Biology subjects

Thompson, J. L.

Publications and source records attributed to Thompson, J. L..

4 recordsLinked to original sources

bioRxiv2026

Is that clear? Robust electrophysiological measures of the effects of prior knowledge on degraded speech perception.

Perception and sensation are not synonymous. Rather, perception is a process whereby sensory input is organized and interpreted in a behaviorally relevant way based on memory, experience, and context. One specific framework that is commonly invoked to explain perception is that of Bayesian inference. This framework casts perception as a probabilistic process whereby imprecise sensory data are combined with prior knowledge (prior) to determine what is consciously perceived (the posterior probability), which reflects the brains best guess as to the cause(s) of the sensory data. A striking behavioral example of how prior information can influence perception is seen in studies in which degraded speech is rendered intelligible by presenting information about the speech content in advance. Neurophysiological studies of this phenomenon have primarily focused on how it affects neural indices of low-level sensory encoding. The size of any reported effects on these indices tends to be much smaller - and much less consistent - than the notably large effects on perception that come with prior information. In the present study, we recorded EEG from 27 healthy adult participants (16 female) as they listened to degraded speech clips that were preceded by matching or mismatching text. Prior knowledge in the form of matching text led to a large perceptual pop-out effect when listening to degraded speech. Analyses of the resulting EEG revealed: 1) significant but relatively weak effects of prior information on EEG measures of the linguistic encoding of speech; and 2) a very large effect of prior information on an EEG signal that resembles a well-established neural index of perceptual evidence accumulation and that was strongly related to speech intelligibility ratings across participants. These EEG signals likely relate to separate components of a Bayesian inferential process during the predictive perception of degraded speech. As such, they have implications for understanding predictive perception more broadly and for future research on perceptual disturbances in clinical populations.

neuroscience↗

bioRxiv2026

The development of ToF-SIMS for in-situ glycosaminoglycan analysis

Glycosaminoglycans (GAGs) are linear polysaccharides with essential roles in a myriad of biological processes. Despite their biological importance, methods to determine both spatial and compositional information is limited. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) provides spatially resolved compositional information of biological molecules without enzymatic digestion or label incorporation, enabling unbiased analysis independent of enzyme or label selectivity, overcoming many current limitations in GAG analysis. Here, we present the identification and validation of GAG discriminatory ions from biological samples by comparison of spectra from purified GAGs and cells with genetically modified GAG biosynthetic pathways. Ions discriminatory of specific GAG sub-families are identified and related to GAG structural components. The analysis is applied to human induced pluripotent stem cells engineered to lack heparan sulphate (HS), where compensatory changes in GAG display that link to function were observed. Furthermore, the broad applicability and spatial resolution of the technique is highlighted through detection of a disease-induced reduction in HS within the individual glomeruli of diabetic mice.

biochemistry↗

bioRxiv2024

Microglia respond to elevated intraocular pressure and synapse loss in the visual thalamus in a mouse model of glaucoma.

Microglia are resident immune cells of the central nervous system and mediate a broad array of adaptations and responses during disease, injury, and development. Typically, microglia morphology is understood to provide a window into their functional state. However, it is apparent that they have the capacity to adopt a broad spectrum of functional phenotypes characterized by numerous morphological profiles and associated gene expression profiles. Glaucoma, which leads to blindness from retinal ganglion cell (RGC) degeneration, is commonly associated with elevated intraocular pressure and has been shown to trigger microglia responses within the retinal layers, at the optic nerve head, and in retinal projection targets in the brain. The goal of this study was to determine the relationship of microglia morphology to intraocular pressure and the loss of retinal ganglion cell output synapses in the dorsolateral geniculate nucleus (dLGN), a RGC projection target in the thalamus that conveys information to the primary visual cortex. We accomplished this by analyzing dLGN microglia morphologies in histological sections from DBA/2J mice, which develop a form of inherited glaucoma. Microglia morphology was analyzed using skeletonized Iba1-fluorescence images and fractal analyses of individually reconstructed microglia cells. We found that microglia adopted more simplified morphologies, characterized by fewer endpoints and less total process length per microglia cell. There was an age-dependent shift in microglia morphology in tissue from control mice (DBA/2JGpnmb+) that was accelerated in DBA/2J mice. Microglia morphological measurements correlated with cumulative intraocular pressure, immunofluorescence labeling for the complement protein C1q, and density of vGlut2-labeled RGC axon terminals. Additionally, fractal analysis revealed a clear distinction between control and glaucoma dLGN, with microglia from ocular hypertensive DBA/2J dLGN tissue showing an elongated rod-like morphology. RNA-sequencing of dLGN tissue samples showed an upregulation of immune system-related gene expression and several specific genes associated with microglia activation and potential neuroprotective functions. These results suggest that microglia in the dLGN alter their physiology to respond to RGC degeneration in glaucoma, potentially contributing to CNS adaptations to neurodegenerative vision loss.

neuroscience↗

bioRxiv2022

Reconstituting human somitogenesis in vitro

The segmented body plan of vertebrates is established during somitogenesis, a well-studied process in model organisms, but remains largely elusive in humans due to ethical and technical limitations. Despite recent advances with pluripotent stem cell (PSC)-based approaches1-5, a system that robustly recapitulates human somitogenesis in both space and time remains missing. Here, we introduce a PSC-derived mesoderm-based 3D model of human segmentation and somitogenesis, which we termed Axioloids, that captures accurately the oscillatory dynamics of the segmentation clock as well as the morphological and molecular characteristics of segmentation and sequential somite formation in vitro. Axioloids show proper rostrocaudal patterning of forming segments and robust anterior-posterior FGF/WNT signaling gradients and Retinoic Acid (RA) signaling components. We identify an unexpected critical role of RA signaling in the stabilization of forming segments, indicating distinct, but also synergistic effects of RA and extracellular matrix (ECM) on the formation and epithelialization of somites. Importantly, comparative analysis demonstrates striking similarities of Axioloids to the human embryo, further validated by the presence of the HOX code in Axioloids. Lastly, we demonstrate the utility of our Axioloid system to study the pathogenesis of human congenital spine diseases, by using patient-like iPSC cells with mutations in HES7 and MESP2, which revealed disease-associated phenotypes including loss of epithelial somite formation and abnormal rostrocaudal patterning. These results suggest that Axioloids represent a promising novel platform to study axial development and disease in humans.

developmental biology↗