Biology subjects

Schneider, M. W.

Publications and source records attributed to Schneider, M. W..

4 recordsLinked to original sources

bioRxiv2024

Positional information drives distinct traits in transcriptomically identified neuronal types

Neuronal phenotypic traits such as morphology, connectivity, and function are dictated, to a large extent, by a specific combination of differentially expressed genes. Clusters of neurons in transcriptomic space correspond to distinct cell types and in some cases (e. g., C. elegans neurons1 and retinal ganglion cells2-4) have been shown to share morphology and function. The zebrafish optic tectum is composed of a spatial array of neurons that transforms visual inputs into motor outputs. While the visuotopic map is continuous, subregions of the tectum are functionally specialized5,6. To uncover the cell-type architecture of the tectum, we transcriptionally profiled its neurons, revealing more than 60 cell types that are organized in distinct anatomical layers. We then measured the visual responses of thousands of tectal neurons by two-photon calcium imaging and matched them with their transcriptional profile. Furthermore, we characterized the morphologies of transcriptionally identified neurons using specific transgenic lines. Surprisingly, we found that neurons that are transcriptionally similar can diverge functionally and morphologically. Incorporating the spatial coordinates of neurons within the tectal volume revealed functionally and morphologically defined anatomical subclusters within individual transcriptomic clusters. Our findings demonstrate that extrinsic, position-dependent factors expand the phenotypic repertoire of genetically similar neurons.

neuroscience↗

bioRxiv2023

Diverse prey capture strategies in teleost larvae

Animal behavior is adapted to the sensory environment in which it evolved, while also being constrained by physical limits, evolutionary history, and developmental trajectories. The hunting behavior of larval zebrafish (Danio rerio), a cyprinid native to streams in Eastern India, has been well characterized. However, it is unknown if the complement and sequence of movements employed during prey capture by zebrafish is universal across freshwater teleosts. Here, we explore the syntax of prey capture behavior in larval fish belonging to the clade Percomorpha, whose last common ancestor with cyprinids lived [~]240 million years ago. We compared the behavior of four cichlid species from Lake Tanganyika endemic to deep benthic parts of the lake (Lepidiolamprologus attenuatus, Lamprologus ocellatus, and Neolamprologus multifasciatus) or inhabiting rivers (Astatotilapia burtoni) with that of medaka (Oryzias latipes), a fish found in rice paddies in East Asia. Using high speed videography and neural networks, we tracked eye movements and extracted swim kinematics during hunting from larvae of these five species. Notably, we found that the repertoire of hunting movements of cichlids is broader than that of zebrafish, but shares basic features, such as eye convergence, positioning of prey centrally in the binocular visual field, and discrete prey capture bouts, including two kinds of capture strikes. In contrast, medaka swim continuously, track the prey monocularly without eye convergence, and position prey laterally before capturing them with a side swing. This configuration of kinematic motifs suggests that medaka may judge distance to prey predominantly by motion parallax, while cichlids and zebrafish may mainly use binocular visual cues. Together, our study documents the diversification of locomotor and oculomotor adaptations among hunting teleost larvae.

animal behavior and cognition↗

bioRxiv2021

RIM and RIM-binding protein localize synaptic Cav2 channels in a differential manner to regulate transmission in neuronal circuits

At chemical synapses, voltage-gated Ca2+-channels (VGCCs) translate electrical signals into a trigger for synaptic vesicle (SV) fusion. VGCCs and the Ca2+ microdomains they elicit must be located precisely to primed SVs, to evoke rapid transmitter release. Localization is mediated by Rab3 interacting molecule (RIM) and RIM-binding proteins (RIM-BPs), which interact and bind to the C-terminus of the CaV2 VGCC -subunit. We studied this machinery at the mixed cholinergic/GABAergic neuromuscular junction (NMJ) of Caenorhabditis elegans. rimb-1 mutants had mild synaptic defects, through loosening the anchoring of UNC-2/CaV2 and delaying the onset of SV fusion. UNC-10/RIM deletion much more severely affected transmission. Even though postsynaptic depolarization was reduced, rimb-1 mutants had increased cholinergic (but reduced GABAergic) transmission, to compensate for the delayed release. This did not occur when the excitation-inhibition balance was altered by removing GABA transmission. RIMB-1 thus may differentially regulate transmission in mixed circuits. Untethering the UNC-2/CaV2 channel by removing its C-terminal PDZ ligand exacerbated the rimb-1 defects, and similar phenotypes resulted from acute degradation of the CaV2 {beta}-subunit CCB-1. Therefore, untethering of the CaV2 complex is as severe as its elimination, yet does not abolish transmission, likely due to compensation by CaV1. Thus, robustness and flexibility of synaptic transmission emerges from VGCC regulation.

neuroscience↗

bioRxiv2016

BLISS: quantitative and versatile genome-wide profiling of DNA breaks in situ

We present a method for genome-wide DNA double-strand Breaks (DSBs) Labeling In Situ and Sequencing (BLISS) which, compared to existing methods, introduces several key features: 1) high efficiency and low input requirement by in situ DSB labeling in cells or tissue sections directly on a solid surface; 2) easy scalability by performing in situ reactions in multi-well plates; 3) high sensitivity by linearly amplifying tagged DSBs using in vitro transcription; and 4) accurate DSB quantification and control of PCR biases by using unique molecular identifiers. We demonstrate the ability to use BLISS to quantify natural and drug-induced DSBs in low-input samples of cancer cells, primary mouse embryonic stem cells, and mouse liver tissue sections. Finally, we applied BLISS to compare the specificity of CRISPR-associated RNA-guided endonucleases Cas9 and Cpf1, and found that Cpf1 has higher specificity than Cas9. These results establish BLISS as a versatile, sensitive, and efficient method for genome-wide DSB mapping in many applications.

molecular biology↗