In the absence of salient sensory cues to guide behavior, animals must still execute sequences of motor actions in order to forage and explore. How such successive motor actions are coordinated to form global locomotion trajectories is unknown. We mapped the structure of larval zebrafish swim trajectories in homogeneous environments and found that trajectories were characterized by alternating sequences of repeated turns to the left and to the right. Using whole-brain light-sheet imaging, we identified activity relating to the behavior in specific neural populations that we termed the anterior rhombencephalic turning region (ARTR). ARTR perturbations biased swim direction and reduced the dependence of turn direction on turn history, indicating that the ARTR is part of a network generating the temporal correlations in turn direction. We also find suggestive evidence for ARTR mutual inhibition and ARTR projections to premotor neurons. Finally, simulations suggest the observed turn sequences may underlie efficient exploration of local environments.

}, doi = {10.7554/eLife.12741}, url = {http://dx.doi.org/10.7554/eLife.12741}, author = {Dunn, Timothy W. and Mu, Yu and Narayan, Sujatha and Randlett, Owen and Naumann, Eva A. and Yang, Chao-Tsung and Schier, Alexander F. and Freeman, Jeremy and Engert, Florian and Ahrens, Misha B.} } @article {48388, title = {Whole-brain activity mapping onto a zebrafish brain atlas.}, journal = {Nature methods}, volume = {12}, year = {2015}, month = {2015 Nov}, pages = {1039-46}, abstract = {

In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open-source atlas containing molecular labels and definitions of anatomical regions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated extracellular signal{\textendash}regulated kinase (ERK) as a readout of neural activity, we have developed a system to create and contextualize whole-brain maps of stimulus- and behavior-dependent neural activity. This mitogen-activated protein kinase (MAP)-mapping assay is technically simple, and data analysis is completely automated. Because MAP-mapping is performed on freely swimming fish, it is applicable to studies of nearly any stimulus or behavior. Here we demonstrate our high-throughput approach using pharmacological, visual and noxious stimuli, as well as hunting and feeding. The resultant maps outline hundreds of areas associated with behaviors.

}, keywords = {Algorithms, Animals, Automation, Behavior, Animal, Brain, Brain Mapping, Calcium, Extracellular Signal-Regulated MAP Kinases, Image Processing, Computer-Assisted, Immunohistochemistry, Microscopy, Confocal, Neurites, Neurons, Phosphorylation, Principal Component Analysis, Reproducibility of Results, Software, Swimming, Zebrafish}, issn = {1548-7105}, doi = {10.1038/nmeth.3581}, author = {Randlett, Owen and Wee, Caroline L and Naumann, Eva A and Nnaemeka, Onyeka and Schoppik, David and Fitzgerald, James E and Portugues, Ruben and Lacoste, Alix M B and Riegler, Clemens and Engert, Florian and Schier, Alexander F} }