Central amygdala contributes to stimulus facilitation and pre-stimulus vigilance during cerebellar learning.

Our previous studies found that the central amygdala (CeA) modulates cerebellum-dependent eyeblink conditioning (EBC) using muscimol inactivation. We also found that CeA inactivation decreases cerebellar neuronal activity during the conditional stimulus (CS) from the start of training. Based on these findings, we hypothesized that the CeA facilitates CS input to the cerebellum. The current study tested the CS facilitation hypothesis using optogenetic inhibition with archaerhodopsin (Arch) and excitation with channelrhodopsin (ChR2) of the CeA during EBC in male rats. Optogenetic manipulations were administered during the 400 ms tone CS or during a 400 ms pre-CS period. As predicted by the CS facilitation hypothesis CeA inhibition during the CS impaired EBC and CeA excitation during the CS facilitated EBC. Unexpectedly, CeA inhibition just prior to the CS also impaired EBC, while CeA excitation during the pre-CS pathway did not facilitate EBC. The results suggest that the CeA contributes to CS facilitation and vigilance during the pre-CS period. These putative functions of the CeA may be mediated through separate output pathways from the CeA to the cerebellum.

Polar bear energetic and behavioral strategies on land with implications for surviving the ice-free period.

Declining Arctic sea ice is increasing polar bear land use. Polar bears on land are thought to minimize activity to conserve energy. Here, we measure the daily energy expenditure (DEE), diet, behavior, movement, and body composition changes of 20 different polar bears on land over 19-23 days from August to September (2019-2022) in Manitoba, Canada. Polar bears on land exhibited a 5.2-fold range in DEE and 19-fold range in activity, from hibernation-like DEEs to levels approaching active bears on the sea ice, including three individuals that made energetically demanding swims totaling 54-175 km. Bears consumed berries, vegetation, birds, bones, antlers, seal, and beluga. Beyond compensating for elevated DEE, there was little benefit from terrestrial foraging toward prolonging the predicted time to starvation, as 19 of 20 bears lost mass (0.4-1.7 kg•day-1). Although polar bears on land exhibit remarkable behavioral plasticity, our findings reinforce the risk of starvation, particularly in subadults, with forecasted increases in the onshore period.

Knockdown of the Non-canonical Wnt Gene Prickle2 Leads to Cerebellar Purkinje Cell Abnormalities While Cerebellar-Mediated Behaviors Remain Intact.

Autism spectrum disorders (ASD) involve brain wide abnormalities that contribute to a constellation of symptoms including behavioral inflexibility, cognitive dysfunction, learning impairments, altered social interactions, and perceptive time difficulties. Although a single genetic variation does not cause ASD, genetic variations such as one involving a non-canonical Wnt signaling gene, Prickle2, has been found in individuals with ASD. Previous work looking into phenotypes of Prickle2 knock-out (Prickle2-/-) and heterozygous mice (Prickle2-/+) suggest patterns of behavior similar to individuals with ASD including altered social interaction and behavioral inflexibility. Growing evidence implicates the cerebellum in ASD. As Prickle2 is expressed in the cerebellum, this animal model presents a unique opportunity to investigate the cerebellar contribution to autism-like phenotypes. Here, we explore cerebellar structural and physiological abnormalities in animals with Prickle2 knockdown using immunohistochemistry, whole-cell patch clamp electrophysiology, and several cerebellar-associated motor and timing tasks, including interval timing and eyeblink conditioning. Histologically, Prickle2-/- mice have significantly more empty spaces or gaps between Purkinje cells in the posterior lobules and a decreased propensity for Purkinje cells to fire action potentials. These structural cerebellar abnormalities did not impair cerebellar-associated behaviors as eyeblink conditioning and interval timing remained intact. Therefore, although Prickle-/- mice show classic phenotypes of ASD, they do not recapitulate the involvement of the adult cerebellum and may not represent the pathophysiological heterogeneity of the disorder.

Ancient bears provide insights into Pleistocene ice age refugia in Southeast Alaska.

