Biology subjects

O'Neil, K.

Publications and source records attributed to O'Neil, K..

8 recordsLinked to original sources

bioRxiv2026

Temporal Coding rather than Circuit Wiring allows Hippocampal CA3 Neurons to Dynamically Distinguish Different Cortical Inputs

Memory relies on associating and indexing multimodal information. How does this occur within single neurons? The hippocampus integrates multisensory information from medial (MEC) and lateral (LEC) entorhinal cortices to form environmental representations1-6, yet their synaptic dynamics, circuit organization, and integrative functions remain elusive. Contrary to canonical models emphasizing anatomical and functional segregation, our dual-color optogenetic7 circuit mapping revealed that both MEC and LEC inputs converge on virtually every CA3 pyramidal neuron and exhibit similar input-output functions and modulation via GABAergic microcircuitry. Divergence occurs in their frequency-dependent short-term plasticity. With increasing frequencies, facilitating LEC-evoked responses undergo synaptic depression, whereas MEC-evoked responses continue facilitating. In vivo, MEC-originating dentate spikes fire CA3 more than LEC, likely due to their distinct temporal relationship with oscillatory activity. Our findings support that hippocampal area CA3 processes region-specific information from MEC and LEC via temporal coding, rather than hard-wired circuit organization, at both single-neuron and network levels.

neuroscience↗

bioRxiv2025

Complementary cortical and thalamic contributions to cell-type-specific striatal activity dynamics during movement

Coordinated motor behavior emerges from information flow across brain regions. How long-range inputs drive cell-type-specific activity within motor circuits remains unclear. The dorsolateral striatum (DLS) contains direct- and indirect-pathway medium spiny neurons (dMSNs and iMSNs) with distinct roles in movement control. In mice performing skilled locomotion, we recorded from dMSNs, iMSNs, and their cortical and thalamic inputs identified by monosynaptic rabies tracing. An RNN classifier and clustering analysis revealed functionally heterogeneous subpopulations in each population, with dMSNs preferentially activated at movement onset and offset, and iMSNs during execution. Cortical and thalamic inputs were preferentially activated during onset/offset and execution, respectively, though dMSN- and iMSN-projecting neurons in each region showed similar patterns. Locomotion phase-specific rhythmic activity was found in a subset of thalamic dMSN-projecting neurons and dMSNs. Cortex or thalamus inactivation reduced MSN activity. These findings suggest that corticostriatal and thalamostriatal inputs convey complementary motor signals via shared and cell-type-specific pathways.

neuroscience↗

bioRxiv2025

Status of Florida's pillar coral population: in situ declines and ex situ successes

The population of the pillar coral, Dendrogyra cylindrus, in Florida was decimated from 2013-2020, primarily by the emergence of stony coral tissue loss disease (SCTLD). Monitoring of survivors from 2021 - early 2025 showed that the population underwent an additional 96% decline in live tissue, 78% loss in living colonies, and 57% loss of genotypes. SCTLD continued to be the primary cause of these losses. Though some surviving tissue isolates exhibited small amounts of growth, the population remains extremely small, with only an estimated 9.6 square meters of tissue remaining on 23 colonies (15 genotypes). Additionally, colonies are far too dispersed to successfully fertilize spawned gametes. The further declines in the population since 2020 highlight the instability of the remnant population, as well as the value of the pillar coral rescue program and ongoing propagation efforts. As of February 2025, eight different in situ and ex situ facilities were caring for rescued D. cylindrus. Experimental fragmentation at one in situ nursery identified variable, but continually increasing, growth rates across multiple fragmentation events. Sexual propagation efforts at an ex situ nursery documented 105 different rescue fragments spawning across five years. The smallest fragment was 9 x 7 x 9 cm, establishing a potential "minimum colony size" for reproductive capacity for this species. From these spawning events, 82 juveniles were being raised ex situ in early 2025. Two of these sexually propagated juveniles spawned six years after settlement, thus establishing a potential minimum age for reproduction.

ecology↗

bioRxiv2025

Decreased female survival may explain wild turkey decline

Recent declines in wild turkey (Meleagris gallopavo) populations have prompted extensive research efforts and adjustments to state hunting regulations across the range of wild turkeys. However, research comparing historical and modern vital rates is needed to identify demographic factors that may explain declines. Based on matrix models, adult female survival has the greatest effect on the intrinsic rate of growth. Thus, we hypothesized that changes in annual female survival may explain contemporary declines in populations if that vital rate has decreased concomitant with population declines. We searched peer-reviewed literature, student theses and dissertations, and government reports for empirical estimates of annual female survival across the range of wild turkeys. Of the 51 resulting estimates of annual female survival across all subspecies, most were [≥]0.6 through 2012, but 8 out of 10 estimates post-2012 were lower, consistent with observed trends in population trajectories. We used matrix models to illustrate that the observed change in annual female survival estimates indeed predicts a declining population trajectory, even when other important vital rates are at the high end of the published range of process variation. If the published annual female survival estimates represent those experienced more broadly in populations, our meta-analysis and matrix models indicate that decreases in this vital rate help explain declines observed in populations in some regions. The causative factor(s) associated with the apparent declines are unknown, and little research has evaluated management strategies to increase annual female survival. Accordingly, we encourage wild turkey researchers to focus efforts on producing robust estimates of annual female survival, cause-specific mortality, and rigorous evaluation of management strategies to improve annual female survival.

zoology↗

bioRxiv2025

Assisted gene flow yields Acropora palmata corals with robust physiological performance under warmer water temperatures in a land-based nursery

