Dynamic gating in the nucleus accumbens: Behavioral state-dependent synchrony with the prefrontal cortex and hippocampus

Contextual and sensory information, goals, and the motor plan to achieve them are integrated in the nucleus accumbens (NA). Although this integration needs flexibility to operate in a variety of environments, models of NA function rarely consider changing behavioral states. Here, intracellular recordings in anesthetized rats revealed rapid changes in the synchronization between NA up states and prefrontal cortical (PFC) local field potentials (LFPs). The synchronization of the NA with the PFC and ventral hippocampus also varied over time in awake rats, depending on the behavioral state of the animal: NA LFPs followed hippocampal theta rhythms during spatial exploration, but not during an operant task when they were instead synchronized with slower PFC rhythms. These data indicate that the ability of the NA to follow cortical inputs can rapidly change, allowing for a mechanism that could select an optimal response for a given behavioral condition

Computational Properties of the Hippocampus Increase the Efficiency of Goal-Directed Foraging through Hierarchical Reinforcement Learning

Sherpa Romeo green journal; open accessThe mammalian brain is thought to use a version of Model-based Reinforcement Learning (MBRL) to guide “goal-directed” behavior, wherein animals consider goals and make plans to acquire desired outcomes. However, conventional MBRL algorithms do not fully explain animals’ ability to rapidly adapt to environmental changes, or learn multiple complex tasks. They also require extensive computation, suggesting that goal-directed behavior is cognitively expensive. We propose here that key features of processing in the hippocampus support a flexible MBRL mechanism for spatial navigation that is computationally efficient and can adapt quickly to change. We investigate this idea by implementing a computational MBRL framework that incorporates features inspired by computational properties of the hippocampus: a hierarchical representation of space, “forward sweeps” through future spatial trajectories, and context-driven remapping of place cells. We find that a hierarchical abstraction of space greatly reduces the computational load (mental effort) required for adaptation to changing environmental conditions, and allows efficient scaling to large problems. It also allows abstract knowledge gained at high levels to guide adaptation to new obstacles. Moreover, a context-driven remapping mechanism allows learning and memory of multiple tasks. Simulating dorsal or ventral hippocampal lesions in our computational framework qualitatively reproduces behavioral deficits observed in rodents with analogous lesions. The framework may thus embody key features of how the brain organizes model-based RL to efficiently solve navigation and other difficult tasks.Ye

Context, emotion, and the strategic pursuit of goals: interactions among multiple brain systems controlling motivated behavior

Sherpa Rome green journal . Open access, published under the CC-BY license.Motivated behavior exhibits properties that change with experience and partially dissociate among a number of brain structures. Here, we review evidence from rodent experiments demonstrating that multiple brain systems acquire information in parallel and either cooperate or compete for behavioral control. We propose a conceptual model of systems interaction wherein a ventral emotional memory network involving ventral striatum (VS), amygdala, ventral hippocampus, and ventromedial prefrontal cortex triages behavioral responding to stimuli according to their associated affective outcomes. This system engages autonomic and postural responding (avoiding, ignoring, approaching) in accordance with associated stimulus valence (negative, neutral, positive), but does not engage particular operant responses. Rather, this emotional system suppresses or invigorates actions that are selected through competition between goal-directed control involving dorsomedial striatum (DMS) and habitual control involving dorsolateral striatum (DLS). The hippocampus provides contextual specificityto the emotional system, and provides an information rich input to the goal-directed system for navigation and discriminations involving ambiguous contexts, complex sensory configurations, or temporal ordering. The rapid acquisition and high capacity for episodic associations in the emotional system may unburden the more complex goal-directed system and reduce interference in the habit system from processing contingencies of neutral stimuli. Interactions among these systems likely involve inhibitory mechanisms and neuromodulation in the striatum to form a dominant response strategy. Innate traits, training methods, and task demands contribute to the nature of these interactions, which can include incidental learning in non-dominant systems. Addition of these features to reinforcement learning models of decision-makingmay better aligntheoretical predictions with behavioral and neural correlates in animals.Ye

Single photon source characterization with a superconducting single photon detector

Superconducting single photon detectors (SSPD) based on nanopatterned niobium nitride wires offer single photon counting at fast rates, low jitter, and low dark counts, from visible wavelengths well into the infrared. We demonstrate the first use of an SSPD, packaged in a commercial cryocooler, for single photon source characterization. The source is an optically pumped, microcavity-coupled InGaAs quantum dot, emitting single photons on demand at 902 nm. The SSPD replaces the second silicon Avalanche Photodiode (APD) in a Hanbury-Brown Twiss interferometer measurement of the source second-order correlation function, g (2) (tau). The detection efficiency of the superconducting detector system is >2 % (coupling losses included). The SSPD system electronics jitter is 170 ps, versus 550 ps for the APD unit, allowing the source spontaneous emission lifetime to be measured with improved resolution.Comment: 8 page