During the Late Pleistocene, major parts of North America were periodically covered by ice sheets. However, there are still questions about whether ice-free refugia were present in the Alexander Archipelago along the Southeast (SE) Alaska coast during the last glacial maximum (LGM). Numerous subfossils have been recovered from caves in SE Alaska, including American black (Ursus americanus) and brown (U. arctos) bears, which today are found in the Alexander Archipelago but are genetically distinct from mainland bear populations. Hence, these bear species offer an ideal system to investigate long-term occupation, potential refugial survival and lineage turnover. Here, we present genetic analyses based on 99 new complete mitochondrial genomes from ancient and modern brown and black bears spanning the last ~45,000 years. Black bears form two SE Alaskan subclades, one preglacial and another postglacial, that diverged >100,000 years ago. All postglacial ancient brown bears are closely related to modern brown bears in the archipelago, while a single preglacial brown bear is found in a distantly related clade. A hiatus in the bear subfossil record around the LGM and the deep split of their pre- and postglacial subclades fail to support a hypothesis of continuous occupancy in SE Alaska throughout the LGM for either species. Our results are consistent with an absence of refugia along the SE Alaska coast, but indicate that vegetation quickly expanded after deglaciation, allowing bears to recolonize the area after a short-lived LGM peak.

Shaking up the silence: consequences of HMGN1 antagonizing PRC2 in the Down syndrome brain.

Intellectual disability is a well-known hallmark of Down Syndrome (DS) that results from the triplication of the critical region of human chromosome 21 (HSA21). Major studies were conducted in recent years to gain an understanding about the contribution of individual triplicated genes to DS-related brain pathology. Global transcriptomic alterations and widespread changes in the establishment of neural lineages, as well as their differentiation and functional maturity, suggest genome-wide chromatin organization alterations in trisomy. High Mobility Group Nucleosome Binding Domain 1 (HMGN1), expressed from HSA21, is a chromatin remodeling protein that facilitates chromatin decompaction and is associated with acetylated lysine 27 on histone H3 (H3K27ac), a mark correlated with active transcription. Recent studies causatively linked overexpression of HMGN1 in trisomy and the development of DS-associated B cell acute lymphoblastic leukemia (B-ALL). HMGN1 has been shown to antagonize the activity of the Polycomb Repressive Complex 2 (PRC2) and prevent the deposition of histone H3 lysine 27 trimethylation mark (H3K27me3), which is associated with transcriptional repression and gene silencing. However, the possible ramifications of the increased levels of HMGN1 through the derepression of PRC2 target genes on brain cell pathology have not gained attention. In this review, we discuss the functional significance of HMGN1 in brain development and summarize accumulating reports about the essential role of PRC2 in the development of the neural system. Mechanistic understanding of how overexpression of HMGN1 may contribute to aberrant brain cell phenotypes in DS, such as altered proliferation of neural progenitors, abnormal cortical architecture, diminished myelination, neurodegeneration, and Alzheimer's disease-related pathology in trisomy 21, will facilitate the development of DS therapeutic approaches targeting chromatin.

The dorsal hippocampus' role in context-based timing in rodents.

To act proactively, we must predict when future events will occur. Individuals generate temporal predictions using cues that indicate an event will happen after a certain duration elapses. Neural models of timing focus on how the brain represents these cue-duration associations. However, these models often overlook the fact that situational factors frequently modulate temporal expectations. For example, in realistic environments, the intervals associated with different cues will often covary due to a common underlying cause. According to the 'common cause hypothesis,' observers anticipate this covariance such that, when one cue's interval changes, temporal expectations for other cues shift in the same direction. Furthermore, as conditions will often differ across environments, the same cue can mean different things in different contexts. Therefore, updates to temporal expectations should be context-specific. Behavioral work supports these predictions, yet their underlying neural mechanisms are unclear. Here, we asked whether the dorsal hippocampus mediates context-based timing, given its broad role in context-conditioning. Specifically, we trained rats with either hippocampal or sham lesions that two cues predicted reward after either a short or long duration elapsed (e.g., tone-8 s/light-16 s). Then, we moved rats to a new context and extended the long cue's interval (e.g., light-32 s). This caused rats to respond later to the short cue, despite never being trained to do so. Importantly, when returned to the initial training context, sham rats shifted back toward both cues' original intervals. In contrast, lesion rats continued to respond at the long cue's newer interval. Surprisingly, they still showed contextual modulation for the short cue, responding earlier like shams. These data suggest the hippocampus only mediates context-based timing if a cue is explicitly paired and/or rewarded across distinct contexts. Furthermore, as lesions did not impact timing measures at baseline or acquisition for the long cue's new interval, our data suggests that the hippocampus only modulates timing when context is relevant.

