Biology subjects

Fitzgerald, E.

Publications and source records attributed to Fitzgerald, E..

5 recordsLinked to original sources

bioRxiv2023

Biomimetic multi-channel microstimulation of somatosensory cortex conveys high resolution force feedback for bionic hands

AO_SCPLOWBSTRACTC_SCPLOWManual interactions with objects are supported by tactile signals from the hand. This tactile feedback can be restored in brain-controlled bionic hands via intracortical microstimulation (ICMS) of somatosensory cortex (S1). In ICMS-based tactile feedback, contact force can be signaled by modulating the stimulation intensity based on the output of force sensors on the bionic hand, which in turn modulates the perceived magnitude of the sensation. In the present study, we gauged the dynamic range and precision of ICMS-based force feedback in three human participants implanted with arrays of microelectrodes in S1. To this end, we measured the increases in sensation magnitude resulting from increases in ICMS amplitude and participants ability to distinguish between different intensity levels. We then assessed whether we could improve the fidelity of this feedback by implementing "biomimetic" ICMS-trains, designed to evoke patterns of neuronal activity that more closely mimic those in natural touch, and by delivering ICMS through multiple channels at once. We found that multi-channel biomimetic ICMS gives rise to stronger and more distinguishable sensations than does its single-channel counterpart. Finally, we implemented biomimetic multi-channel feedback in a bionic hand and had the participant perform a compliance discrimination task. We found that biomimetic multi-channel tactile feedback yielded improved discrimination over its single-channel linear counterpart. We conclude that multi-channel biomimetic ICMS conveys finely graded force feedback that more closely approximates the sensitivity conferred by natural touch.

neuroscience↗

bioRxiv2022

The coarse mental map of the breast is anchored on the nipple

AO_SCPLOWBSTRACTC_SCPLOWTouch plays a key role in our perception of our body and shapes our interactions with the world, from the objects we manipulate to the people we touch. While the tactile sensibility of the hand has been extensively characterized, much less is known about touch on other parts of the body. Despite the important role of the breast in lactation as well as in affective and sexual touch, relatively little is known about its sensory properties. To fill this gap, we investigated the ability of women to locate touches on the breast and compared it to that of the hand and back, body regions that span the range of tactile discriminative capabilities. First, we found that the tactile precision of the breast was even lower than that of the back, heretofore the paragon of poor precision. Second, precision was lower for breasts that had undergone greater expansion, consistent with the hypothesis that innervation capacity does not scale with body size. Third, touches to different regions of the nipple were largely indistinguishable, suggesting sparse innervation density. Fourth, localization errors were systematically biased toward the nipple. SO_SCPLOWIGNIFICANCEC_SCPLOWOur basic understanding of the tactile capabilities of the breast remains poorly understood in comparison to the hand or face despite the fact that the breast plays a major role in the lives of those with breasts. This paper establishes common methods for studying breast tactile sensation and presents the breast and nipple as two fundamentally discrete tactile units from the torso.

neuroscience↗

bioRxiv2020

A transient role of primary cilia in controlling direct versus indirect neurogenesis in the developing cerebral cortex

During the development of the cerebral cortex, neurons are generated directly from radial glial cells or indirectly via basal progenitors. The balance between these division modes determines the number and types of neurons formed in the cortex thereby affecting cortical functioning. Here, we investigate the role of primary cilia in this process. We show that a mutation in the ciliary gene Inpp5e leads to a transient increase in direct neurogenesis and subsequently to an overproduction of layer V neurons in newborn mice. Loss of Inpp5e also affects ciliary structure coinciding with increased Akt and mTOR signalling and reduced Gli3 repressor levels. Genetically re-storing Gli3 repressor rescues the decreased indirect neurogenesis in Inpp5e mutants. Overall, our analyses reveal how primary cilia determine neuronal subtype composition of the cortex by controlling direct vs indirect neurogenesis. These findings have implications for understanding cortical malformations in ciliopathies with INPP5E mutations.

developmental biology↗

bioRxiv2020

Altered hypothalamic DNA methylation and stress-induced hyperactivity in a novel model of early life stress

Early life stress during childhood is associated with a number of psychiatric disorders that manifest across the life course. Preterm birth is a profound stressor, and an important cause of cognitive impairment, as well as neurodevelopmental and psychiatric disorders. However, the mechanisms that link events during the early neonatal period with later functional problems are poorly understood. We developed a novel mouse model of early life stress (modified maternal separation; MMS) with specific relevance to preterm birth (PTB) and hypothesised it would affect the hypothalamic transcriptome and DNA methylome and impact on behaviour in adulthood. MMS consisted of repeatedly stimulating pups for 1.5 hours/day, whilst separated from their mother, from postnatal day (P)4-6. 3 RNA sequencing and DNA methylation immunoprecipitation (meDIP) sequencing was performed on the hypothalamus at P6. Behaviour was assessed with the elevated plus and open field mazes, and in-cage monitoring at 3-4 months of age. Although MMS was only associated with subtle changes in gene expression there were widespread alterations in DNA methylation. Notably, differentially methylated regions were enriched for synapse-associated loci. MMS also resulted in hyperactivity in the elevated plus and open field mazes, but in-cage monitoring revealed that this was not representative of habitual hyperactivity. In conclusion we describe a novel model of early life stress with relevance to PTB, with marked effects on DNA methylation in the hypothalamus and with stress-specific hyperactivity in young adulthood. We suggest that these results have implications for the understanding of early life stress mediated effects on brain development.

developmental biology↗

bioRxiv2018

Propionic acid enhances the virulence of Crohn’s disease-associated adherent-invasive Escherichia coli

The short chain fatty acid propionic acid (PA) is a bacteria-derived human intestinal antimicrobial and immune modulator used widely in Western food production and agriculture. Here we examine the effect of PA on the pathogenicity of the Crohns disease-associated microbe, adherent-invasive Escherichia coli (AIEC). Passage of AIEC through a murine model, where the low intestinal PA levels were increased to replicate those of the human intestine, led to the recovery of AIEC post-infection that had significantly increased virulence. These phenotypic changes, including increased adhesion to intestinal epithelial cells and biofilm formation, could be replicated in AIEC in vitro through exposure to PA alone. This in vitro exposure of AIEC to PA fundamentally changed AIEC virulence, with strains exposed to PA in vitro subsequently persisting at 20-fold higher levels in a murine model compared to non-exposed strains. RNA-sequencing identified the transcriptional changes in AIEC in response to PA with upregulation of genes involved in biofilm formation, stress responses, metabolism, membrane integrity and alternative carbon source utilisation. These PA induced changes in virulence could be replicated in a number of E. coli isolates from Crohns disease patients. Finally, removal of the PA selective pressure was sufficient to reverse these phenotypic changes. Our data indicate that exposure of AIEC to PA evolves bacteria that are both resistant to this natural human intestinal antimicrobial and increasingly virulent in its presence.\n\nImportanceExposure to propionic acid, an intestinal short chain fatty acid and commonly used antimicrobial in Western food production, induces significant virulence associated phenotypic changes in adherent-invasive Escherichia coli (AIEC).

microbiology↗