Biology subjects

Samuel, A. D.

Publications and source records attributed to Samuel, A. D..

4 recordsLinked to original sources

bioRxiv2026

RAEM: random-access electron microscopy for revisitable 3D imaging

Volume electron microscopy is essential for understanding cells, tissues, and neural circuits in their native 3D context, but many biological specimens are too large to image exhaustively at nanometer resolution. Researchers therefore must choose between broad anatomical context and ultrastructural detail. We introduce random-access electron microscopy (RAEM), a framework for studying fixed tissue repeatedly across scales rather than imaging it once at a single resolution. RAEM first builds a lower resolution 3D survey of the specimen, then uses accumulated human or AI-derived knowledge of that volume to guide the microscope back to selected physical sites for high resolution imaging. By linking reconstructed 3D coordinates to precise electron-beam positions on the original sections, RAEM enables targeted imaging of membranes, vesicles, and other nanoscale structures within specimens that would be impractical to image exhaustively. We demonstrate RAEM with vesicle-resolved imaging of synaptic boutons in human cortex, targeted imaging of more than one million human cortical mitochondria, hierarchical imaging of a nematode nervous system, and retrospective targeting of a previously published petabyte-scale human cortical volume. RAEM turns serial-section EM into a query-driven, multi-resolution approach for scalable biomedical discovery.

neuroscience↗

bioRxiv2022

PEZO-1 and TRP-4 mechanosensors are involved in mating behavior in Caenorhabditis elegans

Male mating in Caenorhabditis elegans is a complex behavior with a strong mechanosensory component. C. elegans has several characterized mechanotransducer proteins, but few have been shown to contribute to mating. Here, we investigated the roles of PEZO-1, a piezo channel, and TRP-4, a mechanotransducing TRPN channel, in male mating behavior. We show that pezo-1 is expressed in several male-specific neurons with known roles in mating. We show that, among other neurons, trp-4 is expressed in the PCA sensory neuron, which monitors relative sliding between the male and the hermaphrodite and inhibits neurons involved in vulva detection. Mutations in both genes compromise many steps of mating, including initial response to the hermaphrodite, scanning, turning, and vulva detection. We performed pan-neuronal imaging during mating between freely-moving mutant males and hermaphrodites. Both pezo-1 and trp-4 mutants showed spurious activation of the sensory neurons involved in vulva detection. In trp-4 mutants, this spurious activation might be caused by PCA failure to inhibit vulva-detecting neurons during scanning. Indeed, we show that without functional TRP-4, PCA fails to detect the relative sliding between the male and hermaphrodite. Cell-specific TRP-4 expression restores PCAs mechanosensory function. Our results demonstrate new roles for both PEZO-1 and TRP-4 mechanotransducers in C. elegans mating behavior.

neuroscience↗

bioRxiv2022

Post-embryonic maturation of the C. elegans motor circuit

During development, animals can maintain behavioral output even as the underlying circuits structurally remodel. After hatching, C. elegans undergoes substantial motor neuron expansion and synapse re-wiring while the animal continuously moves with an undulatory pattern. To understand how the circuit transitions from its juvenile to mature configuration without disrupting functional output, we reconstructed the C. elegans motor circuit by electron microscopy across larval development. We observed: 1) Embryonic motor neurons transiently interact with the developing post-embryonic motor neurons prior to remodeling of their juvenile wiring; 2) Post-embryonic neurons initiate synapse development with their future partners as their neurites navigate through the juvenile nerve cords; 3) Embryonic and post-embryonic neurons sequentially build structural machinery needed for the adult circuit before the embryonic neurons relinquish their roles to post-embryonic neurons; 4) This transition is repeated region by region along the body in an anterior to posterior sequence, following the birth order of post-embryonic neurons. Through this orchestrated, programmed and gradual rewiring, the motor circuit transforms from asymmetric to symmetric wiring. These maturation strategies support the continuous maintenance of motor patterns as the juvenile circuit develops into the adult configuration. HighlightsO_LIPost-embryonic motor circuit maturation was reconstructed by synapse-resolution serial EM. C_LIO_LIMotor patterns are maintained as the circuit matures from asymmetric to symmetric configuration. C_LIO_LIProgrammed rewiring gradually and sequentially transforms the circuit structure. C_LIO_LIPreparatory and communicative wiring-rewiring allows maturation without functional disruption. C_LI

neuroscience↗

bioRxiv2019

NeuroPAL: A Neuronal Polychromatic Atlas of Landmarks for Whole-Brain Imaging in C. elegans

Comprehensively resolving single neurons and their cellular identities from whole-brain fluorescent images is a major challenge. We achieve this in C. elegans through the engineering and use of a multicolor transgene called NeuroPAL (a Neuronal Polychromatic Atlas of Landmarks). NeuroPAL worms share a stereotypical multicolor fluorescence map for the entire hermaphrodite nervous system that allows comprehensive determination of neuronal identities. Neurons labeled with NeuroPAL do not exhibit fluorescence in the green, cyan, or yellow emission channels, allowing the transgene to be used with numerous reporters of gene expression or neuronal dynamics. Here we showcase three studies that leverage NeuroPAL for nervous-system-wide neuronal identification. First, we determine the brainwide expression patterns of all metabotropic receptors for acetylcholine, GABA, and glutamate, completing a map of this communication network. Second, we uncover novel changes in cell fate caused by transcription factor mutations. Third, we record brainwide activity in response to attractive and repulsive chemosensory cues, characterizing multimodal coding and novel neuronal asymmetries for these stimuli. We present a software package that enables semi-automated determination of all neuronal identities based on color and positional information. The NeuroPAL framework and software provide a means to design landmark atlases for other tissues and organisms. In conclusion, we expect NeuroPAL to serve as an invaluable tool for gene expression analysis, neuronal fate studies, and for mapping whole-brain activity patterns.

neuroscience↗