Investigating the effect of phospholipids on droplet formation and surface property evolution in microfluidic devices for droplet interface bilayer (DIB) formation.

Despite growing interest in droplet microfluidic methods for droplet interface bilayer (DIB) formation, there is a dearth of information regarding how phospholipids impact device function. Limited characterization has been carried out for phospholipids, either computationally (in silico) or experimentally (in situ) in polydimethylsiloxane (PDMS) microfluidic devices, despite recent work providing a better understanding of how other surfactants behave in microfluidic systems. Hence, microfluidic device design for DIB applications relies heavily on trial and error, with many assumptions made about the impact of phospholipids on droplet formation and surface properties. Here, we examine the effects of phospholipids on interfacial tension, droplet formation, wetting, and hence device longevity, using DPhPC as the most widely used lipid for DIB formation. We use a customized COMSOL in silico model in comparison with in situ experimental data to establish that the stabilization of droplet formation seen when the lipid is dosed in the aqueous phase (lipid-in) or in the oil phase (lipid-out) is directly dependent on the effects of lipids on the device surface properties, rather than on how fast they coat the droplet. Furthermore, we establish a means to visually characterize surface property evolution in the presence of lipids and explore rates of device failure in the absence of lipid, lipid-out, and lipid-in. This first exploration of the effects of lipids on device function may serve to inform the design of microfluidic devices for DIB formation as well as to troubleshoot causes of device failure during microfluidic DIB experiments.

Insights into bear evolution from a Pleistocene polar bear genome.

The polar bear (Ursus maritimus) has become a symbol of the threat to biodiversity from climate change. Understanding polar bear evolutionary history may provide insights into apex carnivore responses and prospects during periods of extreme environmental perturbations. In recent years, genomic studies have examined bear speciation and population history, including evidence for ancient admixture between polar bears and brown bears (Ursus arctos). Here, we extend our earlier studies of a 130,000- to 115,000-y-old polar bear from the Svalbard Archipelago using a 10× coverage genome sequence and 10 new genomes of polar and brown bears from contemporary zones of overlap in northern Alaska. We demonstrate a dramatic decline in effective population size for this ancient polar bear's lineage, followed by a modest increase just before its demise. A slightly higher genetic diversity in the ancient polar bear suggests a severe genetic erosion over a prolonged bottleneck in modern polar bears. Statistical fitting of data to alternative admixture graph scenarios favors at least one ancient introgression event from brown bears into the ancestor of polar bears, possibly dating back over 150,000 y. Gene flow was likely bidirectional, but allelic transfer from brown into polar bear is the strongest detected signal, which contrasts with other published work. These findings may have implications for our understanding of climate change impacts: Polar bears, a specialist Arctic lineage, may not only have undergone severe genetic bottlenecks but also been the recipient of generalist, boreal genetic variants from brown bears during critical phases of Northern Hemisphere glacial oscillations.

Theta oscillations in rat infralimbic cortex are associated with the inhibition of cocaine seeking during extinction.

Infralimbic cortical (IL) manipulations indicate that this region mediates extinction learning and suppresses cocaine seeking following cocaine self-administration. However, little work has recorded IL activity during the inhibition of cocaine seeking due to the difficulty of determining precisely when cocaine-seeking behaviour is inhibited within a cocaine-seeking session. The present study used in vivo electrophysiology to examine IL activity across extinction as well as during cocaine self-administration and reinstatement. Sprague-Dawley rats underwent 6-h access cocaine self-administration in which the response lever was available during discrete signalled trials, a procedure which allowed for the comparison between epochs of cocaine seeking versus the inhibition thereof. Subsequently, rats underwent extinction and cocaine-primed reinstatement using the same procedure. Results indicate that theta rhythms (4-10 Hz) dominated IL local-field potential (LFP) activity during all experimental stages. During extinction, theta power fluctuated significantly surrounding the lever press and was lower when rats engaged in cocaine seeking versus when they withheld from doing so. These patterns of oscillatory activity differed from self-administration and reinstatement stages. Single-unit analyses indicate heterogeneity of IL unit responses, supporting the idea that multiple neuronal subpopulations exist within the IL and promote the expression of different and even opposing cocaine-seeking behaviours. Together, these results are consistent with the idea that aggregate synaptic and single-unit activity in the IL represent the engagement of the IL in action monitoring to promote adaptive behaviour in accordance with task contingencies and reveal critical insights into the relationship between IL activity and the inhibition of cocaine seeking.

