Reactivating Memories for Consolidation

The consolidation of memory is thought to occur via a hippocampal-neocortical dialog involving reactivation of memory patterns in the hippocampus during sharp-wave ripples. In this issue of Neuron, Nakashiba et al. demonstrate that CA3 output is required for consolidation of contextual fear memory. They also show that lack of CA3 output results in a decrease in ripple-related reactivation, providing additional evidence for a role of ripple-related reactivation in the consolidation process

Transient Slow Gamma Synchrony Underlies Hippocampal Memory Replay

SummaryThe replay of previously stored memories during hippocampal sharp wave ripples (SWRs) is thought to support both memory retrieval and consolidation in distributed hippocampal-neocortical circuits. Replay events consist of precisely timed sequences of spikes from CA3 and CA1 neurons that are coordinated both within and across hemispheres. The mechanism of this coordination is not understood. Here, we show that during SWRs in both awake and quiescent states there are transient increases in slow gamma (20-50 Hz) power and synchrony across dorsal CA3 and CA1 networks of both hemispheres. These gamma oscillations entrain CA3 and CA1 spiking. Moreover, during awake SWRs, higher levels of slow gamma synchrony are predictive of higher quality replay of past experiences. Our results indicate that CA3-CA1 gamma synchronization is a central component of awake memory replay and suggest that transient gamma synchronization serves as a clocking mechanism to enable coordinated memory reactivation across the hippocampal network

Environment sensing and response mediated by ABC transporters

<p>Abstract</p> <p>Background</p> <p>Transporter proteins are one of an organism’s primary interfaces with the environment. The expressed set of transporters mediates cellular metabolic capabilities and influences signal transduction pathways and regulatory networks. The functional annotation of most transporters is currently limited to general classification into families. The development of capabilities to map ligands with specific transporters would improve our knowledge of the function of these proteins, improve the annotation of related genomes, and facilitate predictions for their role in cellular responses to environmental changes.</p> <p>Results</p> <p>To improve the utility of the functional annotation for ABC transporters, we expressed and purified the set of solute binding proteins from <it>Rhodopseudomonas palustris</it> and characterized their ligand-binding specificity. Our approach utilized ligand libraries consisting of environmental and cellular metabolic compounds, and fluorescence thermal shift based high throughput ligand binding screens. This process resulted in the identification of specific binding ligands for approximately 64% of the purified and screened proteins. The collection of binding ligands is representative of common functionalities associated with many bacterial organisms as well as specific capabilities linked to the ecological niche occupied by <it>R. palustris</it>.</p> <p>Conclusion</p> <p>The functional screen identified specific ligands that bound to ABC transporter periplasmic binding subunits from <it>R. palustris</it>. These assignments provide unique insight for the metabolic capabilities of this organism and are consistent with the ecological niche of strain isolation. This functional insight can be used to improve the annotation of related organisms and provides a route to evaluate the evolution of this important and diverse group of transporter proteins.</p

Comparison of the diagnostic accuracy of three current guidelines for the evaluation of asymptomatic pancreatic cystic neoplasms.

Asymptomatic pancreatic cysts are a common clinical problem but only a minority of these cases progress to cancer. Our aim was to compare the accuracy to detect malignancy of the 2015 American Gastroenterological Association (AGA), the 2012 International Consensus/Fukuoka (Fukuoka guidelines [FG]), and the 2010 American College of Radiology (ACR) guidelines.We conducted a retrospective study at 3 referral centers for all patients who underwent resection for an asymptomatic pancreatic cyst between January 2008 and December 2013. We compared the accuracy of 3 guidelines in predicting high-grade dysplasia (HGD) or cancer in resected cysts. We performed logistic regression analyses to examine the association between cyst features and risk of HGD or cancer.A total of 269 patients met inclusion criteria. A total of 228 (84.8%) had a benign diagnosis or low-grade dysplasia on surgical pathology, and 41 patients (15.2%) had either HGD (n = 14) or invasive cancer (n = 27). Of the 41 patients with HGD or cancer on resection, only 3 patients would have met the AGA guideline\u27s indications for resection based on the preoperative cyst characteristics, whereas 30/41 patients would have met the FG criteria for resection and 22/41 patients met the ACR criteria. The sensitivity, specificity, positive predictive value, negative predictive value of HGD, and/or cancer of the AGA guidelines were 7.3%, 88.2%, 10%, and 84.1%, compared to 73.2%, 45.6%, 19.5%, and 90.4% for the FG and 53.7%, 61%, 19.8%, and 88% for the ACR guidelines. In multivariable analysis, cyst size \u3e3 cm, compared to ≤3 cm, (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.11, 4.2) and each year increase in age (OR = 1.07, 95% CI = 1.03, 1.11) were positively associated with risk of HGD or cancer on resection.In patients with asymptomatic branch duct-intraductal papillary mucinous neoplasms or mucinous cystic neoplasms who underwent resection, the prevalence rate of HGD or cancer was 15.2%. Using the 2015 AGA criteria for resection would have missed 92.6% of patients with HGD or cancer. The more inclusive FG and ACR had a higher sensitivity for HGD or cancer but lower specificity. Given the current deficiencies of these guidelines, it will be important to determine the acceptable rate of false-positives in order to prevent a single true-positive

