Biology subjects

Harvey, B. M.

Publications and source records attributed to Harvey, B. M..

8 recordsLinked to original sources

bioRxiv2024

Glial cell derived pathway directs regenerating optic nerve axons toward the CNS midline

After optic nerve injury, several retinal ganglion cell (RGC) intrinsic signaling pathways have been shown to enhance RGC survival and RGC axonal growth. In contrast, few extrinsic cues have been identified that guide regenerating RGC axons toward and across the optic chiasm. Here, we use live-cell imaging in larval zebrafish to show that regrowing RGC axons initiate growth toward the midline and extend along a trajectory similar to their original projection. From a candidate genetic screen, we identify the glycosyltransferase Lh3 (also referred to as Plod3) to be required to direct regrowing RGC axons toward the midline during active regeneration. Moreover, we show that transgenic lh3 expression in sox10+ presumptive olig2+ oligodendrocytes located near the optic chiasm restores directed axonal growth in lh3 mutants. Finally, we find that mutants in collagen 18a1 (col18a1), a putative Lh3 substrate, display RGC axonal misguidance phenotypes similar to lh3 mutants, suggesting that lh3 may act through col18a1 during regeneration. Combined, these data identify lh3 as part of a glial derived molecular pathway critical for guiding in vivo regenerating RGC axons toward and across the optic chiasm.

neuroscience↗

bioRxiv2024

Numerosity adaptation suppresses early visual responses

Humans and many animals rapidly and accurately perceive numerosity, the number of objects, in a visual image. The numerosity of recently viewed images influences our perception of the current images numerosity: numerosity adaptation. How does numerosity adaptation affect responses to numerosity in the brain? Recent studies show both early visual responses that monotonically increase with numerosity, and later numerosity-tuned responses that peak at different (preferred) numerosities in different neural populations. We have recently shown that numerosity adaptation affects the preferred numerosity of numerosity-tuned neural populations. We have also shown that early visual monotonic responses reflect image contrast, which follows numerosity closely. Here we ask how monotonic responses in the early visual cortex are affected by adaptation to different numerosities, using ultra-high field (7T) fMRI and neural model-based analyses. FMRI response amplitudes increased monotonically with numerosity throughout the early visual field maps (V1-V3, hV4, LO1-LO2 & V3A/B). This increase in response amplitudes becomes less steep after adaptation to higher numerosities, with this effect becoming stronger through the early visual hierarchy. This suppression of responses to numerosity is consistent with perceptual effects where adaptation to high numerosities reduces the perceived numerosity. These results imply that numerosity adaptation effects in later numerosity-tuned neural populations may originate in early visual areas that respond to image contrast in the adapting image.

neuroscience↗

bioRxiv2024

Transitions from monotonic to tuned responses in recurrent neural network models during timing prediction

The brain exhibits a gradual transition in responses to visual event duration and frequency through the visual processing hierarchy: from monotonically increasing to timing-tuned responses. Over their hierarchies, properties of both response types are progressively transformed. Here, we implement simulations based on artificial neural networks to investigate the requirements of neural systems for the emergence of such responses and their properties transformations. We see that recurrent networks develop monotonic responses whose properties progressions over network layers resemble those over brain areas. Responses to another sensory quantity, Furthermore, recurrent networks can further develop tuned responses, but only with training, a gradual transition between monotonic and tuned responses emerges. Particularly, if this training is done on predictable sequences, the tuned properties progressions resemble those observed in the brain. These results suggest that the emergence of visual timing-tuned responses and the subsequent hierarchical transformations of these responses result from recurrent neural computation and predictive processing of sensory event timing.

neuroscience↗

bioRxiv2024

Upregulated cholesterol biosynthesis facilitates the survival of methylation-retaining AML cells following decitabine treatment.

DNA hypomethylating agents (HMAs) are used to treat acute myeloid leukemia (AML) and myelodysplasia patients who are unsuitable for intensive chemotherapy. However, low response rates and therapy-resistant relapse remain significant challenges. To improve outcomes, we must understand how AML cells survive HMA treatment and continue to proliferate following therapy. We combine single-cell multiomics with parallel colony-forming assays to link HMA-induced heterogeneity with functional consequences in AML cellss. Azacytidine (AZA) and decitabine (DAC) induced global epigenetic heterogeneity, associated with upregulation of inflammatory responses and cell death pathways in a subset of hypomethylated cells. Some cells maintained high DNA methylation levels during treatment, and these methylation-retaining cells had increased self-renewal capacity following DAC treatment in two FLT3-ITD AML cell lines. Transcriptional profiling of colonies formed after HMA treatment revealed many genes with altered expression in both methylation-retaining and hypomethylated cells, with increased expression of cholesterol-related genes observed in all cell lines. Inhibition of the cholesterol biosynthesis pathway by rosuvastatin enhanced HMA effects on colony formation in vitro and extended survival in two in vivo models of AML. Our study demonstrates that HMA-induced epigenetic heterogeneity has implications for AML cell growth and identifies statins as a candidate co-treatment strategy to improve HMA efficacy.

