Biology subjects

O'Keefe, J.

Publications and source records attributed to O'Keefe, J..

13 recordsLinked to original sources

bioRxiv2026

PFOS and GenX Induce Mitochondrial Toxicity and Differentially Alter Respiratory Complex Activities in Liver and Brain

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants associated with adverse health effects, yet the mitochondrial consequences of exposure to individual PFAS and their mixtures remain incompletely understood. This study investigated the individual and combined effects of perfluorooctanesulfonic acid (PFOS) and hexafluoropropylene oxide dimer acid (GenX) on mitochondrial respiratory complex activities under acute, sub-chronic, and chronic exposure conditions. Acute effects were evaluated using isolated mouse liver and brain mitochondria, while repeated exposure was assessed in mice treated with PFOS, GenX, or their combination at 0.2, 2, and 10 mg/kg body weight for 1 month or 0.2 mg/kg for 5 months. PFAS distribution in plasma and brain tissues, mitochondrial oxidative phosphorylation (OXPHOS) protein expression, and predicted interactions with mitochondrial Complexes III and IV were also examined. Acute exposure inhibited Complex III and IV activities, with combined treatment generally producing greater inhibition than either compound alone. Following sub-chronic exposure, mitochondrial responses varied according to dose, treatment, and tissue, with more pronounced reductions in liver complex activities and comparatively limited changes in brain enzyme activities. Chronic low-dose exposure altered selected brain mitochondrial complex activities, while PFAS measurements revealed differences in plasma concentration and distribution across brain regions. OXPHOS protein expression also varied across brain regions and exposure conditions. Molecular docking indicated distinct predicted interaction patterns, with PFOS generally exhibiting more favorable scores at Complex III binding sites and GenX at selected Complex IV regions. Overall, these findings demonstrate exposure-dependent and tissue-specific mitochondrial responses to PFOS and GenX and highlight the importance of evaluating combined PFAS exposure across multiple exposure durations.

pharmacology and toxicology↗

bioRxiv2025

Asymmetric Spring and Autumn Phenology Control Growing Season Length in Temperate Deciduous Forests

Forest phenological responses to climatic variation among species and populations across broad spatial scales remain poorly understood. Here, we quantify four decades of phenological dynamics for 10 major deciduous tree species by compiling a unique dataset that integrates high spatial resolution remote sensing with extensive field inventory data across the Northeastern and Midwestern United States. We found that spring and autumn phenology impose asymmetric controls on growing season length, with spring regulating interannual variation and autumn driving long-term trends. Spring phenology across all species was primarily controlled by temperature, while autumn phenology was influenced by spring phenology and an interacting suite of species-specific environmental factors. Our study demonstrates the promise of combining high resolution remote sensing with forest inventory data to investigate phenological dynamics over large regions. More importantly, our results provide new insights into how species-specific sensitivities to environmental drivers regulate growing season length in temperate forests.

ecology↗

bioRxiv2025

Dissecting novel object exploration: a fully automated homecage-based novel object recognition test

The novel object recognition test is a frequently used memory test in rodents. Due to its ethological nature, cross-species relevance, and specificity to testing hippocampal and parahippocampal function, it has been widely applied in basic and translational research. However, its implementation proves challenging due to multiple uncontrolled factors. Here, we describe a fully automated homecage-based novel object recognition test for assessing long-term object memory in mice. We present an empirically guided computational model to show the robustness of this approach despite ambiguity in defining exploratory behaviours. We show that mice preferentially explored novel compared to familiar objects after 24-hour and 7-day retention periods, starting to discern them while still a distance away. The findings were replicated across two facilities. Furthermore, the ability to recognise the novel object depends on the mouses prior interactions with the replaced object after 24 hours, but not after 7 days. Finally, we showed that external factors may introduce undesired exploration biases, which can be addressed using relative instead of absolute discrimination measures. The fully automated homecage-based object recognition test will improve standardisation, rigour, and reproducibility, as well as expand our understanding of the factors influencing object exploratory behaviours and object memory. MotivationRecognition of objects as novel or familiar is an important cognitive memory function with cross-species relevance. Extensive work has provided a good understanding of the brain regions involved. Despite the apparent simplicity of novel object recognition (NOR) tests, they remain challenging due to their sensitivity to various uncontrolled experimental factors and differences in study design. Here, we report a fully automated standardised NOR test carried out in a mouses homecage, which minimises previously reported variability in NOR tests. HighlightsO_LIFully automated novel object recognition test for assessing long-term object memory in the mouses homecage C_LIO_LIA robust analysis pipeline described C_LIO_LITest replicated in two facilities with comparable results C_LIO_LIAn empirically guided computational model pointing to the robustness of this approach introduced C_LIO_LIMajor factors affecting the ability to discriminate novel from familiar objects, including object exploration bias, are described C_LI

neuroscience↗

bioRxiv2025

Hippocampal theta sweeps indicate goal direction

Successful spatial navigation requires rapid evaluation of potential future trajectories. Hippocampal "theta sweeps", sequential activation of place cells within individual theta cycles, exhibit predictive dynamics within the ideal timeframe to fulfill this role. However, whether these sequences simply reflect movement-related variables or afford more cognitive goal-directed planning remains unresolved. Using data from a navigation task on the "Honeycomb" maze that allows dissociation of head-, movement- and goal-direction correlates, we found that hippocampal theta sweeps exhibit robust goal-oriented directional biases, independent of movement- or head-direction. An existing model of theta sweeps, with an additional goal-oriented directional input, reproduces these findings and predicts goal-oriented theta phase precession, which we confirm empirically. Replay events during immobility-related sharp wave/ripples are also goal-directed, and therefore more aligned with theta sweeps than experience. Our findings indicate that hippocampal theta sweeps provide a neural substrate for online goal-directed spatial planning.

neuroscience↗

bioRxiv2025

Differential encoding of social identity, valence and unfamiliarity in the amygdala and piriform cortex

To appropriately respond to social situations, animals must rapidly identify conspecifics as individuals, gauge their familiarity and recall any good or bad associations. In previous work (Mazuski & OKeefe, 2022), we characterized populations of neurons in the basolateral amygdala complex (BLA) that were strongly tuned to social conspecifics. In this current study, we asked whether these or other populations in the BLA encode properties necessary for social interaction: individual recognition, familiarity detection and reward association. In addition to cells in the rat lateral amygdala (LA) and basolateral amygdala (BLA), we recorded from cells in the anatomically-related piriform cortex (PIR) to see how much of the amygdala response was inherited from this input. Here, we show that these three interrelated areas encode distinct features of social conspecifics at the population and single neuron level. We recorded from large populations of neurons using 4-shank Neuropixels probes while rats learned a social discrimination task, where one male conspecific was paired with a food reward (S+) and the other its absence (S-). For comparison, two unfamiliar animals were presented on occasional probe trials. After successful discrimination learning, we looked for transfer effects to our previously studied task where implanted rats freely interacted with all four conspecifics in an open-field environment. The LA dynamically encoded social reward learning. Initially, LA neuronal population activity could not distinguish between the S+ and S-conspecifics, but after learning distinct representations emerged. In contrast, the PIR showed no effect of social reward learning. Single PIR units encoded social identity with strong tuning to individual conspecifics both before and after learning. The BLA encoded both reward learning and social identity suggesting this is where the PIR and LA information streams converge. Unexpectedly, the BLA and LA strongly coded for the unfamiliarity of the rat - single neurons responded to the probe trial animals with firing rates 2-5x higher than to the task animals. This cross-region encoding of identity, reward and unfamiliarity was reactivated during social interaction in the new open-field environment, demonstrating that the learning was not context specific. The results throw light on how distinct neural circuits contribute to social recognition and memory and how they interact with each other.

neuroscience↗

bioRxiv2024

Isoprene deters insect herbivory by priming plant hormone responses

Isoprene, emitted by some plants, enhances plant abiotic resilience but its role in biotic stress resilience remains elusive. We used tobacco plants engineered to emit isoprene (IE) and the corresponding azygous non-emitting control (NE) to investigate isoprene emission and biotic stress resilience. IE plants were more resistant to insect herbivory than NE plants. Worms preferred to feed on NE rather than IE leaves. IE plants showed less decline in photosynthesis during worm feeding. Insect feeding increased jasmonate levels in IE leaves, suggesting isoprene-mediated priming of the jasmonic acid response. Wound-induced increase in isoprene emission corresponded with elevation of methyl-D-erythritol-4-phosphate pathway and Calvin-Benson cycle metabolites. The results highlight interactive functions of isoprene and jasmonic acid and advance our understanding of how isoprene emission enhances plant resilience.

plant biology↗

bioRxiv2024

Repix: reliable, reusable, versatile chronic Neuropixels implants using minimal components

Neuropixels probes represent the state-of-the-art for high-yield electrophysiology in neuroscience: the simultaneous recording of hundreds of neurons is now routinely carried out in head-restrained animals. In contrast, neural recording in unrestrained animals, as well as recording and tracking neurons over days, remains challenging, though it is possible using chronic implants. A major challenge is the availability of simple methods that can be implemented with limited or no prior experience with Neuropixels probes, while achieving reliable, reusable, versatile high-density electrophysiology. Here we developed, deployed, and evaluated the real-world performance of Repix, a chronic implantation system that permits the repeated re-use of Neuropixels probes. The lightweight system allows implanted animals to express a full range of natural behaviors, including social behaviors. We show that Repix allows the recording of hundreds of neurons across many months, up to a year, with implants across cortical and subcortical brain regions. Probes can be reused repeatedly with stable yield. Repix has been used by 16 researchers in 10 laboratories to date, and we evaluated the real-world performance of Repix in a variety of chronic recording paradigms in both mice and rats with a combined 209 implantations. We found that the key advantage of Repix is robustness and simplicity. Adopters of Repix became proficient at five procedures on average, regardless of prior experience with in vivo electrophysiology. With the companion protocol alongside this article, the performance and user-friendliness of Repix should facilitate a wide uptake of chronic Neuropixels recordings.

neuroscience↗

bioRxiv2022

The City Nature Challenge - A global citizen science phenomenon contributing to biodiversity knowledge and informing local government practices

The bioblitz phenomenon has recently branched into cities, presenting exciting opportunities for local governments to channel participants efforts toward local issues. The City Nature Challenge (CNC) is one such initiative that has been quickly uptaken by hundreds of municipalities worldwide. Despite high participation, we still lack a framework for evaluating how the CNC contributes to local biodiversity knowledge and to inform local government practices. Here, we develop such a tool and present a case study that illustrates its applicability. We demonstrate that the collected records contributed to a better understanding of contemporary, local biodiversity patterns and provided a more realistic representation of understudied groups such as insects and fungi. Importantly, we show that the CNC presented local governments with a cost-effective tool to make informed, evidence-based management and policy decisions, improve education and engagement programs, foster cross-council collaborations, and support a stronger sense of environmental stewardship within the local community.

scientific communication and education↗

bioRxiv2021

Basolateral Amygdala Represents and Remembers Ethological Events

The basolateral amygdala plays a crucial role in memory consolidation yet the general neural mechanism remains elusive. Basolateral amygdala neurons were recorded from freely-moving rats as they interacted with different ethological stimuli: male or female rats, a moving toy and food. Over 20% of neurons showed highly tuned event-specific responses to a single class of stimuli. Firing persisted in 30% of these responsive cells for minutes after the removal of the eliciting stimulus. Neural information flowed directionally from event-specific neurons to less specific neurons with changes in connection strength after removal of the stimulus. We propose that the basolateral amygdala identifies specific ethological events, with circuit-wide activity driven by the event-specific neurons during and after the termination of those events likely facilitating active short-term memory consolidation.

neuroscience↗

bioRxiv2021

Hippocampal place cells use vector computations to navigate

One function of the Hippocampal Cognitive Map is to provide information about salient locations in familiar environments such as those containing reward or danger, and to support navigation towards or away from those locations1. Although much is known about how the hippocampus encodes location in world-centred coordinates, how it supports flexible navigation is less well understood. We recorded from CA1 place cells while rats navigated to a goal or freely foraged on the honeycomb maze2. The maze tests the animals ability to navigate using indirect as well as direct paths to the goal and allows the directionality of place cells to be assessed at each choice point during traversal to the goal. Place fields showed strong directional polarization in the navigation task, and to a lesser extent during random foraging. This polarization was characterized by vector fields which converged to sinks distributed throughout the environment. The distribution of these convergence sinks was centred near the goal location, and the population vector field converged on the goal, providing a strong navigational signal. Changing the goal location led to the movement of ConSinks and vector fields towards the new goal and within-days, the ConSink distance to the goal decreased with continued training. The honeycomb maze allows the independent assessment of spatial representation and spatial action in place cell activity and shows how the latter depends on the former. The results suggest a vector-based model of how the hippocampus supports flexible navigation, allowing animals to select optimal paths to destinations from any location in the environment.

neuroscience↗

bioRxiv2020

Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings

To study the dynamics of neural processing across timescales, we require the ability to follow the spiking of thousands of individually separable neurons over weeks and months, during unrestrained behavior. To address this need, we introduce the Neuropixels 2.0 probe together with novel analysis algorithms. The new probe has over 5,000 sites and is miniaturized such that two probes plus a headstage, recording 768 sites at once, weigh just over 1 g, suitable for implanting chronically in small mammals. Recordings with high quality signals persisting for at least two months were reliably obtained in two species and six different labs. Improved site density and arrangement combined with new data processing methods enable automatic post-hoc stabilization of data despite brain movements during behavior and across days, allowing recording from the same neurons in the mouse visual cortex for over 2 months. Additionally, an optional configuration allows for recording from multiple sites per available channel, with a penalty to signal-to-noise ratio. These probes and algorithms enable stable recordings from >10,000 sites during free behavior in small animals such as mice.

neuroscience↗

bioRxiv2020

Two distinct types of eye-head coupling in freely moving mice

Animals actively interact with their environment to gather sensory information. There is conflicting evidence about how mice use vision to sample their environment. During head restraint, mice make rapid eye movements strongly coupled between the eyes, similar to conjugate saccadic eye movements in humans. However, when mice are free to move their heads, eye movement patterns are more complex and often non-conjugate, with the eyes moving in opposite directions. Here, we combined eye tracking with head motion measurements in freely moving mice and found that both observations can be explained by the existence of two distinct types of coupling between eye and head movements. The first type comprised non-conjugate eye movements which systematically compensated for changes in head tilt to maintain approximately the same visual field relative to the horizontal ground plane. The second type of eye movements were conjugate and coupled to head yaw rotation to produce a "saccade and fixate" gaze pattern. During head initiated saccades, the eyes moved together in the same direction as the head, but during subsequent fixation moved in the opposite direction to the head to compensate for head rotation. This "saccade and fixate" pattern is similar to that seen in humans who use eye movements (with or without head movement) to rapidly shift gaze but in mice relies on combined eye and head movements. Indeed, the two types of eye movements very rarely occurred in the absence of head movements. Even in head-restrained mice, eye movements were invariably associated with attempted head motion. Both types of eye-head coupling were seen in freely moving mice during social interactions and a visually-guided object tracking task. Our results reveal that mice use a combination of head and eye movements to sample their environment and highlight the similarities and differences between eye movements in mice and humans. HighlightsO_LITracking of eyes and head in freely moving mice reveals two types of eye-head coupling C_LIO_LIEye/head tilt coupling aligns gaze to horizontal plane C_LIO_LIRotational eye and head coupling produces a "saccade and fixate" gaze pattern with head leading the eye C_LIO_LIBoth types of eye-head coupling are maintained during visually-guided behaviors C_LIO_LIEye movements in head-restrained mice are related to attempted head movements C_LI

animal behavior and cognition↗

bioRxiv2018

An ultralight head-mounted camera system integrates detailed behavioral monitoring with multichannel electrophysiology in freely moving mice

Breakthroughs in understanding the neural basis of natural behavior require neural recording and intervention to be paired with high-fidelity multimodal behavioral monitoring. An extensive genetic toolkit for neural circuit dissection, and well-developed neural recording technology, make the mouse a powerful model organism for systems neuroscience. However, methods for high-bandwidth acquisition of behavioral signals in mice remain limited to fixed-position cameras and other off-animal devices, complicating the monitoring of animals freely engaged in natural behaviors. Here, we report the development of an ultralight head-mounted camera system combined with head-movement sensors to simultaneously monitor eye position, pupil dilation, whisking, and pinna movements along with head motion in unrestrained, freely behaving mice. The power of the combined technology is demonstrated by observations linking eye position to head orientation; whisking to non-tactile stimulation; and, in electrophysiological experiments, visual cortical activity to volitional head movements.

neuroscience↗