BRAIN Initiative: Cutting-Edge Tools and Resources for the Community.

The overarching goal of the NIH BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative is to advance the understanding of healthy and diseased brain circuit function through technological innovation. Core principles for this goal include the validation and dissemination of the myriad innovative technologies, tools, methods, and resources emerging from BRAIN-funded research. Innovators, BRAIN funding agencies, and non-Federal partners are working together to develop strategies for making these products usable, available, and accessible to the scientific community. Here, we describe several early strategies for supporting the dissemination of BRAIN technologies. We aim to invigorate a dialogue with the neuroscience research and funding community, interdisciplinary collaborators, and trainees about the existing and future opportunities for cultivating groundbreaking research products into mature, integrated, and adaptable research systems. Along with the accompanying Society for Neuroscience 2019 Mini-Symposium, "BRAIN Initiative: Cutting-Edge Tools and Resources for the Community," we spotlight the work of several BRAIN investigator teams who are making progress toward providing tools, technologies, and services for the neuroscience community. These tools access neural circuits at multiple levels of analysis, from subcellular composition to brain-wide network connectivity, including the following: integrated systems for EM- and florescence-based connectomics, advances in immunolabeling capabilities, and resources for recording and analyzing functional connectivity. Investigators describe how the resources they provide to the community will contribute to achieving the goals of the NIH BRAIN Initiative. Finally, in addition to celebrating the contributions of these BRAIN-funded investigators, the Mini-Symposium will illustrate the broader diversity of BRAIN Initiative investments in cutting-edge technologies and resources

Genome of the epsilonproteobacterial chemolithoautotroph Sulfurimonas denitrificans

Author Posting. © American Society for Microbiology, 2008. This article is posted here by permission of American Society for Microbiology for personal use, not for redistribution. The definitive version was published in Applied and Environmental Microbiology 74 (2008): 1145-1156, doi:10.1128/AEM.01844-07.Sulfur-oxidizing epsilonproteobacteria are common in a variety of sulfidogenic environments. These autotrophic and mixotrophic sulfur-oxidizing bacteria are believed to contribute substantially to the oxidative portion of the global sulfur cycle. In order to better understand the ecology and roles of sulfur-oxidizing epsilonproteobacteria, in particular those of the widespread genus Sulfurimonas, in biogeochemical cycles, the genome of Sulfurimonas denitrificans DSM1251 was sequenced. This genome has many features, including a larger size (2.2 Mbp), that suggest a greater degree of metabolic versatility or responsiveness to the environment than seen for most of the other sequenced epsilonproteobacteria. A branched electron transport chain is apparent, with genes encoding complexes for the oxidation of hydrogen, reduced sulfur compounds, and formate and the reduction of nitrate and oxygen. Genes are present for a complete, autotrophic reductive citric acid cycle. Many genes are present that could facilitate growth in the spatially and temporally heterogeneous sediment habitat from where Sulfurimonas denitrificans was originally isolated. Many resistance-nodulation-development family transporter genes (10 total) are present; of these, several are predicted to encode heavy metal efflux transporters. An elaborate arsenal of sensory and regulatory protein-encoding genes is in place, as are genes necessary to prevent and respond to oxidative stress.This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory, University of California, under contract W-7405-ENG-48. Genome closure was funded in part by a USF Innovative Teaching Grant (K.M.S.). S.M.S. received partial support through a fellowship from the Hanse Wissenschaftskolleg in Delmenhorst, Germany (http://www.h-w-k.de), and NSF grant OCE-0452333. K.M.S. is grateful for support from NSF grant MCB-0643713. M.H. was supported by a WHOI postdoctoral scholarship. M.G.K. was supported in part by incentive funds provided by the UofL-EVPR office, the KY Science and Engineering Foundation (KSEF-787-RDE-007), and the National Science Foundation (EF-0412129)

