The projections from the amygdala and hippocampus (including subiculum and presubiculum) to prefrontal cortex were compared using anterograde tracers injected into macaque monkeys (Macaca ...fascicularis, Macaca mulatta). Almost all prefrontal areas were found to receive some amygdala inputs. These connections, which predominantly arose from the intermediate and magnocellular basal nucleus, were particularly dense in parts of the medial and orbital prefrontal cortex. Contralateral inputs were not, however, observed. The hippocampal projections to prefrontal areas were far more restricted, being confined to the ipsilateral medial and orbital prefrontal cortex (within areas 11, 13, 14, 24a, 32, and 25). These hippocampal projections principally arose from the subiculum, with the fornix providing the sole route. Thus, while the lateral prefrontal cortex essentially receives only amygdala inputs, the orbital prefrontal cortex receives both amygdala and hippocampal inputs, though these typically target different areas. Only in medial prefrontal cortex do direct inputs from both structures terminate in common sites. But, even when convergence occurs within an area, the projections predominantly terminate in different lamina (hippocampal inputs to layer III and amygdala inputs to layers I, II, and VI). The resulting segregation of prefrontal inputs could enable the parallel processing of different information types in prefrontal cortex.
Structural variation of the genome involves kilobase- to megabase-sized deletions, duplications, insertions, inversions, and complex combinations of rearrangements. We introduce high-throughput and ...massive paired-end mapping (PEM), a large-scale genome-sequencing method to identify structural variants (SVs) ~3 kilobases (kb) or larger that combines the rescue and capture of paired ends of 3-kb fragments, massive 454 sequencing, and a computational approach to map DNA reads onto a reference genome. PEM was used to map SVs in an African and in a putatively European individual and identified shared and divergent SVs relative to the reference genome. Overall, we fine-mapped more than 1000 SVs and documented that the number of SVs among humans is much larger than initially hypothesized; many of the SVs potentially affect gene function. The breakpoint junction sequences of more than 200 SVs were determined with a novel pooling strategy and computational analysis. Our analysis provided insights into the mechanisms of SV formation in humans.
Context. The colour fluctuations of type Ia supernovae (SNe Ia) include intrinsic and extrinsic components, which both contribute to the observed variability. Previous works proposed a statistical ...separation of these two contributions, but the individual intrinsic colour contributions of each SN Ia were not extracted. In addition, a large uncertainty remains on the value of the parameter RV, which characterises the dust extinction formula. Aims. Leveraging the known parameterisation of the extinction formula for dust in our Galaxy, and applying it to the host galaxy of SNe Ia, we propose a new method of separation –valid for each SN– using the correlations between colour fluctuations. This also allows us to derive a well-constrained value of the extinction parameter RV with different, possibly smaller systematic errors. We also define a three-dimensional space of intrinsic colour fluctuations. Methods. The key ingredients in this attempt at separating the intrinsic and extinction colour components for each SN –and subsequently measuring RV– are the assumption of a linearized dependence of magnitude on the extinction component of colour, a one-dimensional extra-intrinsic colour space (in addition to Ca II H&Kλ3945 and Si IIλ4131 contributions) over four independent colours, and the absence of correlation between the intrinsic and extrinsic variabilities. Results. We show that a consistent solution is found under the previous assumptions, but the observed systematic trends point to a (small) inadequacy of the extinction formula. Once corrected, all systematic extinction effects can be cancelled by choosing a single scaling of the extinction colour component as well as an appropriate value of RV = 2.181 ± 0.117. The observed colours are described within an accuracy of 0.025 mag. The resulting magnitude variability is 0.13 over all UBVRI bandpasses, and this fluctuation is shown to be independent of the bandpass to within 0.02 mag.
