bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.01.24.577143

The voltage-gated potassium channel Shal (Kv4) contributes to active hearing in Drosophila

Abstract

The full complement of ion channels which influence insect auditory mechanotransduction, and the mechanisms by which their influence is exerted, remain unclear. Shal (Kv4), a Shaker family member encoding voltage-gated potassium channels in Drosophila melanogaster, has been shown to localize to dendrites in some neuron types, suggesting a potential role for Shal in Drosophila hearing, including mechanotransduction. A GFP-protein trap was used to visualize the localization of the Shal channel in Johnstons organ neurons responsible for hearing in the antenna. Shal protein was localized to the cell body and the proximal dendrite region of sensory neurons, suggesting its involvement not only in general auditory function, but specifically in mechanotransduction. Electrophysiological recordings conducted to assess neural responses to auditory stimuli in mutant Shal flies revealed significant decreases in auditory responses. Laser Doppler Vibrometer recordings indicated abnormal antennal free fluctuation frequencies in mutant lines, indicating an effect on active antennal tuning, and thus active transduction mechanisms. This suggests that Shal participates in coordinating energy-dependent antennal movements in Drosophila that are essential for tuning the antenna to courtship song frequencies. Significance StatementThe study of fruit fly hearing has revealed mechanosensitive ion channels that participate in mechanotransduction, and as in mammalian hearing, energy-dependent mechanisms actively amplify and tune auditory processes. Identifying distinct roles played by different ion channels is essential to better understand this process. Here, we explore the influence of a specific voltage-gated potassium channel, Shal, on fly hearing, and find that it affects specific parts of the mechanotransduction process. Our research uncovers Shals localization in sensory dendrite regions of auditory neurons, where it contributes to shaping mechanotransduction and active antennal tuning. Understanding Shals involvement in auditory function and mechanotransduction deepens our knowledge of fly hearing and unveils a key player in the coordination of energy-dependent active antennal movements.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Gregory, E. S., Xu, Y. Y. J., Lee, T.-T., Joiner, M.-l. A., Kamikouchi, A., Su, M. P., Eberl, D. F.. 2024-01-25. The voltage-gated potassium channel Shal (Kv4) contributes to active hearing in Drosophila. https://doi.org/10.1101/2024.01.24.577143

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↗