A multi-organ map of the human immune system across age, sex and ethnicity.

Understanding tissue biology's heterogeneity is crucial for advancing precision medicine. Despite the centrality of the immune system in tissue homeostasis, a detailed and comprehensive map of immune cell distribution and interactions across human tissues and demographics remains elusive. To fill this gap, we harmonised data from 12,981 single-cell RNA sequencing samples and curated 29 million cells from 45 anatomical sites to create a comprehensive compositional and transcriptional healthy map of the healthy immune system. We used this resource and a novel multilevel modelling approach to track immune ageing and test differences across sex and ethnicity. We uncovered conserved and tissue-specific immune-ageing programs, resolved sex-dependent differential ageing and identified ethnic diversity in clinically critical immune checkpoints. This study provides a quantitative baseline of the immune system, facilitating advances in precision medicine. By sharing our immune map, we hope to catalyse further breakthroughs in cancer, infectious disease, immunology and precision medicine.

Optimizing the Use of Semiochemical-Based Traps for Efficient Monitoring of Popillia japonica (Coleoptera: Scarabaeidae): Validation of a Volumetric Approach.

Japanese beetle, Popillia japonica Newman, is an invasive insect, native to Japan. The species was detected in the United States in New Jersey in 1916, and then first confirmed in Minnesota in 1968. Since their arrival, P. japonica has become a major pest in turfgrass and several crop agroecosystems. As P. japonica continues to spread throughout the U.S., it's important to discover more efficient ways to monitor adult populations. In 2018-2020, due to the high volume of P. japonica beetles collected in traps, a comparison of weight and volume calibration methods was conducted in Minnesota. Each method yielded a strong goodness of fit with counts of beetles captured. However, with a goal of cost-effective use of traps and in-field estimates, the volume-based approach was the preferred, most efficient method. In addition, a comparison of monitoring systems was conducted to observe differences in trap type, lure age, and check interval. Results from these studies indicate a standard green/yellow trap, and multi-component, semiochemical-based lure used for the duration of the P. japonica flight period, and a weekly check interval will minimize sampling time and resources, while providing accurate population estimates. In addition, results from these studies will benefit growers and researchers as they continue to explore integrated pest management (IPM) strategies for P. japonica. More importantly, by reducing the time required to quantify trap catches and rebait traps, these results may also facilitate area-wide tracking of P. japonica populations in newly invaded regions.

A degree-day model for forecasting adult phenology of Popillia japonica (Coleoptera: Scarabaeidae) in a temperate climate.

Japanese beetle, Popillia japonica (Newman), was first detected in the United States in New Jersey in 1916. The beetle gradually spread to the Midwest U.S. region, and was first confirmed in Minnesota in the late 1960's. Popillia japonica has subsequently become a major invasive insect pest in turfgrass and several agricultural crops. As P. japonica continues to spread throughout the U.S., and other countries, it is important to develop efficient ways to monitor adult populations, and where possible, forecast the phenology of adult population dynamics. During 2019-2021, field trials were conducted to develop a degree-day model that can be used to forecast P. japonica adult phenology under Minnesota, and Midwest summer climatic conditions in. We used commercially available traps and lures to monitor adult flight phenology, specifically beetle trap-catch, along with weather data at four locations in Minnesota, to relate ambient field temperatures to population phenology. The concordance correlation coefficient (CCC), an index of both precision and accuracy, was used to develop a final degree-day model. Model development included evaluation of simple and sine-wave degree-day calculation methods, start dates between 1 Jan. and 1 April, and a range of lower (0-15 °C) and upper (20-37 °C) thresholds. The optimum model was found to be a simple degree-day calculation, using a biofix date of 1 Jan, and lower and upper thresholds of 15 and 21.7 °C, respectively, for predicting 10% beetle trap-catch. The model will aid in future integrated pest management (IPM) and regulatory strategies by providing a tool for prediction of P. japonica adult flight phenology.

Long-term follow-up on bilateral posterior hypothalamic deep brain stimulation for treating refractory aggressive behavior in a patient with Cri du chat syndrome: analysis of clinical data, intraoperative microdialysis, and imaging connectomics

Posterior hypothalamic-deep brain stimulation (pHyp-DBS) has been reported as a successful treatment for reducing refractory aggressive behaviors in patients with distinct primary diagnoses. Here, we report on a patient with cri du chat syndrome presenting severe self-injury and aggressive behaviors toward others, who was treated with pHyp-DBS. Positive results were observed at long-term follow-up in aggressive behavior and quality of life. Intraoperative microdialysis and imaging connectomics analysis were performed to investigate possible mechanisms of action. Our results suggest the involvement of limbic and motor areas and alterations in main neurotransmitter levels in the targeted area that are associated with positive results following treatment.