Although forest edges have been studied extensively as an important consequence of fragmentation, a unifying theory of edge influence has yet to be developed. Our objective was to take steps toward ...the development of such a theory by (1) synthesizing the current knowledge of patterns of forest structure and composition at anthropogenically created forest edges, (2) developing hypotheses about the magnitude and distance of edge influence that consider the ecological processes influencing these patterns, and (3) identifying needs for future research. We compiled data from 44 published studies on edge influence on forest structure and composition in boreal, temperate, and tropical forests. Abiotic and biotic gradients near created forest edges generate a set of primary responses to edge creation. Indirect effects from these primary responses and the original edge gradient perpetuate edge influence, leading to secondary responses. Further changes in vegetation affect the edge environment, resulting in ongoing edge dynamics. We suggest that the magnitude and distance of edge influence are a direct function of the contrast in structure and composition between adjacent communities on either side of the edge. Local factors such as climate, edge characteristics, stand attributes, and biotic factors affect patch contrast. Regional factors define the context within which to assess the ecological significance of edge influence (the degree to which the edge habitat differs from interior forest habitat). Our hypotheses will help predict edge influence on structure and composition in forested ecosystems, an important consideration for conservation. For future research on forest edges in fragmented landscapes, we encourage the testing of our hypotheses, the use of standardized methodology, complete descriptions of study sites, studies on other types of edges, synthesis of edge influence on different components of the ecosystem, and investigations of edges in a landscape context.
Although neurotechnology careers are on the rise, and neuroscience curriculums have significantly grown at the undergraduate and graduate levels, increasing neuroscience and neurotechnology exposure ...in high school curricula has been an ongoing challenge. This is due, in part, to difficulties in converting cutting-edge neuroscience research into hands-on activities that are accessible for high school students and affordable for high school educators. Here, we describe and characterize a low-cost, easy-to-construct device to enable students to record rapid Drosophila melanogaster (fruit fly) behaviors during optogenetics experiments. The device is generated from inexpensive Arduino kits and utilizes a smartphone for video capture, making it easy to adopt in a standard biology laboratory. We validate this device is capable of replicating optogenetics experiments performed with more sophisticated setups at leading universities and institutes. We incorporate the device into a high school neuroengineering summer workshop. We find student participation in the workshop significantly enhances their understanding of key neuroscience and neurotechnology concepts, demonstrating how this device can be utilized in high school settings and undergraduate research laboratories seeking low-cost alternatives.
Leishmania parasites alternate between extracellular promastigote stages in the insect vector and an obligate intracellular amastigote stage that proliferates within the phagolysosomal compartment of ...macrophages in the mammalian host. Most enzymes involved in Leishmania central carbon metabolism are constitutively expressed and stage-specific changes in energy metabolism remain poorly defined. Using (13)C-stable isotope resolved metabolomics and (2)H2O labelling, we show that amastigote differentiation is associated with reduction in growth rate and induction of a distinct stringent metabolic state. This state is characterized by a global decrease in the uptake and utilization of glucose and amino acids, a reduced secretion of organic acids and increased fatty acid β-oxidation. Isotopomer analysis showed that catabolism of hexose and fatty acids provide C4 dicarboxylic acids (succinate/malate) and acetyl-CoA for the synthesis of glutamate via a compartmentalized mitochondrial tricarboxylic acid (TCA) cycle. In vitro cultivated and intracellular amastigotes are acutely sensitive to inhibitors of mitochondrial aconitase and glutamine synthetase, indicating that these anabolic pathways are essential for intracellular growth and virulence. Lesion-derived amastigotes exhibit a similar metabolism to in vitro differentiated amastigotes, indicating that this stringent response is coupled to differentiation signals rather than exogenous nutrient levels. Induction of a stringent metabolic response may facilitate amastigote survival in a nutrient-poor intracellular niche and underlie the increased dependence of this stage on hexose and mitochondrial metabolism.
Information on the growth rate and metabolism of microbial pathogens that cause long-term chronic infections is limited, reflecting the absence of suitable tools for measuring these parameters in ...vivo. Here, we have measured the replication and physiological state of Leishmania mexicana parasites in murine inflammatory lesions using 2H2O labeling. Infected BALB/c mice were labeled with 2H2O for up to 4 months, and the turnover of parasite DNA, RNA, protein and membrane lipids estimated from the rate of deuterium enrichment in constituent pentose sugars, amino acids, and fatty acids, respectively. We show that the replication rate of parasite stages in these tissues is very slow (doubling time of ~12 days), but remarkably constant throughout lesion development. Lesion parasites also exhibit markedly lower rates of RNA synthesis, protein turnover and membrane lipid synthesis than parasite stages isolated from ex vivo infected macrophages or cultured in vitro, suggesting that formation of lesions induces parasites to enter a semi-quiescent physiological state. Significantly, the determined parasite growth rate accounts for the overall increase in parasite burden indicating that parasite death and turnover of infected host cells in these lesions is minimal. We propose that the Leishmania response to lesion formation is an important adaptive strategy that minimizes macrophage activation, providing a permissive environment that supports progressive expansion of parasite burden. This labeling approach can be used to measure the dynamics of other host-microbe interactions in situ.
