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Woo, S. J.

Publications and source records attributed to Woo, S. J..

3 recordsLinked to original sources

Extracting task-relevant preserved dynamics from contrastive aligned neural recordings

Recent work indicates that low-dimensional dynamics of neural and behavioral data are often preserved across days and subjects. However, extracting these preserved dynamics remains challenging: high-dimensional neural population activity and the recorded neuron populations vary across recording sessions. While existing modeling tools can improve alignment between neural and behavioral data, they often operate on a per-subject basis or discretize behavior into categories, disrupting its natural continuity and failing to capture the underlying dynamics. We introduce Contrastive Aligned Neural DYnamics (CANDY), an end-to-end framework that aligns neural and behavioral data using rank-based contrastive learning, adapted for continuous behavioral variables, to project neural activity from different sessions onto a shared low-dimensional embedding space. CANDY fits a shared linear dynamical system to the aligned embeddings, enabling an interpretable model of the conserved temporal structure in the latent space. We validate CANDY on synthetic and real-world datasets spanning multiple species, behaviors, and recording modalities. Our results show that CANDY is able to learn aligned latent embeddings and preserved dynamics across neural recording sessions and subjects, and it achieves improved cross-session behavior decoding performance. We further show that the latent linear dynamical system generalizes to new sessions and subjects, achieving comparable or even superior behavior decoding performance to models trained from scratch. These advances enable robust cross-session behavioral decoding and offer a path towards identifying shared neural dynamics that underlie behavior across individuals and recording conditions. The code and two-photon imaging data of striatal neural activity that we acquired here are available at https://github.com/schnitzer-lab/CANDY-public.git.

neuroscience↗

Super Recombinator (SuRe): An in vivo recombination system for scalable and efficient transgene assembly at a single genomic locus

The capacity to engineer organisms with multiple transgenic components is crucial to synthetic biology and basic biology research. For the former field, transgenic organisms allow the creation of novel biological functions; for the latter, such organisms provide potent means of dissecting complex biological pathways. However, the size limitations of a single transgenesis event and challenges associated with the assembly of multiple DNA fragments hinder the efficient integration of multiple transgenes. To overcome these hurdles, here we introduce a building block for synthetic design termed an integrated genetic array (IGA), which incorporates all genetic components into a single locus to prevent their separation during genetic manipulations. Since the natural recombination rate for genes located in the same locus is near zero, to construct IGAs we developed the Super Recombinator (SuRe) system, which uses CRISPR/Cas9, alone or in combination with site-specific serine recombinases, for in vivo transgene recombination at a single genomic locus. SuRe effectively doubles the number of elements assembled in each recombination round, exponentially accelerating IGA construction. By preventing the separation of transgenic elements, SuRe greatly reduces screening burdens, as validated here through studies of Drosophila melanogaster and Caenorhabditis elegans. To optimize SuRe, we compared CRISPR/Cas9-induced homology-directed recombination to site-specific recombination using various serine recombinases. Optimized versions of SuRe achieved efficiency and fidelity values near their theoretical maxima and allowed the generation of recombinant products up to 4.2 Mbp in size in Drosophila. Using SuRe, we created fruit flies with 12 transgenic elements for fluorescence voltage imaging of neural activity in precisely defined cell-types. Mathematical modeling of the scalability of SuRe to large transgene assemblies showed that integration times and gene assembly workloads respectively scale logarithmically and linearly with the number of transgenes, both major improvements over conventional approaches. Overall, SuRe enables the efficient integration of multiple genes at individual loci, up to the chromosomal scale.

synthetic biology↗

An autonomous robotic system for high-throughput phenotyping and behavioral studies of individual fruit flies

The fruit fly, Drosophila melanogaster, is a widely used model species in biomedical research. Despite its importance, conducting manual experiments with individual fruit flies can be challenging and time-consuming, especially for studies of individual fly behaviors. Such studies often involve cumbersome preparatory steps, such as manually tethering a fly and then positioning it within an experimental setup1,2. These procedures commonly require the fly to be anesthetized, and, before behavioral assessments begin, the fly must recover from anesthesia. Hence, the introduction of automated phenotyping and behavioral assays would expedite important aspects of fly research, by minimizing manual handling of flies and decreasing the net time needed for experiments. Here, we introduce FlyMAX (Fly Manipulation and Autonomous eXperimentation), an autonomous robotic system for manipulating adult flies without use of anesthesia. FlyMAX collects individual flies from a standard vial, analyzes them with computer vision, and achieves a throughput of >1,000 flies per day for high-throughput inspection and characterization assays. Robotic handling had no detectable adverse effects on fly longevity or our assessments of fly health. Moreover, the behavioral performance of flies, especially of males, was better and less variable than of flies handled manually. Our system employs deep learning-based machine vision for real-time assessments of picking quality and fly phenotypes. This enables fully pipelined, autonomous experimentation for behavioral assays with individual flies in controlled environments, which was previously infeasible. Overall, FlyMAX constitutes a promising technology to enhance the efficiency and reproducibility of research with flies and other insects in fields such as genetics, neuroscience, and drug screening.

neuroscience↗