Biology subjects

Aakhte, M.

Publications and source records attributed to Aakhte, M..

5 recordsLinked to original sources

bioRxiv2026

Multichannel optical cochlear implants enable spectrally distinct auditory activity

When hearing fails, cochlear implants (CIs) restore auditory perception. Yet, coding of spectral information remains a bottleneck because each electrode broadly activates the auditory nerve. As light can be more conveniently confined, optical (o)CIs present an alternative. Here, we combined expression of the potent channelrhodopsin ChReef in spiral ganglion neurons (SGNs) with oCIs comprising 5-10 green LEDs in gerbils. This combination enabled systematic comparison of encoding intensity and spectral information by individual oCI channels to acoustic and electrical stimulation within a translationally feasible energy range. Recordings from the inferior colliculus (ICC) showed that ChReef aligned SGN light sensitivity with LED radiant fluxes: ICC activity had thresholds <200 nJ and reached a maximum equivalent to that achieved with 51 dB SPL pure tones. Multichannel oCIs enabled tonotopically ordered, spectrally distinct stimulation that more closely resembled acoustic stimulation than did electrical stimulation. Some LEDs elicited multiple spectral peaks at higher intensities. Linear discriminant analysis of ICC activity indicated improved channel discriminability for optical over electrical stimulation. In summary, ,micro-joule oCI-stimulation achieves improved spectral resolution over state-of-the-art electrical stimulation.

neuroscience↗

bioRxiv2025

CochleaNet: deep learning-based image analysis for cochlear connectomics and gene therapy

With the emergence of gene and optogenetic therapies targeting deafness, the comprehensive analysis of the molecular anatomy and physiology of the cochlea has become ever more important. Here, we introduce CochleaNet, a deep learning-based framework to analyze volumetric imaging data obtained by light-sheet microscopy of decalcified, cleared and fluorescently labeled cochleae. CochleaNet covers the workflow from reconstruction of the cochlea to segmentation of inner hair cells, spiral ganglion neurons and their afferent synapses, to analyzing the expression of gene therapy products. We validated CochleaNet by comparison to manual image analysis. Trained on high isotropic resolution mouse data, CochleaNet was also applicable to the cochlea of the gerbil, another relevant animal model, and lower-resolution mouse data from a commercially available microscope. We conclude that the combination of light-sheet microscopy and image analysis with CochleaNet paves the way for rapid and reliable quantification of cochlear molecular anatomy and preclinical gene therapy outcomes.

neuroscience↗

bioRxiv2025

Isotropic, aberration-corrected light sheet microscopy for rapid high-resolution imaging of cleared tissue

Light sheet microscopy is the ideal technique for multiscale imaging of large and cleared tissues, and it is desirable to achieve the highest possible isotropic resolution across the entire sample. However, isotropic resolution for a centimeter-sized sample has only been achieved with slow and often aberrated, axially scanned light sheets, resulting in a low resolution of several micrometers. Here, we introduce a compact, high-speed light sheet fluorescence microscope with isotropic sub-micron resolution optimized for cleared tissue. We introduce three major opto-mechanical innovations using off-the-shelf optics to achieve an isotropic resolution of 850 nm across samples up to 1 cm3 and refractive indices ranging from 1.33 to 1.56, using mechanical tiling with a field of view of 800 {micro}m x 800 {micro}m. We show that combining an air objective and a meniscus lens achieves an axially swept light sheet with sub-micron diffraction-limited resolution and aberration correction. The effective field of view is increased 2-fold by correcting the field curvature of the light sheet with a concave mirror in the remote focusing unit. Furthermore, the imaging speed is enhanced 10-fold by adapting the light sheets motion with a closed-loop feedback, reaching 100 frames per second while maintaining isotropic resolution across the large field of view. Finally, we showcase the performance of our light sheet system for imaging from subcellular up to centimeter scale in cleared zebrafish, mouse cochlea, and mouse brain using various clearing methods.

developmental biology↗

bioRxiv2021

Multiview tiling light sheet microscopy for 3D high resolution live imaging

Light sheet or selective plane illumination microscopy (SPIM) is ideally suited for in toto imaging of living specimens at high temporal-spatial resolution. In SPIM, the light scattering that occurs during imaging of opaque specimens brings about limitations in terms of resolution and the imaging field of view. To ameliorate this shortcoming, the illumination beam can be engineered into a highly confined light sheet over a large field of view and multi-view imaging can be performed by applying multiple lenses combined with mechanical rotation of the sample. Here, we present a Multiview tiling SPIM (MT-SPIM) that combines the Multi-view SPIM (M-SPIM) with a confined, multi-tiled light sheet. The MT-SPIM provides high-resolution, robust and rotation-free imaging of living specimens. We applied the MT-SPIM to image nuclei and Myosin II from the cellular to subcellular spatial scale in early Drosophila embryogenesis. We show that the MT-SPIM improves the axial-resolution relative to the conventional M-SPIM by a factor of two. We further demonstrate that this axial resolution enhancement improves the automated segmentation of Myosin II distribution and of nuclear volumes and shapes.

developmental biology↗

bioRxiv2018

SSPIM: a beam shaping toolbox for structured selective plane illumination microscopy

An important aim of the development of selective plane illumination microscopy (SPIM) is to present a completely open and flexible microscope set-up for nonspecialist users. Here, we report Structured SPIM (SSPIM), which provides an open-source, user-friendly and compact toolbox for beam shaping that can generate digital patterns for a wide range of illumination beams. SSPIM represents a toolbox to produce static, spherical Gaussian, Bessel and Airy beams by simple control of a Spatial Light Modulator (SLM). In addition, it is able to produce patterns for incoherent and coherent (lattice beam) array beam formation and tiling for all types of beams supported. We demonstrate the workflow and experimental and simulation results using the SSPIM toolbox. In final, the capability of the SSPIM is investigated with 3D imaging of Drosophila embryo using three different illumination beams such as scanned/dithered Gaussian, Bessel and Lattice beam which engineered with SSPIM. SSPIM toolbox is easy to use and applicable for a wide range of applications to generate and optimize the desired beam pattern and thus can help developing adaptation of the Open SPIM system towards a wider range of biological samples.

bioinformatics↗