Biology subjects

Green, R. J.

Publications and source records attributed to Green, R. J..

4 recordsLinked to original sources

bioRxiv2026

Optimization of High Molecular Weight DNA Extractions from Dried, Museum-Grade Insects Enables Long-Read Sequencing, Phylogenetics, and Methylation Profiling

Developing an effective DNA extraction method that meets requirements for long-read sequencing of poorly preserved samples, such as museum specimens or ancient material, offers new opportunities for genomic analysis of endangered or extinct species for which samples are rare. However, these samples often yield degraded and highly fragmented DNA, rendering long-read sequencing infeasible for many specimens residing in museum collections. Herein, we demonstrate a protocol for successfully extracting DNA of sufficient quality for sequencing on the Oxford Nanopore Technologies long-read sequencing PromethION platform from a desiccated, museum-grade blue carpenter bee specimen (Xylocopa caerulea). We find the protocol is reproducible across specimens and yields high levels of long, endogenous X. caerulea-derived DNA, highlighting the utility of our method for enabling genomic studies of historical collections. From a single flow cell, we assembled the full-length mitochondrial genome and used this assembly to perform a phylogenetic analysis, accurately placing our X. caerulea specimen among related Xylocopa species, thus demonstrating the phylogenetic utility of long-read museomics. Using these long-read data, we analyzed native CpG methylation, finding endogenous methylation signals that correlate with genic and exonic sequences. This method expands the feasibility of genomic and epigenomic analyses from challenging samples, enhancing our ability to investigate the genomes of endangered and extinct species through archival resources.

genomics↗

bioRxiv2026

Amyloid plaques drive long-range circuit reorganization in a mouse model of Alzheimer's disease

Amyloid plaques are a pathological hallmark of Alzheimers disease, but how they drive widespread neuronal dysfunction remains unclear. While studies in anesthetized animals show that plaques drive local hyperactivity1,2, it is unknown how this pathology shapes functional hippocampal maps in freely behaving animals. We combined chronic 1-photon calcium imaging, local field potential recordings, and post hoc 2-photon plaque imaging in freely behaving APP/PS1 mice across behavior and sleep to correlate real-time hippocampal activity and place coding with precise plaque topography. Here we show that plaques exert nonlocal, long-range effects on hippocampal activity that depend on plaque size, laminar position, and the animals behavioral state. Place cells, which encode spatial position and are normally uniformly distributed, are preferentially enriched near plaques, revealing an aberrant reorganization of plaque-adjacent neurons into the hippocampal map of space. In longitudinal experiments, pre-existing place cell locations do not predict future plaque sites, whereas hyperactivity during slow-wave sleep weakly predicts future amyloid deposition. These findings identify a mechanism by which amyloid pathology reorganizes brain circuits, degrading the functional architecture of the hippocampus and contributing to widespread dysfunction and cognitive impairment in Alzheimers disease.

neuroscience↗

bioRxiv2024

Impaired Hippocampal Reactivation Preceding Robust Aβ Deposition in a Model of Alzheimer's Disease

Current therapeutic strategies for Alzheimers disease (AD) target amyloid-beta (A{beta}) fibrils and high molecular weight protofibrils associated with plaques, but molecular cascades associated with AD may drive neural systems failure before A{beta} plaque deposition in AD. Employing hippocampal electrophysiological recordings and dynamic calcium imaging across the sleep-wake cycle in a freely behaving mouse model of AD before A{beta} plaques accumulated, we detected marked impairments of hippocampal systems function: In a spatial behavioral task, phase-amplitude coupling (PAC) of the hippocampal theta and gamma oscillations was impaired and place cell calcium fluctuations were hyper-synchronized with the theta oscillation. These changes were not observed in REM sleep. In subsequent slow wave sleep (SWS), place cell reactivation was reduced. These degraded neural functions underlying memory encoding and consolidation support targeting pathological processes of the pre-plaque phase of AD to treat and prevent hippocampal impairments.

neuroscience↗

bioRxiv2022

Target-distractor competition modulates saccade trajectories in space and object-space

Saccade planning and execution can be affected by a multitude of factors present in a target selection task. Recent studies have shown that the similarity between a target and nearby distractors affects the curvature of saccade trajectories, due to target-distractor competition. To further understand the nature of this competition, we varied the distance between and the similarity of complex target and distractor objects in a delayed match-to-sample task to examine their effects on saccade trajectories and better understand the underlying neural circuitry. For trials with short saccadic reaction times (SRTs) when target-distractor competition is still active, we found a robust effect of distance consistent with saccade vector averaging, whereas the effect of similarity suggested the existence of an object-based suppressive surround. At longer SRTs there was sufficient time for competition between the objects to complete and the distractor to be inhibited, which resulted in saccade trajectory deviations exhibiting the effects of a spatial suppressive surround. In terms of similarity, as the target-distractor similarity decreased, the initial saccade angle shifted towards the target, reflecting stronger distractor inhibition. There were no interactions between distance and similarity at any point in the time-course of target-distractor competition. Taken together, saccade trajectories reflect target-distractor competition that is affected independently by both spatial and object-space suppressive surrounds. The differences in saccade trajectories at short and long SRTs distinguish between active and completed decision-making processes. Thus, saccade responses are more beneficial than manual responses in studies of decision-making models. Significance StatementThis is the first study to determine that the distance and similarity between visual objects independently affect saccade trajectories driven by the target-distractor competition process. Thus, spatiotemporal and object identity factors separately feed into saccade planning and execution, resulting in modulations of saccade trajectory metrics which are based on spatial and object-space suppressive surround mechanisms. Furthermore, this modulation of trajectory metrics distinguishes between active and complete decision-making processes. The findings are important for understanding the dynamic networks guiding target selection and are relevant for further development of decision-making models, as well as eye-tracking applications in health and disease.

neuroscience↗