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Fenton, G. E.

Publications and source records attributed to Fenton, G. E..

3 recordsLinked to original sources

LGR5 and SOX2 expressing progenitor cells in the adult and aged human and mouse inner ear have the potential to produce Myosin 7A positive cells in vitro

Hearing loss and deafness as a result of hair cell loss cannot be restored due to the incapacity of spontaneous regeneration of these cells. Compounds that manipulate key signaling pathways can potentially regenerate cochlear hair cells. In order to test different compounds that promote hair cell regeneration in vitro models can be used. Three-dimensional cultures have allowed the expansion and experimentation of human and mouse inner ear organoids. This is mainly performed in the embryonic or the early postnatal developmental stage. However, since the majority of patients with hearing loss are adult, it is crucial to understand the adult inner ear regenerative capacity. Here, we evaluated progenitor cell markers in the adult human and mouse inner ear and the generation, expansion and differentiation of cochlear organoids derived from the adult human and mouse inner ear. Cochlear and vestibular sensory epithelium from adult humans; and from adult and aged mice express the progenitor markers SOX2 and LGR5; and can generate organoids in vitro. By optimizing the culture conditions, organoids derived from the cochlea and vestibular organ from adult human and adult and aged mouse differentiated to Myosin 7A positive cells. This indicates that the adult inner ear has regenerative capacity. These findings are encouraging for future regenerative therapies to cure hair cell-related hearing loss and deafness.

neuroscience↗

Neuronal recordings in head-fixed and freely-moving mole-rats

Mole-rats are subterranean rodents that have evolved remarkable sensory adaptations to life in underground tunnel systems, yet their neural mechanisms remain largely unexplored. Here, we present a protocol for in vivo electrophysiological recordings in awake, head-fixed, and freely moving African mole-rats (Fukomys anselli/micklemi), overcoming unique challenges of studying the neurobiology of subterranean species. For example, we find that mole-rat brain physiology impacts survival after surgeries, with higher carbon dioxide concentrations required for recovery compared to other rodents, likely due to a mutation in the chloride-potassium symporter KCC2. Having addressed the challenges, we used tetrodes and Neuropixels probes to record single-unit activity and local field potentials (LFP) across several cortical and subcortical regions for several weeks. We observed single units responsive to auditory and visual stimuli in the superior colliculus, and hippocampal recordings in freely moving mole-rats revealed prominent theta rhythms at frequencies lower than those observed in any other rodent species to date. Finally, we performed integrated three-dimensional and two-dimensional probe-track analysis within the same brain using tissue clearing, light sheet imaging, rehydration, and vibratome sectioning, and we present a newly developed stereotaxic brain atlas for implantation and histological alignment. The established methodology will guide future studies in comparative rodent neurobiology, providing further insights into neurobiological adaptations to subterranean environments. Given their phylogenetic and ecological similarities, we expect our protocols to be transferable to other subterranean species, including the widely studied naked mole-rat (Heterocephalus glaber). HighlightsO_LIProtocols for chronic and acute electrode implantations in mole-rats C_LIO_LIStereotaxic brain atlas for the Ansells mole-rat (https://doi.org/10.17617/3.UNDKRO) C_LIO_LINeuropixels and tetrode single-unit recordings in head-fixed and freely moving mole-rats C_LIO_LIIntegrated 3D (tissue clearing) and 2D (histology) probe-track analysis within the same brain C_LIO_LIDiscovery of low-frequency hippocampal theta rhythm in Ansells mole-rats C_LI

neuroscience↗

Physiological Basis of noise-induced hearing loss in a tympanal ear

Acoustic overexposure, such as listening to music too loud and too often, results in noise-induced hearing loss. The pathologies of this prevalent sensory disorder begin in the synapses of the primary auditory receptors, their postsynaptic partners and supporting cells. The extent of noise-induced damage, however, is determined by over-stimulation of primary auditory receptors. When over-stimulated, an excessive amount of positive ions flood into the primary auditory receptors, triggering the activation of ion channels and possibly disrupting their ability to encode sound. A systematic characterisation of the electrophysiological function of primary auditory receptors is warranted to understand how noise-exposure impacts on downstream targets, where the pathologies of hearing loss begin. Here, we used the experimentally-accessible locust ear to characterise noise-induced changes in the auditory receptors. Although, we found a decrease in ability of the primary auditory neurons to encode sound, this is probably due to pathologies of their supporting cells.

neuroscience↗