Assisted gene flow (AGF) is a conservation approach that facilitates the spread of alleles and may accelerate the recovery of genetically depauperate cohorts. The threatened Caribbean coral Acropora palmata is approaching regional extinction within the western Atlantic partly due to increasing water temperatures associated with global climate change. Previously, AGF was conducted by crossing gametes collected from three regions (Curacao - CU, Florida - FL, and Puerto Rico - PR) characterized by contrasting temperature regimes and low gene flow between them. Here, we tested the thermal tolerance of these AGF cohorts in comparison to purebred Florida and Curacao cohorts. Exposure to high temperatures resulted in few physiological changes, likely because the corals hosted the thermally tolerant algal symbiont, Durusdinium trenchii. However, the FL x FL cohort was the most sensitive to the high temperatures with a significant reduction in net photosynthesis and maximum electron transport rate under this treatment. Like the phenotypic responses, gene expression changes in response to heat stress were muted overall. Consequently, there was little power to detect correlations between genotype and phenotype. Relative to mid-parent values, CUxFL AGF cohorts showed 26 overexpressed and 48 underexpressed genes. Differentially expressed genes included known stress responders. Importantly, hybrid crosses harbored 879 private alleles that were previously not recovered in representative genets from Florida and thus carry important conservation value. These findings suggest that AGF corals not only carry novel alleles but also represent novel gene expression patterns.

ecology↗

bioRxiv2024

Nanopore-based native RNA sequencing of human transcriptomes reveals the complexity of mRNA modifications and crosstalk between RNA regulatory features

The identification and functional characterization of chemical modifications on an mRNA molecule, in particular N6-methyladenosine (m6A) modification, significantly broadened our understanding of RNA function and regulation. While interactions between RNA modifications and other RNA features have been proposed, direct evidence showing correlation is limited. Here, using Oxford Nanopore long-read direct RNA sequencing (dRNA-seq), we simultaneously interrogate the transcriptome and epitranscriptome of a human leukemia cell line to investigate the correlation between m6A modifications, mRNA abundance, polyA tail length and alternative splicing. We demonstrated that high quality dRNA-seq is critically important for unbiased and large-scale correlative analyses of these RNA features. The genome wide landscape of RNA methylation was captured with single nucleotide and individual isoform resolution. The length of polyA tails were ascribed to individual transcripts and genes, allowing for unprecedent measurement of polyA tail length distribution. Global analysis indicated negative association between polyA tail length and mRNA abundance while uncovering pathway-specific responses upon depletion of m6A forming enzyme METTL3. Overall, our study presented a rich dRNA-seq data resource which has been validated and can be further exploited to inquire into the complexity of RNA modifications and potential interplays between RNA regulatory elements.

genomics↗

bioRxiv2023

Entorhinal cortex glutamatergic and GABAergic projections bidirectionally control discrimination and generalization of hippocampal representations

Discrimination and generalization are crucial brain-wide functions for memory and object recognition that utilize pattern separation and completion computations. Circuit mechanisms supporting these operations remain enigmatic. We show lateral entorhinal cortex glutamatergic (LECGLU) and GABAergic (LECGABA) projections are essential for object recognition memory. Silencing LECGLU during in vivo two-photon imaging increased the population of active CA3 pyramidal cells but decreased activity rates, suggesting a sparse coding function through local inhibition. Silencing LECGLU also decreased place cell remapping between different environments validating this circuit drives pattern separation and context discrimination. Optogenetic circuit mapping confirmed that LECGLU drives dominant feedforward inhibition to prevent CA3 somatic and dendritic spikes. However, conjunctively active LECGABA suppresses this local inhibition to disinhibit CA3 pyramidal neuron soma and selectively boost integrative output of LEC and CA3 recurrent network. LECGABA thus promotes pattern completion and context generalization. Indeed, without this disinhibitory input, CA3 place maps show decreased similarity between contexts. Our findings provide circuit mechanisms whereby long-range glutamatergic and GABAergic cortico-hippocampal inputs bidirectionally modulate pattern separation and completion, providing neuronal representations with a dynamic range for context discrimination and generalization.

neuroscience↗

bioRxiv2018

CONSTRUCTION OF WHOLE GENOMES FROM SCAFFOLDS USING SINGLE CELL STRAND-SEQ DATA

Accurate reference genome sequences provide the foundation for modern molecular biology and genomics as the interpretation of sequence data to study evolution, gene expression and epigenetics depends heavily on the quality of the genome assembly used for its alignment. Correctly organising sequenced fragments such as contigs and scaffolds in relation to each other is a critical and often challenging step in the construction of robust genome references. We previously identified misoriented regions in the mouse and human reference assemblies using Strand-seq, a single cell sequencing technique that preserves DNA directionality1, 2. Here we demonstrate the ability of Strand-seq to build and correct full-length chromosomes, by identifying which scaffolds belong to the same chromosome and determining their correct order and orientation, without the need for overlapping sequences. We demonstrate that Strand-seq exquisitely maps assembly fragments into large related groups and chromosome-sized clusters without using new assembly data. Using template strand inheritance as a bi-allelic marker, we employ genetic mapping principles to cluster scaffolds that are derived from the same chromosome and order them within the chromosome based solely on directionality of DNA strand inheritance. We prove the utility of our approach by generating improved genome assemblies for several model organisms including the ferret, pig, Xenopus, zebrafish, Tasmanian devil and the Guinea pig.

genomics↗