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Aubier, T.

Publications and source records attributed to Aubier, T..

4 recordsLinked to original sources

Focal Neurostimulation of Calcium Signaling and Dopamine Release in Human Dopaminergic Neurons Using Megahertz-range Single-Pulse Focused Ultrasound

Focused Ultrasound (FUS) neurostimulation has increasingly attracted attention given its ability for localized targeting and non- to minimally-invasive capacity. However, the understanding of the biological and neurochemical mechanisms triggered by this neurostimulation modality remains limited. Indeed, further progress of this technology could benefit from spatiotemporal evaluation of neurotransmitter secretory activity resulting from FUS stimulation. Recently, we demonstrated in-vitro the ability of FUS to evoke calcium (Ca2+) waves, in a mixture of human neuronal and glial cells (standard cells), with single-pulse megahertz-range FUS compatible with a transdural approach relying on an intracranial FUS implant. In the present work, we investigated the ability to evoke Ca2+ signaling and dopamine (DA) release by single-pulse megahertz-range FUS stimulation of cultured human dopaminergic neurons in-vitro. A hybrid-platform integrating a custom-made FUS implant prototype (concave spherical transducer, O and focal distance: 15 mm) with real-time Ca2+ fluorescence microscopy imaging (FMI), and fast scan cyclic voltammetry (FSCV) was constructed to evaluate FUS-evoked Ca2+ signaling and concurrent DA release. Ca2+ and DA releases evoked by FUS on dopaminergic neurons (DA neurons) were compared to those evoked in standard cells. Application of single-pulse FUS (frequency: 5.11 MHz, pulse duration: 700 {micro}s, spatial average pulse average intensity, Isapa: 19.59 {+/-} 4.12 W.cm-2) was shown to causally mobilize Ca2+ dynamics in both cell types. Immediate (< 1 s) responses were focally evoked in cell clusters of 290 {micro}m in diameters; corresponding to the -3 dB FUS focal diameter. However, while standard cells exhibited continuous and omnidirectional delayed propagating dynamics following FUS stimulation, DA neurons showed more spatially sparse responses. The FUS-induced Ca2+ activity in DA neurons was accompanied by DA release detected by FSCV, but not in standard cells. This study demonstrates that single-pulse megahertz-range FUS induced with an intracranial implant prototype smaller than conventionally used FUS devices (transcranial applications) can evoke in-vitro intracellular Ca2+ activity while stimulating DA release from dopaminergic neurons, underscoring its potential as a neuro-stimulation/-modulation tool for targeting dopaminergic circuits in various pathologies.

bioengineering↗

Focal neurostimulation of propagating calcium waves in human neural cells using megahertz-range single-pulse focused ultrasound

Focused ultrasound (FUS) offers a promising neurostimulation technique that addresses the trade-off between invasiveness and spatial selectivity found in conventional electromagnetic-based methods. Evidence supporting its theoretical selectivity and comprehensive descriptions of the underlying biophysical mechanisms remain insufficient to ensure adequate control and safety. Based on observations of causal, focal, and propagating calcium waves in human neural cells in vitro evoked using single-pulse megahertz-range FUS, a transdural FUS approach relying on an intracranial implant is proposed to overcome frequency limitations associated with transcranial ultrasound. Using an extended parameter space (0.7 -8 MHz), calcium waves were shown to be selectively elicited by cavitation or acoustic radiation force. Cavitation, predominant at frequencies under 5 MHz, induced dispersed and unpredictable responses that could lead to cell damage. FUS radiation force however, predominant at frequencies over 5 MHz, elicited focal and predictable responses, without affecting cell viability. FUS-evoked intercellular calcium waves were shown to propagate across the surrounding neural network via intracellular and extracellular pathways driven by calcium amplification mechanisms. Collectively, these findings lay the foundation for developing wearable neurostimulation approaches to manage chronic neurological conditions.

bioengineering↗

The 'sexual selection hypothesis' for the origin of aposematism

The evolution of aposematism, in which prey exhibit conspicuous signals indicating the presence of anti-predator defenses, is puzzling. Before predators learn to associate the signal with defense, increased visibility makes the conspicuous prey highly vulnerable to predation. Although several hypotheses have been proposed to explain the evolution of aposematism, they often assume that these signals can only be recognized by predators. Yet, many studies show that aposematic signals can also be involved in mate choice. Here, we demonstrate that some aposematic signals may have originally evolved as mating signals driven by sexual selection. In this study, we analyze a mathematical model to explore how sexual selection can drive the evolution of aposematism. We thereby identify key features of this sexual selection hypothesis for the origin of aposematism to be tested with empirical data. Our results show that the evolution of conspicuous signals through sexual selection increases the visibility of prey to predators and thus predation pressure. This, in turn, promotes the evolution of defense mechanisms, ultimately leading to aposematism when predators learn to associate the signal with defense. Additionally, we show that when sexual selection drives the evolution of aposematism, it often results in sexual dimorphism in both signaling and defense traits.

evolutionary biology↗

Admixture can readily lead to the formation of supergenes

Supergenes are genetic architectures allowing the segregation of alternative combinations of alleles underlying complex phenotypes. The co-segregation of sets of alleles at linked loci is determined by polymorphic chromosomal rearrangements suppressing recombination locally. Supergenes are involved in many complex polymorphisms, including sexual, color or behavioral polymorphisms in numerous plants, fungi, mammals, fish, and insects. Despite a long history of empirical and theoretical research, the genetic origin of supergenes remains poorly understood. Here, using a population genetic two-island model, we explore how the evolution of overdominant chromosomal inversions may lead to the formation of supergenes. We show that the evolution of inversions in differentiated populations connected by gene flow leads to an increase in frequency of poorly adapted, immigrant haplotypes. When inversions are associated with recessive fitness cost hampering their fixation (such as a mutational load), this results in the formation of supergenes. These results provide a realistic scenario for the evolution of supergenes and inversion polymorphisms in general, and bring new light into the importance of admixture in the formation of new genetic architectures.

evolutionary biology↗