As part of an on-going effort to identify, understand and correct for astrophysics biases in the standardization of Type Ia supernovae (SN Ia) for cosmology, we have statistically classified a large ...sample of nearby SNe Ia into those that are located in predominantly younger or older environments. This classification is based on the specific star formation rate measured within a projected distance of 1 kpc from each SN location (LsSFR). This is an important refinement compared to using the local star formation rate directly, as it provides a normalization for relative numbers of available SN progenitors and is more robust against extinction by dust. We find that the SNe Ia in predominantly younger environments are Δ
Y
= 0.163 ± 0.029 mag (5.7
σ
) fainter than those in predominantly older environments after conventional light-curve standardization. This is the strongest standardized SN Ia brightness systematic connected to the host-galaxy environment measured to date. The well-established step in standardized brightnesses between SNe Ia in hosts with lower or higher total stellar masses is smaller, at Δ
M
= 0.119 ± 0.032 mag (4.5
σ
), for the same set of SNe Ia. When fit simultaneously, the environment-age offset remains very significant, with Δ
Y
= 0.129 ± 0.032 mag (4.0
σ
), while the global stellar mass step is reduced to Δ
M
= 0.064 ± 0.029 mag (2.2
σ
). Thus, approximately 70% of the variance from the stellar mass step is due to an underlying dependence on environment-based progenitor age. Also, we verify that using the local star formation rate alone is not as powerful as LsSFR at sorting SNe Ia into brighter and fainter subsets. Standardization that only uses the SNe Ia in younger environments reduces the total dispersion from 0.142 ± 0.008 mag to 0.120 ± 0.010 mag. We show that as environment-ages evolve with redshift, a strong bias, especially on the measurement of the derivative of the dark energy equation of state, can develop. Fortunately, data that measure and correct for this effect using our local specific star formation rate indicator, are likely to be available for many next-generation SN Ia cosmology experiments.
The frontopolar cortex (FPC) is, to date, one of the least understood regions of the prefrontal cortex. The current understanding of its function suggests that it plays a role in the control of ...exploratory behaviors by coordinating the activities of other prefrontal cortex areas involved in decision-making and exploiting actions based on their outcomes. Based on this hypothesis, FPC would drive fast-learning processes through a valuation of the different alternatives. In our study, we used a modified version of a well-known paradigm, the object-in-place (OIP) task, to test this hypothesis in electrophysiology. This paradigm is designed to maximize learning, enabling monkeys to learn in one trial, which is an ability specifically impaired after a lesion of the FPC. We showed that FPC neurons presented an extremely specific pattern of activity by representing the learning stage, exploration versus exploitation, and the goal of the action. However, our results do not support the hypothesis that neurons in the frontal pole compute an evaluation of different alternatives. Indeed, the position of the chosen target was strongly encoded at its acquisition, but the position of the unchosen target was not. Once learned, this representation was also found at the problem presentation, suggesting a monitoring activity of the synthetic goal preceding its acquisition. Our results highlight important features of FPC neurons in fast-learning processes without confirming their role in the disengagement of cognitive control from the current goals.
In the absence of sensory stimuli, spontaneous activity in the brain has been shown to exhibit organization at multiple spatiotemporal scales. In the macaque auditory cortex, responses to acoustic ...stimuli are tonotopically organized within multiple, adjacent frequency maps aligned in a caudorostral direction on the supratemporal plane (STP) of the lateral sulcus. Here, we used chronic microelectrocorticography to investigate the correspondence between sensory maps and spontaneous neural fluctuations in the auditory cortex. We first mapped tonotopic organization across 96 electrodes spanning approximately two centimeters along the primary and higher auditory cortex. In separate sessions, we then observed that spontaneous activity at the same sites exhibited spatial covariation that reflected the tonotopic map of the STP. This observation demonstrates a close relationship between functional organization and spontaneous neural activity in the sensory cortex of the awake monkey.
► Simultaneous large-scale field potential recording from intrasulcal cortical areas ► Mirror symmetric tonotopic maps identified with high gamma power ► The structure of the tonotopic maps emerged spontaneously in awake resting state
Fukushima et al. use intrasulcal electrocorticography to examine population neural activity in the auditory cortex. They delineate the sensory map and its close relationship to the spontaneous activity in the awake, resting state.
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