cancer biology↗

bioRxiv2021

Transformation from local image contrast to location-independent numerosity tuning in human extrastriate cortex

Human early visual cortex response amplitudes monotonically increase with numerosity (object number), regardless of object size and spacing. However, numerosity is typically considered a high-level visual or cognitive feature, while early visual responses follow image contrast in the spatial frequency domain. We found that, at fixed contrast, aggregate Fourier power (at all orientations and spatial frequencies) followed numerosity closely but nonlinearly with little effect of object size, spacing or shape. This would allow straightforward numerosity estimation from spatial frequency domain image representations. Using 7T fMRI, we showed monotonic responses originate in primary visual cortex (V1) at the stimuluss retinotopic location. Responses here and in neural network models followed aggregate Fourier power more closely than numerosity. Truly numerosity tuned responses emerged after lateral occipital cortex and were independent of retinotopic location. We propose numerositys straightforward perception and neural responses may have built on behaviorally beneficial spatial frequency analyses in simpler animals.

neuroscience↗

bioRxiv2021

Encoding of motion by spatial and temporal frequency in the human middle temporal cortex measured by 7T fMRI

Perception of dynamic scenes in our environment results from the evaluation of visual features such as the fundamental spatial and temporal frequency components of a moving object. The ratio between these two components represents the objects speed of motion. The human middle temporal cortex hMT+ has a crucial biological role in the direct encoding of object speed. However, the link between hMT+ speed encoding and the spatiotemporal frequency components of a moving object is still under explored. Here, we recorded high resolution 7T blood oxygen level-dependent BOLD responses to different visual motion stimuli as a function of their fundamental spatial and temporal frequency components. We fitted each hMT+ BOLD response with a 2D Gaussian model allowing for two different speed encoding mechanisms: 1) distinct and independent selectivity for the spatial and temporal frequencies of the visual motion stimuli 2) pure tuning for the speed of motion. We show that both mechanisms occur but in different neuronal groups within hMT+, with the largest subregion of the complex showing separable tuning for the spatial and temporal frequency of the visual stimuli. Both mechanisms were highly reproducible within participants, reconciling single cell recordings from MT in animals that have showed both encoding mechanisms. Our findings confirm that a more complex process is involved in the perception of speed than initially thought and suggest that hMT+ plays a primary role in the evaluation of the spatial features of the moving visual input.

neuroscience↗

bioRxiv2020

Linked deterioration of early visual perception, function and structure in healthy human aging

Low-level visual perception deteriorates during healthy aging. We hypothesized that age-related retinal and cortical structure deteriorations affect perception through specific disruptions of neural function. We measured perceptual visual acuity in fifty healthy adults aged 20-80 years. We then measured these participants early visual field map (V1, V2 and V3) functional population receptive field (pRF) sizes and structural surface areas using fMRI, and their retinal structure using high-definition optical coherence tomography. With increasing age visual acuity decreased, pRF sizes increased, visual field maps surface areas decreased, and retinal thickness decreased. Among these measures, only functional pRF sizes predicted perceptual visual acuity. PRF sizes were in turn predicted by cortical structure only (surface areas), which were only predicted by retinal structure (thickness). We propose that age-related retinal structural deterioration disrupts cortical structure, thereby disrupting cortical functional neural interactions that normally sharpen visual position selectivity: the resulting functional disruption underlies age-related perceptual deterioration.

neuroscience↗

bioRxiv2017

Propagation of BOLD activity reveals directed interactions across human visual cortex

It has recently been shown that large-scale propagation of blood-oxygen level dependent (BOLD) activity is constrained by anatomical connections and reflects transitions between behavioral states. It remains to be seen, however, if the propagation of BOLD activity can also relate to the brain anatomical structure at a more local scale. Here, we hypothesized that BOLD propagation reflects structured neuronal activity across early visual field maps. To explore this hypothesis, we characterize the propagation of BOLD activity across V1, V2 and V3 using a modeling approach that aims to disentangle the contributions of local activity and directed interactions in shaping BOLD propagation. It does so by estimating the effective connectivity (EC) and the excitability of a noise-diffusion network to reproduce the spatiotemporal covariance structure of the data. We apply our approach to 7T fMRI recordings acquired during resting state (RS) and visual field mapping (VFM). Our results reveal different EC interactions and changes in cortical excitability in RS and VFM, and point to a reconfiguration of feedforward and feedback interactions across the visual system. We conclude that the propagation of BOLD activity has functional relevance, as it reveals directed interactions and changes in cortical excitability in a task-dependent manner.

neuroscience↗