A plug-and-play modular microcapillary platform for the generation of multicompartmental double emulsions using glass or fluorocarbon capillaries.

Although multiple emulsions have a wide range of applications in biology, medicine, chemistry and cosmetics, the use of microfluidic devices to generate them remains limited to specialist laboratories. This is because of the expertise required to design and operate these technologies. Here we show a plug-and-play microcapillary platform for the generation of multicompartmental double emulsions which only requires a low cost 3D printer for fabrication and syringe pumps for operation. Our microcapillary platform is modular because we fabricate junction boxes from a flexible resin to hold and align any type of standard glass capillary or piece of tubing for droplet formation without the need for capillary alignment. The flexible resin enables total sealing of the capillaries without the need for gaskets or adhesives, and the ability to use any type of capillary or tubing means that surface treatment is not required. We show how our microcapillary platform is able to generate water-in-oil-in-water, oil-in-water-in-oil, and oil-in-oil-in-water multicompartmental double emulsions with between 1 and 10 inner droplets with high accuracy and reproducibility using standard oils (FC40, mineral oil) and inexpensive surfactants (sodium dodecyl sulfate, SDS or 1H,1H,2H,2H-perfluoro-1-octanol, PFO). Additionally, we show the formation of binary multicompartmental double emulsions, where two types of inner phase droplets can be encapsulated in the multicompartmental emulsions. Our results demonstrate how simple and accessible tools can be employed to generate a powerful modular microcapillary platform. We anticipate that the simplicity of fabrication and operation of this platform, coupled with its ability to make a wide variety of different types of emulsions, will be attractive both to microfluidic laboratories and to those without microfluidic expertise who need an enabling tool for multicompartmental double emulsion formation.

Amygdala central nucleus modulation of cerebellar learning in female rats.

Previous studies found that inactivation of the central amygdala (CeA) severely impaired acquisition of cerebellum-dependent delay eye-blink conditioning (EBC) in male rats and rabbits. Sex differences in EBC and the effects of stress on EBC have been reported and might be related to sex differences in amygdala modulation of cerebellar learning. The current study examined the effects of CeA inactivation with muscimol on acquisition and retention of EBC in female rats. Like male rats, CeA inactivation in female rats severely impaired EBC acquisition and retention. Comparison of the female data with previously published data from males indicates no substantive sex differences in the effects of CeA inactivation on acquisition or retention of EBC. The results indicate that amygdala modulation of cerebellar learning is not sex-specific. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Amygdala central nucleus modulation of cerebellar learning with a visual conditioned stimulus.

Previous studies found that reversible inactivation of the central amygdala (CeA) severely impairs acquisition and retention of cerebellum-dependent eye-blink conditioning (EBC) with an auditory conditioned stimulus (CS). A monosynaptic pathway between the CeA and basilar pontine nuclei (BPN) may be capable of facilitating cerebellar learning. However, given that the CeA projects to the medial auditory thalamus, a critical part of the auditory CS pathway in EBC, the CeA influence on cerebellar learning could be specific to auditory stimuli. Here we examined the generality of CeA facilitation of EBC acquisition and retention in rats using a visual CS. As in our previous studies using an auditory CS, inactivation of the CeA with muscimol severely impaired acquisition and retention of EBC with a visual CS. Extending training to 15 100-trial sessions resulted in acquisition of EBC, indicating that the CeA plays a modulatory role in cerebellar learning and is not part of the necessary neural circuitry for EBC. Tract-tracing experiments verified that axons from the CeA reach both the BPN and medial auditory thalamus (part of the necessary auditory CS pathway), but were not found in the ventral lateral geniculate (part of the necessary visual CS pathway). The neuroanatomical results suggest that the CeA most likely modulates cerebellar learning through its projection to the BPN. The findings of the current study are consistent with the hypothesis that the CeA modulates cerebellar learning by increasing CS-related sensory input to the cerebellar cortex and interpositus nucleus via the BPN. This increase in CS-related input is thought to constitute an increase in attention to the CS during EBC.

