Biology subjects

Berger, A. B.

Publications and source records attributed to Berger, A. B..

4 recordsLinked to original sources

bioRxiv2023

Neural correlates of future volitional action in Drosophila

The ability to act voluntarily is fundamental to animal behavior1,2,3,4,5. For example, self-directed movements are critical to exploration, particularly in the absence of external sensory signals that could shape a trajectory. However, how neural networks might plan future changes in direction in the absence of salient sensory cues is unknown. Here we use volumetric two-photon imaging to map neural activity associated with walking across the entire brain of the fruit fly Drosophila, register these signals across animals with micron precision, and generate a dataset of [~]20 billion neural measurements across thousands of bouts of voluntary movements. We define spatially clustered neural signals selectively associated with changes in forward and angular velocity, and reveal that turning is associated with widespread asymmetric activity between brain hemispheres. Strikingly, this asymmetry in interhemispheric dynamics emerges more than 10 seconds before a turn within a specific brain region associated with motor control, the Inferior Posterior Slope (IPS). This early, local difference in neural activity predicts the direction of future turns on a trial-by-trial basis, revealing long-term motor planning. As the direction of each turn is neither trained, nor guided by external sensory cues, it must be internally determined. We therefore propose that this pre-motor center contains a neural substrate of volitional action.

neuroscience↗

bioRxiv2023

BIFROST: a method for registering diverse imagingdatasets

The heterogeneity of brain imaging methods in neuroscience provides rich data that cannot be captured by a single technique, and our interpretations benefit from approaches that enable easy comparison both within and across different data types. For example, comparing brain-wide neural dynamics across experiments and aligning such data to anatomical resources, such as gene expression patterns or connectomes, requires precise alignment to a common set of anatomical coordinates. However, this is challenging because registering in vivo functional imaging data to ex vivo reference atlases requires accommodating differences in imaging modality, microscope specification, and sample preparation. We overcome these challenges in Drosophila by building an in vivo reference atlas from multiphoton-imaged brains, called the Functional Drosophila Atlas (FDA). We then develop a two-step pipeline, BrIdge For Registering Over Statistical Templates (BIFROST), for transforming neural imaging data into this common space and for importing ex vivo resources such as connectomes. Using genetically labeled cell types as ground truth, we demonstrate registration with a precision of less than 10 microns. Overall, BIFROST provides a pipeline for registering functional imaging datasets in the fly, both within and across experiments. SignificanceLarge-scale functional imaging experiments in Drosophila have given us new insights into neural activity in various sensory and behavioral contexts. However, precisely registering volumetric images from different studies has proven challenging, limiting quantitative comparisons of data across experiments. Here, we address this limitation by developing BIFROST, a registration pipeline robust to differences across experimental setups and datasets. We benchmark this pipeline by genetically labeling cell types in the fly brain and demonstrate sub-10 micron registration precision, both across specimens and across laboratories. We further demonstrate accurate registration between in-vivo brain volumes and ultrastructural connectomes, enabling direct structure-function comparisons in future experiments.

neuroscience↗

bioRxiv2022

Mapping the Neural Dynamics of Locomotion across the Drosophila Brain

Walking is a fundamental mode of locomotion, yet its neural correlates are unknown at brain-wide scale in any animal. We use volumetric two-photon imaging to map neural activity associated with walking across the entire brain of Drosophila. We detect locomotor signals in approximately 40% of the brain, identify a global signal associated with the transition from rest to walking, and define clustered neural signals selectively associated with changes in forward or angular velocity. These networks span functionally diverse brain regions, and include regions that have not been previously linked to locomotion. We also identify time-varying trajectories of neural activity that anticipate future movements, and that represent sequential engagement of clusters of neurons with different behavioral selectivity. These motor maps suggest a dynamical systems framework for constructing walking maneuvers reminiscent of models of forelimb reaching in primates and set a foundation for understanding how local circuits interact across large-scale networks.

neuroscience↗

bioRxiv2022

Glial control of sphingolipid levels sculpts diurnal remodeling of sleep circuitry

Structural plasticity in the brain often necessitates dramatic remodeling of neuronal processes and attendant reorganization of the cytoskeleton and membranes. While cytoskeletal restructuring has been studied extensively, how lipids might orchestrate structural plasticity remains unclear. We show that specific glial cells in Drosophila produce Glucocerebrosidase (GBA) to locally catabolize sphingolipids. Sphingolipid accumulation drives lysosomal dysfunction, causing gba1b mutants to harbor protein aggregates that cycle across circadian time and are regulated by neural activity, the circadian clock, and sleep. While the vast majority of membrane lipids are stable across the day, a specific subset, highly enriched in sphingolipids, cycles daily in a gba1b-dependant fashion. In parallel, circadian clock neurons remodel their neurites, growing and shrinking across the day to shape circadian behavior. Remarkably, this neuronal remodeling relies on a cycle of temporally offset sphingolipid biosynthesis and catabolism. Thus, dynamic sphingolipid regulation by glia enables diurnal circuit remodeling and proper circadian behavior.

neuroscience↗