Heterogeneity in Kv2 Channel Expression Shapes Action Potential Characteristics and Firing Patterns in CA1 versus CA2 Hippocampal Pyramidal Neurons.

The CA1 region of the hippocampus plays a critical role in spatial and contextual memory, and has well-established circuitry, function and plasticity. In contrast, the properties of the flanking CA2 pyramidal neurons (PNs), important for social memory, and lacking CA1-like plasticity, remain relatively understudied. In particular, little is known regarding the expression of voltage-gated K+ (Kv) channels and the contribution of these channels to the distinct properties of intrinsic excitability, action potential (AP) waveform, firing patterns and neurotransmission between CA1 and CA2 PNs. In the present study, we used multiplex fluorescence immunolabeling of mouse brain sections, and whole-cell recordings in acute mouse brain slices, to define the role of heterogeneous expression of Kv2 family Kv channels in CA1 versus CA2 pyramidal cell excitability. Our results show that the somatodendritic delayed rectifier Kv channel subunits Kv2.1, Kv2.2, and their auxiliary subunit AMIGO-1 have region-specific differences in expression in PNs, with the highest expression levels in CA1, a sharp decrease at the CA1-CA2 boundary, and significantly reduced levels in CA2 neurons. PNs in CA1 exhibit a robust contribution of Guangxitoxin-1E-sensitive Kv2-based delayed rectifier current to AP shape and after-hyperpolarization potential (AHP) relative to that seen in CA2 PNs. Our results indicate that robust Kv2 channel expression confers a distinct pattern of intrinsic excitability to CA1 PNs, potentially contributing to their different roles in hippocampal network function

A toolbox of nanobodies developed and validated for use as intrabodies and nanoscale immunolabels in mammalian brain neurons.

Nanobodies (nAbs) are small, minimal antibodies that have distinct attributes that make them uniquely suited for certain biomedical research, diagnostic and therapeutic applications. Prominent uses include as intracellular antibodies or intrabodies to bind and deliver cargo to specific proteins and/or subcellular sites within cells, and as nanoscale immunolabels for enhanced tissue penetration and improved spatial imaging resolution. Here, we report the generation and validation of nAbs against a set of proteins prominently expressed at specific subcellular sites in mammalian brain neurons. We describe a novel hierarchical validation pipeline to systematically evaluate nAbs isolated by phage display for effective and specific use as intrabodies and immunolabels in mammalian cells including brain neurons. These nAbs form part of a robust toolbox for targeting proteins with distinct and highly spatially-restricted subcellular localization in mammalian brain neurons, allowing for visualization and/or modulation of structure and function at those sites

A Generalized Epidemic Process and Tricritical Dynamic Percolation

The renowned general epidemic process describes the stochastic evolution of a population of individuals which are either susceptible, infected or dead. A second order phase transition belonging to the universality class of dynamic isotropic percolation lies between endemic or pandemic behavior of the process. We generalize the general epidemic process by introducing a fourth kind of individuals, viz. individuals which are weakened by the process but not yet infected. This sensibilization gives rise to a mechanism that introduces a global instability in the spreading of the process and therefore opens the possibility of a discontinuous transition in addition to the usual continuous percolation transition. The tricritical point separating the lines of first and second order transitions constitutes a new universality class, namely the universality class of tricritical dynamic isotropic percolation. Using renormalized field theory we work out a detailed scaling description of this universality class. We calculate the scaling exponents in an $\epsilon$-expansion below the upper critical dimension $d_{c}=5$ for various observables describing tricritical percolation clusters and their spreading properties. In a remarkable contrast to the usual percolation transition, the exponents $\beta$ and ${\beta}^{\prime}$ governing the two order parameters, viz. the mean density and the percolation probability, turn out to be different at the tricritical point. In addition to the scaling exponents we calculate for all our static and dynamic observables logarithmic corrections to the mean-field scaling behavior at $d_c=5$.Comment: 21 pages, 10 figures, version to appear in Phys. Rev.

Formation and Evolution of Planetary Systems: Cold Outer Disks Associated with Sun-like stars

We present the discovery of debris systems around three solar mass stars based upon observations performed with the Spitzer Space Telescope as part of a Legacy Science Program, ``the Formation and Evolution of Planetary Systems'' (FEPS). We also confirm the presence of debris around two other stars. All the stars exhibit infrared emission in excess of the expected photospheres in the 70 micron band, but are consistent with photospheric emission at <= 33 micron. This restricts the maximum temperature of debris in equilibrium with the stellar radiation to T < 70 K. We find that these sources are relatively old in the FEPS sample, in the age range 0.7 - 3 Gyr. Based on models of the spectral energy distributions, we suggest that these debris systems represent materials generated by collisions of planetesimal belts. We speculate on the nature of these systems through comparisons to our own Kuiper Belt, and on the likely planet(s) responsible for stirring the system and ultimately releasing dust through collisions. We further report observations of a nearby star HD 13974 (d =11 pc) that is indistinguishable from a bare photosphere at both 24 micron and 70 micron. The observations place strong upper limits on the presence of any cold dust in this nearby system (L_IR/L_* < 10^{-5.2}).Comment: 31 pages, 9 figures, accepted for publication in Ap

Dreaming of drams: Authenticity in Scottish whisky tourism as an expression of unresolved Habermasian rationalities