Partial Budget Analysis of Exclusion Netting and Organic-certified Insecticides for Management of Spotted-wing Drosophila (Diptera: Drosophilidae) on Small Farms in the Upper Midwest.

Drosophila suzukii Matsumura (Diptera: Drosophilidae), or spotted-wing drosophila, is an invasive pest first detected in the United States in 2008. Although D. suzukii can use many cultivated fruit as hosts, raspberries are considered 'most at risk' for infestation. Conventional broad-spectrum insecticides are proven effective D. suzukii controls and can be economically profitable when combined with integrated pest management (IPM) on large-scale commercial raspberry farms. It remains unclear, however, whether organic controls are cost-effective strategies, particularly for farms operating on a small-scale seasonal basis, as is common in the Upper Midwest. The purpose of this paper is to explore the efficacy of two organic D. suzukii controls-exclusion netting for high tunnels and organic insecticides for open plots using data available from different field trials-and to ascertain whether any economic benefits of the organic controls outweigh treatment costs for small-scale raspberry operations under different risk scenarios. The field trials suggest that the organic treatments are effective controls for D. suzukii infestation and economically profitable. The exclusion netting treatment produced positive net returns compared to the alternative of no treatment and economically outperformed the organic-certified insecticide treatment for several yield, price and infestation scenarios. As D. suzukii infestation rates increased, net returns improved for both organic treatments. The economic results were robust across a range of yields and prices, suggesting that in almost all scenarios small scale organic raspberry growers benefit economically from the application of exclusion netting on high tunnels and insecticides for open plots.

Effects of Starvation, Age, and Mating Status on Flight Capacity of Laboratory-Reared Brown Marmorated Stink Bug (Hemiptera: Pentatomidae).

The brown marmorated stink bug, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), is an invasive species to North America and has spread throughout most of the territory. Understanding flight in H. halys is crucial to understanding the dispersal capacity and developing forecasting models for this pest. The purpose of this research was to assess the effects of starvation, age, mating status, sex, and preflight weight on flight parameters of laboratory-reared H. halys using computer-monitored flight mills. The mean flight distance observed over a 24-h period was 266 m and the maximum distance was 7.3 km. Overall, the flight capacity of males and females was similar, even though females weighed more than males. The proportion of H. halys that initiated flight was not affected by starvation, age, or mating status. The number of bouts of individual flights and velocity significantly increased with longer durations of starvation. The number of bouts significantly decreased with increasing age. The total distance flew and total flight time was not affected by starvation, age, or mating status. Although some statistical differences were seen across the experiments, these differences likely represent minimal ecological significance. Therefore, these results suggest that H. halys are remarkably resilient, which may contribute to their success as an invasive species. The findings of this study could help better predict the dispersal potential of H. halys in Minnesota.

Sweet Corn Sentinel Monitoring for Lepidopteran Field-Evolved Resistance to Bt Toxins.

As part of an insect resistance management plan to preserve Bt transgenic technology, annual monitoring of target pests is mandated to detect susceptibility changes to Bt toxins. Currently Helicoverpa zea (Boddie) monitoring involves investigating unexpected injury in Bt crop fields and collecting larvae from non-Bt host plants for laboratory diet bioassays to determine mortality responses to diagnostic concentrations of Bt toxins. To date, this monitoring approach has not detected any significant change from the known range of baseline susceptibility to Bt toxins, yet practical field-evolved resistance in H. zea populations and numerous occurrences of unexpected injury occur in Bt crops. In this study, we implemented a network of 73 sentinel sweet corn trials, spanning 16 U.S. states and 4 Canadian provinces, for monitoring changes in H. zea susceptibility to Cry and Vip3A toxins by measuring differences in ear damage and larval infestations between isogenic pairs of non-Bt and Bt hybrids over three years. This approach can monitor susceptibility changes and regional differences in other ear-feeding lepidopteran pests. Temporal changes in the field efficacy of each toxin were evidenced by comparing our current results with earlier published studies, including baseline data for each Bt trait when first commercialized. Changes in amount of ear damage showed significant increases in H. zea resistance to Cry toxins and possibly lower susceptibility to Vip3a. Our findings demonstrate that the sentinel plot approach as an in-field screen can effectively monitor phenotypic resistance and document field-evolved resistance in target pest populations, improving resistance monitoring for Bt crops.