The Nucleus Accumbens: A Switchboard for Goal-Directed Behaviors

Reward intake optimization requires a balance between exploiting known sources of rewards and exploring for new sources. The prefrontal cortex (PFC) and associated basal ganglia circuits are likely candidates as neural structures responsible for such balance, while the hippocampus may be responsible for spatial/contextual information. Although studies have assessed interactions between hippocampus and PFC, and between hippocampus and the nucleus accumbens (NA), it is not known whether 3-way interactions among these structures vary under different behavioral conditions. Here, we investigated these interactions with multichannel recordings while rats explored an operant chamber and while they performed a learned lever-pressing task for reward in the same chamber shortly afterward. Neural firing and local field potentials in the NA core synchronized with hippocampal activity during spatial exploration, but during lever pressing they instead synchronized more strongly with the PFC. The latter is likely due to transient drive of NA neurons by bursting prefrontal activation, as in vivo intracellular recordings in anesthetized rats revealed that NA up states can transiently synchronize with spontaneous PFC activity and PFC stimulation with a bursting pattern reliably evoked up states in NA neurons. Thus, the ability to switch synchronization in a task-dependent manner indicates that the NA core can dynamically select its inputs to suit environmental demands, thereby contributing to decision-making, a function that was thought to primarily depend on the PFC

XSTREAM: A practical algorithm for identification and architecture modeling of tandem repeats in protein sequences

<p>Abstract</p> <p>Background</p> <p>Biological sequence repeats arranged in tandem patterns are widespread in DNA and proteins. While many software tools have been designed to detect DNA tandem repeats (TRs), useful algorithms for identifying protein TRs with varied levels of degeneracy are still needed.</p> <p>Results</p> <p>To address limitations of current repeat identification methods, and to provide an efficient and flexible algorithm for the detection and analysis of TRs in protein sequences, we designed and implemented a new computational method called XSTREAM. Running time tests confirm the practicality of XSTREAM for analyses of multi-genome datasets. Each of the key capabilities of XSTREAM (e.g., merging, nesting, long-period detection, and TR architecture modeling) are demonstrated using anecdotal examples, and the utility of XSTREAM for identifying TR proteins was validated using data from a recently published paper.</p> <p>Conclusion</p> <p>We show that XSTREAM is a practical and valuable tool for TR detection in protein and nucleotide sequences at the multi-genome scale, and an effective tool for modeling TR domains with diverse architectures and varied levels of degeneracy. Because of these useful features, XSTREAM has significant potential for the discovery of naturally-evolved modular proteins with applications for engineering novel biostructural and biomimetic materials, and identifying new vaccine and diagnostic targets.</p

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

The unruptured intracranial aneurysm treatment score A multidisciplinary consensus

Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (v(r)*) (v(r)* 5 0 indicating excellent agreement and v(r)* = 1 indicating poor agreement). Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (v(r)*) for both cohorts was 0.026 (95% CI 0.019-0.033). Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.Peer reviewe

Stimulation of osteogenic differentiation in human osteoprogenitor cells by pulsed electromagnetic fields: an in vitro study

Background: Although pulsed electromagnetic field (PEMF) stimulation may be clinically beneficial during fracture healing and for a wide range of bone disorders, there is still debate on its working mechanism. Mesenchymal stem cells are likely mediators facilitating the observed clinical effects of PEMF. Here, we performed in vitro experiments to investigate the effect of PEMF stimulation on human bone marrow-derived stromal cell (BMSC) metabolism and, specifically, whether PEMF can stimulate their osteogenic differentiation. Methods: BMSCs derived from four different donors were cultured in osteogenic medium, with the PEMF treated group being continuously exposed to a 15 Hz, 1 Gauss EM field, consisting of 5-millisecond bursts with 5-microsecond pulses. On culture day 1, 5, 9, and 14, cells were collected for biochemical analysis (DNA amount, alkaline phosphatase activity, calcium deposition), expression of various osteoblast-relevant genes and activation of extracellular signal-regulated kinase (ERK) signaling. Differences between treated and control groups were analyzed using the Wilcoxon signed rank test, and considered significant when p < 0.05. Results: Biochemical analysis revealed significant, differentiation stage-dependent, PEMF-induced differences: PEMF increased mineralization at day 9 and 14, without altering alkaline phosphatase activity. Cell proliferation, as measured by DNA amounts, was not affected by PEMF until day 14. Here, DNA content stagnated in PEMF treated group, resulting in less DNA compared to control. Quantitative RT-PCR revealed that during early culture, up to day 9, PEMF treatment increased mRNA levels of bone morphogenetic protein 2, transforming growth factor-beta 1, osteoprotegerin, matrix metalloproteinase-1 and-3, osteocalcin, and bone sialoprotein. In contrast, receptor activator of NF-B ligand expression was primarily stimulated on day 14. ERK1/2 phosphorylation was not affected by PEMF stimulation. Conclusions: PEMF exposure of differentiating human BMSCs enhanced mineralization and seemed to induce differentiation at the expense of proliferation. The osteogenic stimulus of PEMF was confirmed by the up-regulation of several osteogenic marker genes in the PEMF treated group, which preceded the deposition of mineral itself. These findings indicate that PEMF can directly stimulate osteoprogenitor cells towards osteogenic differentiation. This supports the theory that PEMF treatment may recruit these cells to facilitate an osteogenic response in vivo. © 2010 Jansen et al; licensee BioMed Central Ltd