bioRxiv ScienceSearch

bioRxiv · 10.1101/244434

Functionally asymmetric motor neurons coordinate locomotion of Caenorhabditis elegans

Abstract

Invertebrate nervous systems are valuable models for fundamental principles of the control of behavior. Ventral nerve cord (VNC) motor neurons in Caenorhabditis elegans represent one of the best studied locomotor circuits, with known connectivity and functional information about most of the involved neuron classes. However, for one of those, the AS motor neurons (AS MNs), no physiological data is available. Combining specific expression and selective illumination, we precisely targeted AS MNs by optogenetics and addressed their role in the locomotion circuit. After photostimulation, AS MNs induce currents in post-synaptic body wall muscles (BWMs), exhibiting an initial asymmetry of excitatory output. This may facilitate complex regulatory motifs for adjusting direction during navigation. By behavioral and photo-inhibition experiments, we show that AS MNs contribute to propagation of the antero-posterior body wave during locomotion. By Ca2+-imaging in AS MNs and in their synaptic partners, we also reveal that AS MNs play a role in mediating forward and backward locomotion by integrating activity of premotor interneurons (PINs), as well as in coordination of the dorso-ventral body wave. AS MNs do not exhibit pacemaker properties, but potentially gate VNC central pattern generators (CPGs), as indicated by ceasing of locomotion when AS MNs are hyperpolarized. AS MNs provide positive feedback to the PIN AVA via gap junctions, a feature found also in other locomotion circuits. In sum, AS MNs have essential roles in coordinating locomotion, combining several functions, and emphasizing the compressed nature of the C. elegans nervous system in comparison to higher animals.\n\nHighlightsA class of motor neurons with unidentified function - AS cholinergic motor neurons - was characterized in C. elegans.\n\nAS neurons show asymmetry in both input and output and are specialized in coordination of dorso-ventral undulation bends.\n\nAS neurons mediate antero-posterior propagation of the undulatory body wave during locomotion.\n\nAS neurons integrate signals for forward and reverse locomotion from premotor interneurons and may gate ventral nerve cord central pattern generators (CPGs) via gap junctions.

Source connections

Explore related subjects

Keep this discovery

BibTeXRIS

Tolstenkov, O., Van der Auwera, P., Liewald, J. F., Steuer Costa, W., Bazhanova, O., Gemeinhardt, T. M., Bergs, A. C. F., Gottschalk, A.. 2018-01-10. Functionally asymmetric motor neurons coordinate locomotion of Caenorhabditis elegans. https://doi.org/10.1101/244434

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience