Spatial Risk Effects From Lions Compound Impacts of Prey Depletion on African Wild Dogs.

Prey depletion threatens many carnivore species across the world and can especially threaten low-density subordinate competitors, particularly if subordinates are limited to low densities by their dominant competitors. Understanding the mechanisms that drive responses of carnivore density to prey depletion is not only crucial for conservation but also elucidates the balance between top-down and bottom-up limitations within the large carnivore guild. To avoid predation, competitively subordinate African wild dogs typically avoid their dominant competitors (lions) and the prey rich areas they are associated with, but no prior research has tested whether this pattern persists in ecosystems with anthropogenically-reduced prey density, and reduced lion density as a result.

FDA experiences with a centralized statistical monitoring tool.

The U.S. Food and Drug Administration (FDA) has broadly supported quality by design initiatives for clinical trials - including monitoring and data validation - by releasing two related guidance documents (FDA 2013 and 2019).

Control of feeding by a bottom-up midbrain-subthalamic pathway.

Investigative exploration and foraging leading to food consumption have vital importance, but are not well-understood. Since GABAergic inputs to the lateral and ventrolateral periaqueductal gray (l/vlPAG) control such behaviors, we dissected the role of vgat-expressing GABAergic l/vlPAG cells in exploration, foraging and hunting. Here, we show that in mice vgat l/vlPAG cells encode approach to food and consumption of both live prey and non-prey foods.

GABAergic CA1 neurons are more stable following context changes than glutamatergic cells.

The CA1 region of the hippocampus contains both glutamatergic pyramidal cells and GABAergic interneurons. Numerous reports have characterized glutamatergic CAMK2A cell activity, showing how these cells respond to environmental changes such as local cue rotation and context re-sizing. Additionally, the long-term stability of spatial encoding and turnover of these cells across days is also well-characterized.

Sparse genetically defined neurons refine the canonical role of periaqueductal gray columnar organization.

During threat exposure, survival depends on defensive reactions. Prior works linked large glutamatergic populations in the midbrain periaqueductal gray (PAG) to defensive freezing and flight, and established that the overarching functional organization axis of the PAG is along anatomically-defined columns. Accordingly, broad activation of the dorsolateral column induces flight, while activation of the lateral or ventrolateral (l and vl) columns induces freezing.

Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats.

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape vigor from innate and conditioned threats. Cholecystokinin (cck)-expressing cells in the hypothalamic dorsal premammillary nucleus (PMd) are necessary for initiating escape from innate threats via a projection to the dorsolateral periaqueductal gray (dlPAG).

Dorsal periaqueductal gray ensembles represent approach and avoidance states.

Animals must balance needs to approach threats for risk assessment and to avoid danger. The dorsal periaqueductal gray (dPAG) controls defensive behaviors, but it is unknown how it represents states associated with threat approach and avoidance. We identified a dPAG threatavoidance ensemble in mice that showed higher activity farther from threats such as the open arms of the elevated plus maze and a predator.

Shared Dorsal Periaqueductal Gray Activation Patterns during Exposure to Innate and Conditioned Threats.

The brainstem dorsal periaqueductal gray (dPAG) has been widely recognized as being a vital node orchestrating the responses to innate threats. Intriguingly, recent evidence also shows that the dPAG mediates defensive responses to fear conditioned contexts. However, it is unknown whether the dPAG displays independent or shared patterns of activation during exposure to innate and conditioned threats.

Coordination of escape and spatial navigation circuits orchestrates versatile flight from threats.

Naturalistic escape requires versatile context-specific flight with rapid evaluation of local geometry to identify and use efficient escape routes. It is unknown how spatial navigation and escape circuits are recruited to produce context-specific flight. Using mice, we show that activity in cholecystokinin-expressing hypothalamic dorsal premammillary nucleus (PMd-cck) cells is sufficient and necessary for context-specific escape that adapts to each environment's layout.

Response of lion demography and dynamics to the loss of preferred larger prey.

Large carnivores are experiencing range contraction and population declines globally. Prey depletion due to illegal offtake is considered a major contributor, but the effects of prey depletion on large carnivore demography are rarely tested. We measured African lion density and tested the factors that affect survival using mark-recapture models fit to six years of data from known individuals in Kafue National Park (KNP), Zambia.

Stimulation of the right entorhinal white matter enhances visual memory encoding in humans.

Background: While deep brain stimulation has been successful in treating movement disorders, such as in Parkinson's disease, its potential application in alleviating memory disorders is inconclusive.

Objective/hypothesis: We investigated the role of the location of the stimulating electrode on memory improvement and hypothesized that entorhinal white versus gray matter stimulation would have differential effects on memory.

Methods: Intracranial electrical stimulation was applied to the entorhinal area of twenty-two participants with already implanted electrodes as they completed visual memory tasks.

To Approach or Avoid: An Introductory Overview of the Study of Anxiety Using Rodent Assays.

Anxiety is a widely studied phenomenon in behavioral neuroscience, but the recent literature lacks an overview of the major conceptual framework underlying anxiety research to introduce young researchers to the field. In this mini-review article, which is aimed toward new undergraduate and graduate students, we discuss how researchers exploit the approach-avoidance conflict, an internal conflict rodents face between exploration of novel environments and avoidance of danger, to inform rodent assays that allow for the measurement of anxiety-related behavior in the laboratory. We review five widely-used rodent anxiety assays, consider the pharmacological validity of these assays, and discuss neural circuits that have recently been shown to modulate anxiety using the assays described.

Long-Term Characterization of Hippocampal Remapping during Contextual Fear Acquisition and Extinction.

Hippocampal CA1 place cell spatial maps are known to alter their firing properties in response to contextual fear conditioning, a process called "remapping." In the present study, we use chronic calcium imaging to examine remapping during fear retrieval and extinction of an inhibitory avoidance task in mice of both sexes over an extended period of time and with thousands of neurons. We demonstrate that hippocampal ensembles encode space at a finer scale following fear memory acquisition.

Do protection gradients explain patterns in herbivore densities? An example with ungulates in Zambia's Luangwa Valley.

Ungulate populations face declines across the globe, and populations are commonly conserved by using protected areas. However, assessing the effectiveness of protected areas in conserving ungulate populations has remained difficult. Using herd size data from four years of line transect surveys and distance sampling models, we modeled population densities of four important herbivore species across a gradient of protection on the edge of Zambia's South Luangwa National Park (SLNP) while accounting for the role of various ecological and anthropogenic variables.

Comparing methods for clinical investigator site inspection selection: a comparison of site selection methods of investigators in clinical trials.

During the past two decades, the number and complexity of clinical trials have risen dramatically increasing the difficulty of choosing sites for inspection. FDA's resources are limited and so sites should be chosen with care. To determine if data mining techniques and/or unsupervised statistical monitoring can assist with the process of identifying potential clinical sites for inspection.

Reduced higher dimensional temporal dynamism in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a common single gene disorder resulting in multi-organ involvement. In addition to physical manifestations such as characteristic pigmentary changes, nerve sheath tumors, and skeletal abnormalities, NF1 is also associated with increased rates of learning disabilities, attention deficit hyperactivity disorder, and autism spectrum disorder. While there are established NF1-related structural brain anomalies, including brain overgrowth and white matter disruptions, little is known regarding patterns of functional connectivity in NF1.

A Comparison of Pediatric and Adult Safety Studies for Antipsychotic and Antidepressant Drugs Submitted to the United States Food and Drug Administration.

Objective: To examine the differences in the adverse drug reaction (ADR) profile of antipsychotic and antidepressant agents between pediatric and adult patients in studies submitted to the Food and Drug Administration (FDA) during the drug development process.

Study Design: Clinical trials in adult and pediatric patients were conducted by sponsors as part of the drug development programs for antipsychotic and antidepressant agents, and ADR information was collected as part of those trials and submitted to the FDA. Data collection was conducted by reviewing publicly available FDA-authored reviews and FDA-approved product labels for 10 drugs with an antipsychotic or an antidepressant indication from 2007 to 2017.

Foraging investment in a long-lived herbivore and vulnerability to coursing and stalking predators.

Allocating resources to growth and reproduction requires grazers to invest time in foraging, but foraging promotes dental senescence and constrains expression of proactive antipredator behaviors such as vigilance. We explored the relationship between carnivore prey selection and prey foraging effort using incisors collected from the kills of coursing and stalking carnivores. We predicted that prey investing less effort in foraging would be killed more frequently by coursers, predators that often exploit physical deficiencies.

Primary Endpoints in Pediatric Efficacy Trials Submitted to the US FDA.

The selection of appropriate endpoints in pediatric drug development trials is a critical aspect of trial design. Given the high pediatric trial failure rate, selecting optimal trial design elements, such as the primary efficacy endpoint, is essential to ensuring increased potential for trial success. The objectives of this study were to identify the primary efficacy endpoints measured in pediatric drug development trials submitted to the US Food and Drug Administration and to relate endpoint attributes to trial and label outcome.

Theta Oscillations in the Human Medial Temporal Lobe during Real-World Ambulatory Movement.

The theta rhythm-a slow (6-12 Hz) oscillatory component of the local field potential-plays a critical role in spatial navigation and memory by coordinating the activity of neuronal ensembles within the medial temporal lobe (MTL). Although theta has been extensively studied in freely moving rodents, its presence in humans has been elusive and primarily investigated in stationary subjects. Here we used a unique clinical opportunity to examine theta within the human MTL during untethered, real-world ambulatory movement.

Theta-burst microstimulation in the human entorhinal area improves memory specificity.

The hippocampus is critical for episodic memory, and synaptic changes induced by long-term potentiation (LTP) are thought to underlie memory formation. In rodents, hippocampal LTP may be induced through electrical stimulation of the perforant path. To test whether similar techniques could improve episodic memory in humans, we implemented a microstimulation technique that allowed delivery of low-current electrical stimulation via 100 -diameter microelectrodes.

The relationship between direct predation and antipredator responses: a test with multiple predators and multiple prey.

Most species adjust their behavior to reduce the likelihood of predation. Many experiments have shown that antipredator responses carry energetic costs that can affect growth, survival, and reproduction, so that the total cost of predation depends on a trade-off between direct predation and risk effects. Despite these patterns, few field studies have examined the relationship between direct predation and the strength of antipredator responses, particularly for complete guilds of predators and prey.

Effects of a protection gradient on carnivore density and survival: an example with leopards in the Luangwa valley, Zambia.

Human activities on the periphery of protected areas can limit carnivore populations, but measurements of the strength of such effects are limited, largely due to difficulties of obtaining precise data on population density and survival. We measured how density and survival rates of a previously unstudied leopard population varied across a gradient of protection and evaluated which anthropogenic activities accounted for observed patterns. Insights into this generalist's response to human encroachment are likely to identify limiting factors for other sympatric carnivore species.