The impact of concomitant pulmonary hypertension on early and late outcomes following surgery for mitral stenosis.

OBJECTIVES: To provide initial evidence on the management of mitral stenosis and pulmonary hypertension (PH) based on short-term and long-term outcomes following mitral valve surgery. METHODS: Consecutive patients with mitral stenosis (n = 317) who had undergone mitral valve surgery between 1992 and 2014 with recorded pulmonary artery pressure (PAP) data were reviewed. PH severity, based on systolic PAP, was categorized as mild (35 to 44 mm Hg), moderate (45 to 59 mm Hg), or severe (>60 mm Hg). Primary outcomes were 30-day mortality and long-term survival. RESULTS: There were no significant between-group differences in age or preoperative comorbidities. Mitral valve surgery included mitral valve replacement (78%) and repair (22%). The severe PH group had more mitral valve replacement (81%; P = .04), severe tricuspid valve regurgitation (31%; P = .003), right heart failure (17%; P = .02), and concomitant tricuspid valve procedures (46%; P < .001). For severe PH, 30-day mortality was 9%, with no significant group differences. Ten- and 12-year survival were significantly worse in the moderate-severe PH group (58% and 51%, respectively) compared with the normal PAP-mild PH group (83% and 79%, respectively) with a hazard ratio of 2.98 (95% confidence interval, 1.55-5.75; P = .001). Ten-year survival after mitral valve surgery for mitral stenosis was inversely associated with preoperative PAP. CONCLUSIONS: Mitral valve surgery can be performed with acceptable 30-day mortality for patients with mitral stenosis and moderate to severe PH, but long-term survival is impaired by moderate to severe PH. Patients with mitral stenosis and mild PH (systolic PAP 35-44 mm Hg) should be considered for mitral valve surgery.

Amygdala Modulation of Cerebellar Learning.

Previous studies showed that amygdala lesions or inactivation slow the acquisition rate of cerebellum-dependent eyeblink conditioning, a type of associative motor learning. The current study was designed to determine the behavioral nature of amygdala-cerebellum interactions, to identify the neural pathways underlying amygdala-cerebellum interactions, and to examine how the amygdala influences cerebellar learning mechanisms in rats. Pharmacological inactivation of the central amygdala (CeA) severely impaired acquisition and retention of eyeblink conditioning, indicating that the amygdala continues to interact with the cerebellum after conditioning is consolidated (Experiment 1). CeA inactivation also substantially reduced stimulus-evoked and learning-related neuronal activity in the cerebellar anterior interpositus nucleus during acquisition and retention of eyeblink conditioning (Experiment 2). A very small proportion of cerebellar neurons responded to the conditioned stimulus (CS) during CeA inactivation. Finally, retrograde and anterograde tracing experiments identified the basilar pontine nucleus at the confluence of outputs from CeA that may support amygdala modulation of CS input to the cerebellum (Experiment 3). Together, these results highlight a role for the CeA in the gating of CS-related input to the cerebellum during motor learning that is maintained even after the conditioned response is well learned. SIGNIFICANCE STATEMENT: The current study is the first to demonstrate that the amygdala modulates sensory-evoked and learning-related neuronal activity within the cerebellum during acquisition and retention of associative learning. The findings suggest a model of amygdala-cerebellum interactions in which the amygdala gates conditioned stimulus inputs to the cerebellum through a direct projection from the medial central nucleus to the basilar pontine nucleus. Amygdala gating of sensory input to the cerebellum may be an attention-like mechanism that facilitates cerebellar learning. In contrast to previous theories of amygdala-cerebellum interactions, the sensory gating hypothesis posits that the gating mechanism continues to be necessary for retrieval of cerebellar memory after learning is well established.

Impacts of Human Recreation on Brown Bears (Ursus arctos): A Review and New Management Tool.