Morphometric criteria to differentiate Drosophila suzukii (Diptera: Drosophilidae) seasonal morphs.

Temperate insect species often enter diapause in preparation for overwintering. One such species is the invasive vinegar fly, Drosophila suzukii (Matsumura), which has seasonal polymorphisms, considered winter and summer morphs. To date, the morphs have been differentiated by color and size with winter morphs typically being darker and larger compared to summer morphs. 'Dark' and 'large' are subjective, however, and standardizing an identification process can ensure that the morph of interest is being accurately characterized. The goal of our research was to investigate a quantitative method to distinguish between D. suzukii morphs based on body and wing size. We reared winter and summer morph D. suzukii in the laboratory using standard procedures, and measured wing length, wing width, and hind tibia length. Additionally, we collected field D. suzukii to document the seasonal phenology of the morphs in Minnesota based on our model's cutoff criteria. A classification and regression tree analysis were used to determine which metrics would be best for predicting field-caught D. suzukii morphs. Using laboratory-reared flies as our known morphs for the training data in the classification model we developed classification trees based on wing length and the ratio of wing length to hind tibia length. The frequency of winter and summer morphs present in the field varied based on which classification tree was used. Nevertheless, we suggest ratio of wing length to hind tibia length as the most robust criteria for differentiating D. suzukii morphs because the ratio accounts for the size variability between laboratory-reared and field-caught flies and the error rate of misclassification is reduced to 0.01 for males. The results from this work can aid in future D. suzukii research by allowing scientists to objectively differentiate the morphs, and thereby improve our understanding of the biology and phenology of seasonal morph dynamics.

Wave nature of conduction electrons in amorphous Co90Sc10 and Fe90Sc10 alloys.

The resistivity of amorphous Fe90Sc10 and Co90Sc10 alloys can be described well in terms of a simple model based on the wave character of electrons and their associated tunnelling over the temperature ranges ~1.9 K to 135 K and ~1.9 K to 12 K respectively. The extended range of agreement between experiment and theory for amorphous Fe90Sc10 is linked with its relatively small mean free path of [Formula: see text] = 0.32 nm, thus allowing electron waves to tunnel between clusters. On the other hand the restricted region of tunnelling of electron waves for amorphous Co90Sc10 alloys is linked with its relatively large mean free path of [Formula: see text] = 0.48 nm which restricts the ability for tunnelling between clusters while enabling electron waves to tunnel between different regions with a cluster.

Effects of Diapause on Halyomorpha halys (Hemiptera: Pentatomidae) Cold Tolerance.

Diapause and cold tolerance can profoundly affect the distribution and activity of temperate insects. Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), an alien invasive species from Asia, enters a winter dormancy in response to environmental cues. We investigated the nature of this dormancy and its effects on H. halys cold tolerance, as measured by supercooling points, lower lethal temperatures, and overwintering field mortality. Dormancy was induced by rearing individuals in the laboratory or under field conditions. We confirmed H. halys dormancy to be a state of diapause and not quiescence, and the life stage sensitive to diapause-inducing cues is between the second and fifth instar. In the laboratory, supercooling points of diapausing adults reached significantly lower temperatures than nondiapausing adults, but only when given enough time after imaginal ecdysis. Supercooling points of diapausing adults in overwintering microhabitats also decreased over time. Diapause increased adult survival after acute cold exposure in the laboratory and prolonged cold exposure in the field. Following diapause induction in the laboratory, changes to temperature and photoperiod had no significant effect on lower lethal temperatures and changes to photoperiod had no effect on supercooling points. Additionally, induction of diapause in the laboratory did not result in significantly different cold tolerance than natural field induction of diapause. This work demonstrates that H. halys diapause confers greater cold tolerance than a nondiapausing state and likely improves the probability of successful overwintering in some temperate climates. Hence, knowledge of diapause status could be used to refine forecasts of H. halys overwintering field mortality.

Electrical resistivity and wave character of free electrons in amorphous and nanoglass Sc75Fe25.

