Explore the vast range of titles available.

Neurons utilize plasticity of dendritic arbors as part of a larger suite of adaptive plasticity mechanisms. This explicitly manifests with motoneurons in the Drosophila embryo and larva, where dendritic arbors are exclusively postsynaptic and are used as homeostatic devices, compensating for changes in synaptic input through adapting their growth and connectivity. We recently identified reactive oxygen species (ROS) as novel plasticity signals instrumental in this form of dendritic adjustment. ROS correlate with levels of neuronal activity and negatively regulate dendritic arbor size. Here, we investigated NADPH oxidases as potential sources of such activity-regulated ROS and implicate Dual Oxidase (but not Nox), which generates hydrogen peroxide extracellularly. We further show that the aquaporins Bib and Drip, but not Prip, are required for activity-regulated ROS-mediated adjustments of dendritic arbor size in motoneurons. These results suggest a model whereby neuronal activity leads to activation of the NADPH oxidase Dual Oxidase, which generates hydrogen peroxide at the extracellular face; aquaporins might then act as conduits that are necessary for these extracellular ROS to be channeled back into the cell where they negatively regulate dendritic arbor size.

Mapping neural circuits can be accomplished by labeling a small number of neural structures per brain, and then combining these structures across multiple brains. This sparse labeling method has been particularly effective in Drosophila melanogaster, where clonally related clusters of neurons derived from the same neural stem cell (neuroblast clones) are functionally related and morphologically highly stereotyped across animals. However identifying these neuroblast clones (approximately 180 per central brain hemisphere) manually remains challenging and time consuming. Here, we take advantage of the stereotyped nature of neural circuits in Drosophila to identify clones automatically, requiring manual annotation of only an initial, smaller set of images. Our procedure depends on registration of all images to a common template in conjunction with an image processing pipeline that accentuates and segments neural projections and cell bodies. We then measure how much information the presence of a cell body or projection at a particular location provides about the presence of each clone. This allows us to select a highly informative set of neuronal features as a template that can be used to detect the presence of clones in novel images. The approach is not limited to a specific labeling strategy and can be used to identify partial (e.g., individual neurons) as well as complete matches. Furthermore this approach could be generalized to studies of neural circuits in other organisms.

Neural circuit mapping is generating datasets of 10,000s of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches. We validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and unreported topographical features. Fully automated clustering organized the validation dataset into 1052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types including searching neurons against transgene expression patterns. Finally we show that NBLAST is effective with data from other invertebrates and zebrafish.

In many brain areas, neuronal activity is associated with a variety of behavioral and environmental variables. In particular, neuronal responses in the zebrafish hindbrain relate to oculomotor and swimming variables, as well as sensory information. However, the precise functional organization of the neurons has been difficult to unravel since neuronal responses are heterogeneous. Here we used dimensionality reduction methods on neuronal population data to reveal the role of the hindbrain in visually-driven oculomotor behavior and swimming. We imaged neuronal activity in zebrafish expressing GCaMP6s in the nucleus of almost all neurons, while monitoring the behavioral response to gratings that rotated with different speeds. We then used reduced-rank regression, a method that condenses the sensory and motor variables into a smaller number of ′features′, to predict the fluorescence traces of all ROIs (regions of interest). Despite the potential complexity of the visuo-motor transformation, our analysis revealed that the bulk of population activity can be explained by only two features. Based on the contribution of these features to each ROI′s activity, ROIs formed three clusters. One cluster was related to vergent movements and swimming, whereas the other two clusters related to leftward and rightward rotation. Voxels corresponding to these clusters were segregated anatomically, with leftward and rightward rotation clusters located selectively to the left and right hemispheres, respectively. Just as described in many cortical areas, our analysis revealed that single neuron complexity co-exists with a simpler population-level description, thereby providing insights into the organization of visuo-motor transformations in the hindbrain.Competing Interest StatementThe authors have declared no competing interest.

From lamprey to monkeys, the organization of the descending control of locomotion is conserved across vertebrates. Reticulospinal neurons (RSNs) form a bottleneck for descending commands, receiving innervation from diencephalic and mesencephalic locomotor centres and providing locomotor drive to spinal motor circuits. Given their optical accessibility in early development, larval zebrafish offer a unique opportunity to study reticulospinal circuitry. In fish, RSNs are a small, highly stereotyped, uniquely identifiable group of large neurons spanning from the midbrain to the medulla. Classically labelled by tracer dye injections into the spinal cord, recent advances in genetic tools have facilitated the targeted expression of transgenes in diverse brainstem neurons of larval zebrafish. Here, we provide a comparative characterization of four existing and three newly established transgenic lines in larval zebrafish. We determine which identified neurons are consistently labelled and offer projection-specific genetic access to subpopulations of RSNs. We showcase transgenic lines that label most or all RSNs (nefma, adcyap1bccu96Et) or subsets of RSNs, including ipsilateral (vsx2, calcaccu75Et), contralateral (pcp4accu97Tg) or all (tiam2ay264Et) components of the Mauthner array, or midbrain-only RSNs (s1171tEt). In addition to RSNs, selected transgenic lines (nefma, s1171tEt, calcaccu75Et) labelled other potential neurons of interest in the brainstem. For those, we performed in situ hybridisation to show expression patterns of several excitatory and inhibitory neurotransmitters at larval stages as well as glutamatergic expression patterns in juvenile fish. We provide an overview of transgene expression in the brainstem of larval zebrafish that serves to lay a foundation for future studies in the supraspinal control of locomotion.Competing Interest StatementThe authors have declared no competing interest.