Increased popularity of recreational activities in natural areas has led to the need to better understand their impacts on wildlife. The majority of research conducted to date has focused on behavioral effects from individual recreations, thus there is a limited understanding of the potential for population-level or cumulative effects. Brown bears (Ursus arctos) are the focus of a growing wildlife viewing industry and are found in habitats frequented by recreationists. Managers face difficult decisions in balancing recreational opportunities with habitat protection for wildlife. Here, we integrate results from empirical studies with expert knowledge to better understand the potential population-level effects of recreational activities on brown bears. We conducted a literature review and Delphi survey of brown bear experts to better understand the frequencies and types of recreations occurring in bear habitats and their potential effects, and to identify management solutions and research needs. We then developed a Bayesian network model that allows managers to estimate the potential effects of recreational management decisions in bear habitats. A higher proportion of individual brown bears in coastal habitats were exposed to recreation, including photography and bear-viewing than bears in interior habitats where camping and hiking were more common. Our results suggest that the primary mechanism by which recreation may impact brown bears is through temporal and spatial displacement with associated increases in energetic costs and declines in nutritional intake. Killings in defense of life and property were found to be minimally associated with recreation in Alaska, but are important considerations in population management. Regulating recreation to occur predictably in space and time and limiting recreation in habitats with concentrated food resources reduces impacts on food intake and may thereby, reduce impacts on reproduction and survival. Our results suggest that decisions managers make about regulating recreational activities in time and space have important consequences for bear populations. The Bayesian network model developed here provides a new tool for managers to balance demands of multiple recreational activities while supporting healthy bear populations.

Immobilization of grizzly bears (Ursus arctos) with dexmedetomidine, tiletamine, and zolazepam.

Safe and effective immobilization of grizzly bears (Ursus arctos) is essential for research and management. Fast induction of anesthesia, maintenance of healthy vital rates, and predictable recoveries are priorities. From September 2010 to May 2012, we investigated these attributes in captive and wild grizzly bears anesthetized with a combination of a reversible α2 agonist (dexmedetomidine [dexM], the dextrorotatory enantiomer of medetomidine) and a nonreversible N-methyl-d-aspartate (NMDA) agonist and tranquilizer (tiletamine and zolazepam [TZ], respectively). A smaller-than-expected dose of the combination (1.23 mg tiletamine, 1.23 mg zolazepam, and 6.04 µg dexmedetomidine per kg bear) produced reliable, fast ataxia (3.7 ± 0.5 min, x̄±SE) and workable anesthesia (8.1 ± 0.6 min) in captive adult grizzly bears. For wild bears darted from a helicopter, a dose of 2.06 mg tiletamine, 2.06 mg zolazepam, and 10.1 µg dexmedetomidine/kg produced ataxia in 2.5 ± 0.3 min and anesthesia in 5.5 ± 1.0 min. Contrary to published accounts of bear anesthesia with medetomidine, tiletamine, and zolazepam, this combination did not cause hypoxemia or hypoventilation, although mild bradycardia (<50 beats per min) occurred in most bears during the active season. With captive bears, effective dose rates during hibernation were approximately half those during the active season. The time to first signs of recovery after the initial injection of dexMTZ was influenced by heart rate (P<0.001) and drug dose (P<0.001). Intravenous (IV) injection of the reversal agent, atipamezole, significantly decreased recovery time (i.e., standing on all four feet and reacting to the surrounding environment) relative to intramuscular injection. Recovery times (25 ± 8 min) following IV injections of the recommended dose of atipamezole (10 µg/µg of dexmedetomidine) and half that dose (5 µg/µg) did not differ. However, we recommend use of the full dose based on the appearance of a more complete recovery. Field trials confirmed that the dexMTZ + atipamezole protocol is safe, reliable, and predictable when administered to wild grizzly bears, especially during helicopter capture operations.

Sampling designs matching species biology produce accurate and affordable abundance indices.