The residual electrical resistivity of metallic amorphous alloys, ρ 0, is typically in the range 50 µΩ cm < ρ 0 < 310 µΩ cm corresponding to a mean free path of conduction electrons of order a few interatomic distances. In crystalline metals with low defect levels such as Cu however, the residual electrical resistivity is about ρ 0 ≈ 1.54 × 10-2 µΩ cm, leading to extensive progression of free electrons through the crystalline material, of typically up to 4 × 106 nm. The relatively 'high' values for the electrical resistivity of distorted Sc75Fe25 alloys are discussed here within the framework of the wave character of electrons. The present investigation of amorphous and nanoglass Sc75Fe25 over the temperature range 1.9-320 K, focuses on clarification of the temperature dependence of the resistivity, ρ(T). These alloys systems, which show a range of behaviours for temperature dependent resistivity-including temperature independent residual resistivity, as well as positive and negative polarities for the slope dρ(T)/dT-are examined in detail.

Predator Preference for Bt-Fed Spodoptera frugiperda (Lepidoptera: Noctuidae) Prey: Implications for Insect Resistance Management in Bt Maize Seed Blends.

Understanding indirect, trophic-level effects of genetically engineered plants, expressing insecticidal proteins derived from the bacterium, Bacillus thuringiensis (Bt), is essential to the ecological risk assessment process. In this study, we examine potential indirect, trophic-level effects of Bt-sensitive prey using the predator, Harmonia axyridis (Pallas), feeding upon Spodoptera frugiperda (J.E. Smith) larvae, which had delayed development (lower body mass) following ingestion of Cry1Ab maize leaves. We found no adverse effects on development and survival when H. axyridis larvae were fed S. frugiperda larvae that had fed on Cry1Ab maize tissue. Presence of Cry1Ab in H. axyridis decreased considerably after switching to another diet within 48 h. In a no-choice assay, H. axyridis larvae consumed more Bt-fed S. frugiperda than non-Bt-fed larvae. Preference for S. frugiperda feeding on Bt maize was confirmed in subsequent choice assays with H. axyridis predation on Bt-fed, 1-5-d-old S. frugiperda larvae. We suggest that H. axyridis preferred prey, not based on whether it had fed on Bt or non-Bt maize, but rather on larval mass, and they compensated for the nutritional deficiency of lighter larvae through increased consumption. Pest larvae with variable levels of resistance developing on Bt diet are often stunted versus sensitive larvae developing on non-Bt diet. It is possible that such larvae may be preferentially removed from local field populations. These results may have implications for insect resistance management and may be played out under field conditions where seed blends of Bt and non-Bt hybrids are planted.

New insight into magneto-structural phase transitions in layered TbMn2Ge2-based compounds.

The Tb1-xYxMn2Ge2 series (x = 0, 0.1, 0.2) compounds are found to exhibit two magnetic phase transitions with decreasing temperature: from the paramagnetic state to the antiferromagnetic interlayer state at TNinter and from an antiferromagnetic interlayer structure to a collinear ferrimagnetic interlayer structure at TCinter. Compared with the slight change of TNinter (409 K, 410 K and 417 K for x = 0, 0.1 and 0.2 respectively), the replacement of Y for Tb leads to a significant decrease in TCinter from 97.5 K for x = 0 to 74.6 K for x = 0.2. The variation in TCinter can be ascribed to the combination of two effects: (1) chemical pressure and (2) magnetic dilution effect by Y substitution for Tb. Besides, a strong anisotropic magnet-volume effect has been detected around TCinter in all compounds with Δa/a = 0.125%, 0.124% and 0.130% for x = 0, 0.1 and 0.2, respectively while no obvious effect is detected along the c-axis. The maximum magnetic entropy change were found to be -ΔSmax = 9.1 J kg-1 K-1, 11.9 J kg-1 K-1 and 6.3 J kg-1 K-1 with a field change from 0 T to 5 T for x = 0, 0.1, 0.2 respectively.

Magnetic structure and spin reorientation of quaternary Dy2Fe2Si2C.

We have investigated the low temperature magnetic properties of Dy2Fe2Si2C by using magnetisation, specific heat, x-ray diffraction, neutron powder diffraction and 57Fe Mössbauer spectroscopy measurements over the temperature range 1.5 K-300 K. Dy2Fe2Si2C exhibits two magnetic transitions at low temperatures: an antiferromagnetic transition at [Formula: see text] K and a spin-reorientation transition at [Formula: see text] K. The magnetic structure above T t can be described with a propagation vector [Formula: see text] with the ordering of the Dy magnetic moments along the monoclinic b-axis whereas on cooling below T t the Dy moment tips away from the b-axis towards the ac-plane. We find that the spin-reorientation in Dy2Fe2Si2C is mainly driven by the competition between the second-order crystal field term B 20 and the higher-order terms, in particular B 40 and B 64.

