Advances in fluorescence microscopy enable monitoring larger brain areas in-vivo with finer time resolution. The resulting data rates require reproducible analysis pipelines that are reliable, fully automated, and scalable to datasets generated over the course of months. We present CaImAn, an open-source library for calcium imaging data analysis. CaImAn provides automatic and scalable methods to address problems common to pre-processing, including motion correction, neural activity identification, and registration across different sessions of data collection. It does this while requiring minimal user intervention, with good scalability on computers ranging from laptops to high-performance computing clusters. CaImAn is suitable for two-photon and one-photon imaging, and also enables real-time analysis on streaming data. To benchmark the performance of CaImAn we collected and combined a corpus of manual annotations from multiple labelers on nine mouse two-photon datasets. We demonstrate that CaImAn achieves near-human performance in detecting locations of active neurons.

Fractal analysis methods are used to quantify the complexity of the human cerebral cortex. Many recent studies have focused on high resolution three-dimensional reconstructions of either the outer (pial) surface of the brain or the junction between the grey and white matter, but ignore the structure between these surfaces. This study uses a new method to incorporate the entire cortical thickness. Data were obtained from the Alzheimer's Disease (AD) Neuroimaging Initiative database (Control N=35, Mild AD N=35). Image segmentation was performed using a semi-automated analysis program. The fractal dimensions of three cortical models (the pial surface, grey/white surface and entire cortical ribbon) were calculated using a custom cube-counting triangle-intersection algorithm. The fractal dimension of the cortical ribbon showed highly significant differences between control and AD subjects (p<0.001). The inner surface analysis also found smaller but significant differences (p< 0.05). The pial surface dimensionality was not significantly different between the two groups. All three models had a significant positive correlation with the cortical gyrification index (r > 0.55, p<0.001). Only the cortical ribbon had a significant correlation with cortical thickness (r = 0.832, p< 0.001) and the Alzheimer's Disease Assessment Scale cognitive battery (r = −0.513, p = 0.002). The cortical ribbon dimensionality showed a larger effect size (d=1.12) in separating control and mild AD subjects than cortical thickness (d=1.01) or gyrification index (d=0.84). The methodological change shown in this paper may allow for further clinical application of cortical fractal dimension as a biomarker for structural changes that accrue with neurodegenerative diseases.

The ventral hippocampus (vHPC) is a critical hub in networks that process emotional information. While recent studies have indicated that ventral CA1 (vCA1) projection neurons are functionally dissociable, the basic principles of how the inputs and outputs of vCA1 are organized remain unclear. Here we used viral and sequencing approaches to define the logic of the extended vCA1 circuit. Using high-throughput sequencing of genetically barcoded neurons (MAPseq) to map the axonal projections of thousands of vCA1 neurons, we identify a population of neurons that simultaneously broadcast information to multiple areas known to regulate the stress axis and approach/avoidance behavior. Through molecular profiling and viral input-output tracing of vCA1 projection neurons, we show how neurons with distinct projection targets may differ in their inputs and transcriptional signatures. These studies reveal novel organizational principles of the vHPC that may underlie its functional heterogeneity.

The enantioselective synthesis of the eunicellin ophirin B has been completed. A ring-closing metathesis provides efficient access to the oxonene ring, and a highly diastereoselective intramolecular Diels-Alder reaction results in the formation of the hydrobenzofuran portion of the molecule.

Within the cervical and lumbar spinal enlargements, central pattern generating (CPG) circuitry produces the rhythmic output necessary for limb coordination during locomotion. Long propriospinal neurons that inter-connect these CPGs are thought to secure hindlimb-forelimb coordination, ensuring that diagonal limb pairs move synchronously while the ipsilateral limb pairs move out-of-phase during stepping. Here, we show that silencing long ascending propriospinal neurons (LAPNs) that interconnect the lumbar and cervical CPGs disrupts left-right limb coupling of each limb pair in the adult rat during overground locomotion on a high-friction surface. These perturbations occurred independent of the locomotor rhythm, intralimb coordination, and speed-dependent (or any other) principal features of locomotion. Strikingly, the functional consequences of silencing LAPNs are highly context-dependent; the phenotype was not expressed during swimming, treadmill stepping, exploratory locomotion, or walking on an uncoated, slick surface. These data reveal surprising flexibility and context-dependence in the control of interlimb coordination during locomotion.