Wildlife biologists often use grid-based designs to sample animals and generate abundance estimates. Although sampling in grids is theoretically sound, in application, the method can be logistically difficult and expensive when sampling elusive species inhabiting extensive areas. These factors make it challenging to sample animals and meet the statistical assumption of all individuals having an equal probability of capture. Violating this assumption biases results. Does an alternative exist? Perhaps by sampling only where resources attract animals (i.e., targeted sampling), it would provide accurate abundance estimates more efficiently and affordably. However, biases from this approach would also arise if individuals have an unequal probability of capture, especially if some failed to visit the sampling area. Since most biological programs are resource limited, and acquiring abundance data drives many conservation and management applications, it becomes imperative to identify economical and informative sampling designs. Therefore, we evaluated abundance estimates generated from grid and targeted sampling designs using simulations based on geographic positioning system (GPS) data from 42 Alaskan brown bears (Ursus arctos). Migratory salmon drew brown bears from the wider landscape, concentrating them at anadromous streams. This provided a scenario for testing the targeted approach. Grid and targeted sampling varied by trap amount, location (traps placed randomly, systematically or by expert opinion), and traps stationary or moved between capture sessions. We began by identifying when to sample, and if bears had equal probability of capture. We compared abundance estimates against seven criteria: bias, precision, accuracy, effort, plus encounter rates, and probabilities of capture and recapture. One grid (49 km(2) cells) and one targeted configuration provided the most accurate results. Both placed traps by expert opinion and moved traps between capture sessions, which raised capture probabilities. The grid design was least biased (-10.5%), but imprecise (CV 21.2%), and used most effort (16,100 trap-nights). The targeted configuration was more biased (-17.3%), but most precise (CV 12.3%), with least effort (7,000 trap-nights). Targeted sampling generated encounter rates four times higher, and capture and recapture probabilities 11% and 60% higher than grid sampling, in a sampling frame 88% smaller. Bears had unequal probability of capture with both sampling designs, partly because some bears never had traps available to sample them. Hence, grid and targeted sampling generated abundance indices, not estimates. Overall, targeted sampling provided the most accurate and affordable design to index abundance. Targeted sampling may offer an alternative method to index the abundance of other species inhabiting expansive and inaccessible landscapes elsewhere, provided their attraction to resource concentrations.

Polar and brown bear genomes reveal ancient admixture and demographic footprints of past climate change.

Polar bears (PBs) are superbly adapted to the extreme Arctic environment and have become emblematic of the threat to biodiversity from global climate change. Their divergence from the lower-latitude brown bear provides a textbook example of rapid evolution of distinct phenotypes. However, limited mitochondrial and nuclear DNA evidence conflicts in the timing of PB origin as well as placement of the species within versus sister to the brown bear lineage. We gathered extensive genomic sequence data from contemporary polar, brown, and American black bear samples, in addition to a 130,000- to 110,000-y old PB, to examine this problem from a genome-wide perspective. Nuclear DNA markers reflect a species tree consistent with expectation, showing polar and brown bears to be sister species. However, for the enigmatic brown bears native to Alaska's Alexander Archipelago, we estimate that not only their mitochondrial genome, but also 5-10% of their nuclear genome, is most closely related to PBs, indicating ancient admixture between the two species. Explicit admixture analyses are consistent with ancient splits among PBs, brown bears and black bears that were later followed by occasional admixture. We also provide paleodemographic estimates that suggest bear evolution has tracked key climate events, and that PB in particular experienced a prolonged and dramatic decline in its effective population size during the last ca. 500,000 years. We demonstrate that brown bears and PBs have had sufficiently independent evolutionary histories over the last 4-5 million years to leave imprints in the PB nuclear genome that likely are associated with ecological adaptation to the Arctic environment.

Reevaluating hippocampus-dependent learning in FVB/N mice.

The FVB/N (FVB) mouse has been a popular background strain for constructing transgenic mice. However, behavioral phenotyping of the resultant mice is complicated, due to severe visual impairment in the FVB background strain. Previous studies reported cognitive impairments with the FVB strain, suggesting the background as unsuitable for behavioral analysis. In this study, we compared FVB mice to the well-characterized C57BL/6 (B6) strain in a battery of hippocampus-dependent tasks that had several nonvisual cues. The tasks included: trace eyeblink conditioning, spontaneous alternation in the Y maze, social recognition, trace and contextual fear conditioning, and odor habituation-dishabituation. FVB mice were able to learn all the tasks, often to similar levels as B6 mice. In contrast to previous reports, our data suggest FVB mice are not cognitively deficient with temporal memory tasks, when the tasks do not rely heavily upon vision. Thus, the FVB strain may be used as the genetic background for behavioral phenotyping when nonvisual hippocampal-dependent tasks are utilized.