Host-mediated shift in the cold tolerance of an invasive insect.

While many insects cannot survive the formation of ice within their bodies, a few species can. On the evolutionary continuum from freeze-intolerant (i.e., freeze-avoidant) to freeze-tolerant insects, intermediates likely exist that can withstand some ice formation, but not enough to be considered fully freeze tolerant. Theory suggests that freeze tolerance should be favored over freeze avoidance among individuals that have low relative fitness before exposure to cold. For phytophagous insects, numerous studies have shown that host (or nutrition) can affect fitness and cold-tolerance strategy, respectively, but no research has investigated whether changes in fitness caused by different hosts of polyphagous species could lead to systematic changes in cold-tolerance strategy. We tested this relationship with the invasive, polyphagous moth, Epiphyas postvittana (Walker). Host affected components of fitness, such as larval survivorship rates, pupal mass, and immature developmental times. Host species also caused a dramatic change in survival of late-instar larvae after the onset of freezing-from less than 8% to nearly 80%. The degree of survival after the onset of freezing was inversely correlated with components of fitness in the absence of cold exposure. Our research is the first empirical evidence of an evolutionary mechanism that may drive changes in cold-tolerance strategies. Additionally, characterizing the effects of host plants on insect cold tolerance will enhance forecasts of invasive species dynamics, especially under climate change.

Cold Tolerance of Halyomorpha halys (Hemiptera: Pentatomidae) Across Geographic and Temporal Scales.

The brown marmorated stink bug, Halyomorpha halys (Stål), is native to eastern Asia and is presently invading North America. Little is known about the exposure to and effects of winter temperatures in newly invaded regions on H. halys The overwintering habitats that this species utilizes vary greatly in their thermal buffering capacity. They naturally overwinter in aggregations beneath loose bark on trees and in cliff outcroppings, but will also commonly aggregate in buildings. Effects of cold temperatures such as mortality and freezing have yet to be quantified in the invading population. We report that H. halys is chill intolerant (i.e., dies before reaching its freezing point), and that the degree of cold tolerance of populations in North America differs by season, sex, and acclimation location. The mean winter supercooling point (± SEM) of individuals acclimated in Minnesota was -17.06 °C ± 0.13 and in Virginia was -13.90 °C ± 0.09. By using laboratory assays of lower lethal temperatures and ambient air temperature records, we accurately forecasted mortality for field experiments in Minnesota and Virginia. Temperature refugia provided by human-built structures are likely crucial for overwintering survival during atypically cold winters and possibly contribute to the northern geographic range expansion of this economically damaging insect in the temperate climates of North America.

Degree-Day Prediction Models for the Flight Phenology of Western Bean Cutworm (Lepidoptera: Noctuidae) Assessed with the Concordance Correlation Coefficient.

Western bean cutworm, Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), is a native, univoltine pest of corn and dry beans in North America. The current degree-day model for predicting a specified percentage of yearly moth flight involves heat unit accumulation above 10°C after 1 May. However, because the moth's observed range has expanded into the northern and eastern United States, there is concern that suitable temperatures before May could allow for significant S. albicosta development. Daily blacklight moth catch and temperature data from four Nebraska locations were used to construct degree-day models using simple or sine-wave methods, starting dates between 1 January and 1 May, and lower (-5 to 15°C) and upper (20 to 43.3°C) developmental thresholds. Predicted dates of flight from these models were compared with observed flight dates using independent datasets to assess model performance. Model performance was assessed with the concordance correlation coefficient to concurrently evaluate precision and accuracy. The best model for predicting timing of S. albicosta flight used simple degree-day calculations beginning on 1 March, a 3.3°C (38°F) lower threshold, and a 23.9°C (75°F) upper threshold. The revised cumulative flight model indicated field scouting to estimate moth egg density at the time of 25% flight should begin when 1,432 degree-days (2,577 degree-days °F) have accumulated. These results underscore the importance of assessing multiple parameters in phenological models and utilizing appropriate assessment methods, which in this case may allow for improved timing of field scouting for S. albicosta.