In this paper, the production of whisky tourism at both independently owned and corporately owned distilleries in Scotland is explored by focusing on four examples (Arran, Glengoyne, Glenturret and Bruichladdich). In particular, claims of authenticity and Scottishness of Scottish whiskies through commercial materials, case studies, website-forum discussions and 'independent' writing about such whisky are analysed. It is argued that the globalisation and commodification of whisky and whisky tourism, and the communicative backlash to these trends typified by the search for authenticity, is representative of a Habermasian struggle between two irreconcilable rationalities. This paper will demonstrate that the meaning and purpose of leisure can be understood through such explorations of the tension between the instrumentality of commodification and the freedom of individuals to locate their own leisure lives in the lifeworld that remains. © 2011 Taylor & Francis

A dual role for prediction error in associative learning

Confronted with a rich sensory environment, the brain must learn statistical regularities across sensory domains to construct causal models of the world. Here, we used functional magnetic resonance imaging and dynamic causal modeling (DCM) to furnish neurophysiological evidence that statistical associations are learnt, even when task-irrelevant. Subjects performed an audio-visual target-detection task while being exposed to distractor stimuli. Unknown to them, auditory distractors predicted the presence or absence of subsequent visual distractors. We modeled incidental learning of these associations using a Rescorla--Wagner (RW) model. Activity in primary visual cortex and putamen reflected learning-dependent surprise: these areas responded progressively more to unpredicted, and progressively less to predicted visual stimuli. Critically, this prediction-error response was observed even when the absence of a visual stimulus was surprising. We investigated the underlying mechanism by embedding the RW model into a DCM to show that auditory to visual connectivity changed significantly over time as a function of prediction error. Thus, consistent with predictive coding models of perception, associative learning is mediated by prediction-error dependent changes in connectivity. These results posit a dual role for prediction-error in encoding surprise and driving associative plasticity

The role of functional single nucleotide polymorphisms of the human glucocorticoid receptor gene NR3C1 in Polish patients with bronchial asthma

N363S and ER22/23EK polymorphisms observed within glucocorticoid receptor gene (NR3C1) may play an important role in the development of bronchial asthma. NR3C1 gene is associated with an altered sensitivity to GCs. The aim of the research project was to study the correlation between this NR3C1 gene polymorphisms and occurrence of asthma in the population of Polish asthmatics. Peripheral blood was obtained from 207 healthy volunteers and 221 asthma patients. Genotyping was carried out with PCR-RFLP method. In the groups of patients with uncontrolled moderate asthma and uncontrolled severe disease, the genotype distribution for the investigated polymorphisms was as follows: N363S-AA, AG, GG occurring with 0.881/0.073/0.046 frequency and ER22/23EK-GG, GA, AA occurring with 0.963/0.037/0.000 frequency. Chi-square analysis revealed a significantly different (P < 0.05) distribution between cases and controls for the N363S polymorphisms. The N363S polymorphism of NR3C1 gene is significantly associated with bronchial asthma, susceptibility to the development of moderate to severe form of uncontrolled bronchial asthma

Feedback from the heart: emotional learning and memory is controlled by cardiac cycle, interoceptive accuracy and personality

Feedback processing is critical to trial-and-error learning. Here, we examined whether interoceptive signals concerning the state of cardiovascular arousal influence the processing of reinforcing feedback during the learning of ‘emotional’ face-name pairs, with subsequent effects on retrieval. Participants (N = 29) engaged in a learning task of face-name pairs (fearful, neutral, happy faces). Correct and incorrect learning decisions were reinforced by auditory feedback, which was delivered either at cardiac systole (on the heartbeat, when baroreceptors signal the contraction of the heart to the brain), or at diastole (between heartbeats during baroreceptor quiescence). We discovered a cardiac influence on feedback processing that enhanced the learning of fearful faces in people with heightened interoceptive ability. Individuals with enhanced accuracy on a heartbeat counting task learned fearful face-name pairs better when feedback was given at systole than at diastole. This effect was not present for neutral and happy faces. At retrieval, we also observed related effects of personality: First, individuals scoring higher for extraversion showed poorer retrieval accuracy. These individuals additionally manifested lower resting heart rate and lower state anxiety, suggesting that attenuated levels of cardiovascular arousal in extraverts underlies poorer performance. Second, higher extraversion scores predicted higher emotional intensity ratings of fearful faces reinforced at systole. Third, individuals scoring higher for neuroticism showed higher retrieval confidence for fearful faces reinforced at diastole. Our results show that cardiac signals shape feedback processing to influence learning of fearful faces, an effect underpinned by personality differences linked to psychophysiological arousal

Synthesis and Assessment Product

This Synthesis and Assessment Product is an important revision to the conclusions of earlier reports from the U.S. National Research Council and the Intergovernmental Panel on Climate Change. Previously reported discrepancies between the amount of warming near the surface and higher in the atmosphere have been used to challenge the reliability of climate models and the reality of human-induced global warming. Specifically, surface data showed substantial global-average warming, while early versions of satellite and radiosonde data showed little or no warming above the surface. This significant discrepancy no longer exists because errors in the satellite and radiosonde data have been identified and corrected. New data sets have also been developed that do not show such discrepancies. This Synthesis and Assessment Product is an important revision to the conclusions of earlier reports from the U.S. National Research Council and the Intergovernmental Panel on Climate Change. For recent decades, all current atmospheric data sets now show global-average warming that is similar to the surface warming. While these data are consistent with the results from climate models at the global scale, discrepancies in the tropics remain to be resolved. Nevertheless, the most recent observational and model evidence has increased confidence in our understanding of observed climatic changes and their causes