Biology subjects

Arndt, S.

Publications and source records attributed to Arndt, S..

5 recordsLinked to original sources

bioRxiv2025

Interactions of Interaural Time and Level Differences in Spatial Hearing with Cochlear Implants

Normally hearing humans can localize sound sources quite accurately, with minimum audible angles as small as 1{degrees}. To achieve this, our auditory pathways combine information from multiple acoustic cues, including interaural time and interaural level differences (ITDs and ILDs). Patients relying on cochlear implants (CIs) to hear the world cannot match normal performance. These deficits are most pronounced in patients with little or no hearing experience early in life, and they appear to result from an impaired sensitivity to ITDs, but not to ILDs. However, little is known about how ITD and ILD sensitivities develop and interact in an early deafened auditory system shortly after CI implantation. We fitted neonatally deafened rats with bilateral CIs, and, providing informative ITDs and ILDs from stimulation onset, trained them to lateralize CI stimuli. These animals were exquisitely sensitive to both ILDs and ITDs of CI stimulus pulses, and combined information from both cues in a weighted sum. Importantly, ITDs are weighted heavily in our CI rats, such that only very modest ITDs pointing in one direction can confound quite large ILDs pointing in the opposite direction. This underlines the importance of informative ITDs for maximizing the potential for spatial hearing with CI devices. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/635454v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@15ee6e2org.highwire.dtl.DTLVardef@1881bd4org.highwire.dtl.DTLVardef@db17c7org.highwire.dtl.DTLVardef@1f62f2f_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Interaural level difference sensitivity in neonatally deafened rats fitted with bilateral cochlear implants

Bilateral cochlear implant (CI) patients exhibit significant limitations in spatial hearing. Their ability to process interaural time differences (ITDs) is often impaired, while their ability to process interaural level differences (ILDs) remains comparatively good. Clinical studies aiming to identify the causes of these limitations are often plagued by confounds and ethical limitations. Recent behavioral work suggests that rats may be a good animal model for studying binaural hearing under neuroprosthetic stimulation, as rats develop excellent ITD sensitivity when provided with suitable CI stimulation. However, their ability to use ILDs has not yet been characterized. Objective of this study is to address this knowledge gap. Neontally deafened rats were bilaterally fitted with CIs, and trained to lateralize binaural stimuli according to ILD. Their behavioral ILD thresholds were measured at pulse rates from 50 to 2400 pps. CI rats exhibited high sensitivity to ILDs with thresholds of a few dB at all tested pulse rates. We conclude that early deafened rats develop good sensitivity, not only to ITDs but also to ILDs, if provided with appropriate CI stimulation. Their generally good performance, in line with expectations from other mammalian species, validates rats as an excellent model for research on binaural auditory prostheses.

neuroscience↗

bioRxiv2024

Manipulation of the Nuclear Envelope-Associated Protein SLAPDuring Mammalian Brain Development Affects Cortical Lamination and Exploratory Behavior

Here we report the first characterization of the effects resulting from the manipulation of Soluble-Lamin Associated Protein (SLAP) expression during mammalian brain development. We found that SLAP localizes to the nuclear envelope and when overexpressed causes changes in nuclear morphology and lengthening of mitosis. SLAP overexpression in apical progenitors of the developing mouse brain altered asymmetric cell division, neurogenic commitment and neuronal migration ultimately resulting in unbalance in the proportion of upper, relative to deeper, neuronal layers. Several of these effects were also recapitulated upon Cas9-mediated knock-down. Ultimately, SLAP overexpression during development resulted in a reduction in subcortical projections of young mice and, notably, reduced their exploratory behavior. Our study shows the potential relevance of the previously uncharacterized nuclear envelope protein SLAP in neurodevelopmental disorders.

developmental biology↗

bioRxiv2021

GDAP1 loss of function inhibits the mitochondrial pyruvate dehydrogenase complex by altering the actin cytoskeleton

Charcot-Marie-Tooth (CMT) disease 4A is an autosomal-recessive polyneuropathy caused by mutations of ganglioside-induced differentiation-associated protein 1 (GDAP1), a putative glutathione transferase, which affects mitochondrial shape and alters cellular Ca2+ homeostasis. Here, we identify the underlying mechanism. We found that patient-derived motoneurons and GDAP1 knockdown SH-SY5Y cells display two phenotypes: more tubular mitochondria and a metabolism characterized by glutamine dependence and fewer cytosolic lipid droplets. GDAP1 interacts with the actin-depolymerizing protein Cofilin-1 in a redoxdependent manner, suggesting a role for actin signaling. Consistently, GDAP1 loss causes less F-actin close to mitochondria, which restricts mitochondrial localization of the fission factor dynamin-related protein 1, instigating tubularity. Changes in the actin cytoskeleton also disrupt mitochondria-ER contact sites. This results in lower mitochondrial Ca2+ levels and inhibition of the pyruvate dehydrogenase complex, explaining the metabolic changes upon GDAP1 loss of function. Together, these findings reconcile GDAP1-associated phenotypes and implicate disrupted actin signaling in CMT4A pathophysiology.

neuroscience↗

bioRxiv2020

Convergent evolution of conserved mitochondrial pathways underlies repeated adaptation to extreme environments

Extreme environments test the limits of life; yet, some organisms thrive in harsh conditions. Extremophile lineages inspire questions about how organisms can tolerate physiochemical stressors and whether the repeated colonization of extreme environments is facilitated by predictable and repeatable evolutionary innovations. We identified the mechanistic basis underlying convergent evolution of tolerance to hydrogen sulfide (H2S)--a toxicant that impairs mitochondrial function--across evolutionarily independent lineages of a fish (Poecilia mexicana, Poeciliidae) from H2S-rich springs. Using comparative biochemical and physiological analyses, we found that mitochondrial function is maintained in the presence of H2S in sulfide spring P. mexicana, but not ancestral lineages from nonsulfidic habitats, due to convergent adaptations in the primary toxicity target and a major detoxification enzyme. Genome-wide local ancestry analyses indicated that convergent evolution of increased H2S tolerance in different populations is likely caused by a combination of selection on standing genetic variation and de novo mutations. At a macroevolutionary scale, H2S tolerance in 10 independent lineages of sulfide spring fishes across multiple genera of Poeciliidae is correlated with the convergent modification and expression changes of genes associated with H2S toxicity and detoxification. Our results demonstrate that the modification of highly conserved physiological pathways associated with essential mitochondrial processes mediates tolerance to physiochemical stress. In addition, the same pathways, genes, and--in some instances--codons are implicated in H2S adaptation in lineages that span 40 million years of evolution. Significance StatementSome organisms can tolerate environments lethal for most others, but we often do not know what adaptations allow them to persist and whether the same mechanisms underly adaptation in different lineages exposed to the same stressors. Investigating fish inhabiting springs rich in toxic hydrogen sulfide (H2S), we show that tolerance is mediated by the modification of pathways that are inhibited by H2S and those that can detoxify it. Sulfide spring fishes across multiple genera have evolved similar modifications of toxicity targets and detoxification pathways, despite abundant lineage-specific variation. Our study highlights how constraints associated with the physiological consequences of a stressor limit the number of adaptive solutions and lead to repeatable evolutionary outcomes across organizational and evolutionary scales.

evolutionary biology↗