Complete genome sequence of the filamentous anoxygenic phototrophic bacterium Chloroflexus aurantiacus

<p>Abstract</p> <p>Background</p> <p><it>Chloroflexus aurantiacus </it>is a thermophilic filamentous anoxygenic phototrophic (FAP) bacterium, and can grow phototrophically under anaerobic conditions or chemotrophically under aerobic and dark conditions. According to 16S rRNA analysis, <it>Chloroflexi </it>species are the earliest branching bacteria capable of photosynthesis, and <it>Cfl. aurantiacus </it>has been long regarded as a key organism to resolve the obscurity of the origin and early evolution of photosynthesis. <it>Cfl. aurantiacus </it>contains a chimeric photosystem that comprises some characters of green sulfur bacteria and purple photosynthetic bacteria, and also has some unique electron transport proteins compared to other photosynthetic bacteria.</p> <p>Methods</p> <p>The complete genomic sequence of <it>Cfl. aurantiacus </it>has been determined, analyzed and compared to the genomes of other photosynthetic bacteria.</p> <p>Results</p> <p>Abundant genomic evidence suggests that there have been numerous gene adaptations/replacements in <it>Cfl. aurantiacus </it>to facilitate life under both anaerobic and aerobic conditions, including duplicate genes and gene clusters for the alternative complex III (ACIII), auracyanin and NADH:quinone oxidoreductase; and several aerobic/anaerobic enzyme pairs in central carbon metabolism and tetrapyrroles and nucleic acids biosynthesis. Overall, genomic information is consistent with a high tolerance for oxygen that has been reported in the growth of <it>Cfl. aurantiacus</it>. Genes for the chimeric photosystem, photosynthetic electron transport chain, the 3-hydroxypropionate autotrophic carbon fixation cycle, CO₂-anaplerotic pathways, glyoxylate cycle, and sulfur reduction pathway are present. The central carbon metabolism and sulfur assimilation pathways in <it>Cfl. aurantiacus </it>are discussed. Some features of the <it>Cfl. aurantiacus </it>genome are compared with those of the <it>Roseiflexus castenholzii </it>genome. <it>Roseiflexus castenholzii </it>is a recently characterized FAP bacterium and phylogenetically closely related to <it>Cfl. aurantiacus</it>. According to previous reports and the genomic information, perspectives of <it>Cfl. aurantiacus </it>in the evolution of photosynthesis are also discussed.</p> <p>Conclusions</p> <p>The genomic analyses presented in this report, along with previous physiological, ecological and biochemical studies, indicate that the anoxygenic phototroph <it>Cfl. aurantiacus </it>has many interesting and certain unique features in its metabolic pathways. The complete genome may also shed light on possible evolutionary connections of photosynthesis.</p

Rats use memory confidence to guide decisions.

Memory enables access to past experiences to guide future behavior. Humans can determine which memories to trust (high confidence) and which to doubt (low confidence). How memory retrieval, memory confidence, and memory-guided decisions are related, however, is not understood. In particular, how confidence in memories is used in decision making is unknown. We developed a spatial memory task in which rats were incentivized to gamble their time: betting more following a correct choice yielded greater reward. Rat behavior reflected memory confidence, with higher temporal bets following correct choices. We applied machine learning to identify a memory decision variable and built a generative model of memories evolving over time that accurately predicted both choices and confidence reports. Our results reveal in rats an ability thought to exist exclusively in primates and introduce a unified model of memory dynamics, retrieval, choice, and confidence