Cold Hardiness of Winter-Acclimated Drosophila suzukii (Diptera: Drosophilidae) Adults.

Drosophila suzukii Matsumura, often called spotted wing drosophila, is an exotic vinegar fly that is native to Southeast Asia and was first detected in the continental United States in 2008. Previous modeling studies have suggested that D. suzukii might not survive in portions of the northern United States or southern Canada due to the effects of cold. As a result, we measured two aspects of insect cold tolerance, the supercooling point and lower lethal temperature, for D. suzukii summer-morph pupae and adults and winter-morph adults. Supercooling points were compared to adults of Drosophila melanogaster Meigen. The lower lethal temperature of D. suzukii winter-morph adults was significantly colder than that for D. suzukii summer-morph adults, while supercooling points of D. suzukii winter-morph adults were actually warmer than that for D. suzukii summer-morph adults and pupae. D. suzukii summer-morph adult supercooling points were not significantly different than those for D. melanogaster adults. These measures indicate that D. suzukii is a chill intolerant insect, and winter-morph adults are the most cold-tolerant life stage. These results can be used to improve predictions of where D. suzukii might be able to establish overwintering populations and cause extensive damage to spring fruit crops.

Bt Maize Seed Mixtures for Helicoverpa zea (Lepidoptera: Noctuidae): Larval Movement, Development, and Survival on Non-transgenic Maize.

In 2012 and 2013, field trials were conducted near Rosemount, MN, to assess the movement and development of Helicoverpa zea (Boddie) larvae on non-Bt refuge corn plants within a seed mixture of non-Bt and Bt corn. The Bt corn hybrid expressed three Bt toxins-Cry1Ab, Cry1F, and Vip3A. As the use of seed mixtures for insect resistance management (IRM) continues to be implemented, it is necessary to further characterize how this IRM approach impacts resistance development in ear-feeding Lepidopteran pests. The potential for Bt pollen movement and cross pollination of the non-Bt ears in a seed mixture may lead to Bt toxin exposure to larvae developing on those refuge ears. Larval movement and development by H. zea, feeding on non-Bt refuge plants adjacent to either transgenic Bt or non-Bt plants, were measured to investigate the potential for unintended Bt exposure. Non-Bt plants were infested with H. zea eggs and subplots were destructively sampled twice per week within each treatment to assess larval development, location, and kernel injury. Results indicate that H. zea larval movement between plants is relatively low, ranging from 2-16% of larvae, and occurs mainly after reaching the second instar. Refuge plants in seed mixtures did not produce equivalent numbers of H. zea larvae, kernel injury, and larval development differed as compared with a pure stand of non-Bt plants. This suggests that there may be costs to larvae developing on refuge plants within seed mixtures and additional studies are warranted to define potential impacts.

Lack of depotentiation at basal ganglia output neurons in PD patients with levodopa-induced dyskinesia.

Parkinson's disease (PD), characterized by the loss of dopaminergic nigrostriatal projections, is a debilitating neurodegenerative disease which produces bradykinesia, rigidity, tremor and postural instability. The dopamine precursor levodopa (L-Dopa) is the most effective treatment for the amelioration of PD signs and symptoms, but long-term administration can lead to disabling motor fluctuations and L-Dopa-induced dyskinesias. In animal models of PD, a form of plasticity called depotentiation, or the reversal of previous potentiation, is selectively lost after the development of dyskinetic movements following L-Dopa treatment. We investigated whether low frequency stimulation (LFS) in the globus pallidus internus (GPi) and substantia nigra pars reticulata (SNr) could induce depotentiation at synapses that had already undergone high frequency stimulation (HFS)-induced potentiation. To do so, we measured the field potentials (fEPs) evoked by stimulation from a nearby microelectrode in 28 patients undergoing implantation of deep brain stimulating (DBS) electrodes in the subthalamic nucleus (STN) or GPi. We found that GPi and SNr synapses in patients with less severe dyskinesia underwent greater depotentiation following LFS than in patients with more severe dyskinesia. This demonstration of impaired depotentiation in basal ganglia output nuclei in PD patients with dyskinesia is an important validation of animal models of levodopa-induced dyskinesia. The ability of a synapse to reverse previous potentiation may be crucial to the normal function of the BG, perhaps by preventing saturation of the storage capacity required in motor learning and optimal motor function. Loss of this ability at the output nuclei may underlie, or contribute to the cellular basis of dyskinetic movements.