1,146,671 research outputs found

    Voltage-sensitive dye imaging reveals tonotopic organization of auditory cortex spontaneous activity

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    Imaging neural activity across a large (several mm) cortical area with high temporal and spatial resolution is desirable, for example in the auditory system to measure cortical processing across a broad frequency spectrum. Voltage-sensitive dye imaging (VSDI) has a unique combination of properties making this possible, but so far studies have been limited to studying simple sparsely-presented sensory stimuli. We demonstrate the feasibility of long-acquisition VSDI (using the dye RH-1691) in auditory cortex while presenting complex time-varying acoustic stimuli or silence. Using a dense array of partially-overlapping 50 ms tone pips (8 frequencies per octave spanning six octaves), we obtained high-resolution spectrotemporal receptive fields (STRFs) simultaneously across the majority of the guinea pig primary auditory cortical fields (A1 and DC). Long epochs of spontaneous activity were also measured, permitting a comparison of spontaneous activity patterns with functional architecture. By grouping all pixels in areas A1 and DC according to sound frequency preference (obtained from STRFs), we reveal that spontaneous activity (such as cortical spindles) show complex spatial patterns, which are organized according to sound frequency preference within and across cortical areas. More specifically, spontaneous activity correlation decreases as frequency preference diverges within A1 or DC; but additionally, pixels in A1 are also highly correlated with (even far-away) pixels in DC sharing similar frequency preference. These properties of patterned cortical spontaneous activity constrain mechanistic hypotheses regarding their genesis. Beyond these observations, the feasibility of VSDI with continuous stimulation or silence permits measuring population activity during long-lasting sound patterns, which is necessary for examining cortical dynamics and sensory-context dependent processing

    Dorsal-CA1 hippocampal neuronal ensembles encode nicotine-reward contextual associations

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    Natural and drug rewards increase the motivational valence of stimuli in the environment that, through Pavlovian learning mechanisms, become conditioned stimuli that directly motivate behavior in the absence of the original unconditioned stimulus. While the hippocampus has received extensive attention for its role in learning and memory processes, less is known regarding its role in drug-reward associations. We used in vivo Ca2+ imaging in freely moving mice during the formation of nicotine preference behavior to examine the role of the dorsal-CA1 region of the hippocampus in encoding contextual reward-seeking behavior. We show the development of specific neuronal ensembles whose activity encodes nicotine-reward contextual memories and that are necessary for the expression of place preference. Our findings increase our understanding of CA1 hippocampal function in general and as it relates to reward processing by identifying a critical role for CA1 neuronal ensembles in nicotine place preference

    Preferences for Government Size and their Effect on Labor-Leisure Decisions

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    While many economists have theorized and/or empirically demonstrated that labor-leisure decisions are influenced by the rate of taxation, this note introduces a new mechanism in which the collecting of taxes on income may affect such decisions. Although standard models assume that agents have no preference for the size and scope of government activity, recent and past political rhetoric suggests that preferences do exist. We examine how labor-leisure decisions can be affected when taxes are derived from income and agents' utility functions include a preference for government size.

    Bending arms, bending discounting functions. How motor actions affect intertemporal decision-making.

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    In five studies we demonstrate that task-irrelevant somatic activity influences intertemporal decision making: Arm movements associated with approach (arm flexion), rather than avoidance (arm extension), instigate present-biased preferences. We show that the preference for immediate over delayed gratification is moderated by the sensitivity of the approach system and, owing to learning principles, restricted to arm positions of the dominant hand. This research extends the effects of somatic activity beyond attitude formation and cognition, and provides empirical evidence for the effect of somatic activity on motivational systems.

    Functional characterization of a melon alcohol acyl-transferase gene family involved in the biosynthesis of ester volatiles. Identification of the crucial role of a threonine residue for enzyme activity

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    Volatile esters, a major class of compounds contributing to the aroma of many fruit, are synthesized by alcohol acyl-transferases (AAT). We demonstrate here that, in Charentais melon (Cucumis melo var. cantalupensis), AAT are encoded by a gene family of at least four members with amino acid identity ranging from 84% (Cm-AAT1/Cm-AAT2) and 58% (Cm-AAT1/Cm-AAT3) to only 22% (Cm-AAT1/Cm-AAT4). All encoded proteins, except Cm-AAT2, were enzymatically active upon expression in yeast and show differential substrate preferences. Cm-AAT1 protein produces a wide range of short and long-chain acyl esters but has strong preference for the formation of E-2-hexenyl acetate and hexyl hexanoate. Cm-AAT3 also accepts a wide range of substrates but with very strong preference for producing benzyl acetate. Cm-AAT4 is almost exclusively devoted to the formation of acetates, with strong preference for cinnamoyl acetate. Site directed mutagenesis demonstrated that the failure of Cm-AAT2 to produce volatile esters is related to the presence of a 268-alanine residue instead of threonine as in all active AAT proteins. Mutating 268-A into 268-T of Cm-AAT2 restored enzyme activity, while mutating 268-T into 268-A abolished activity of Cm-AAT1. Activities of all three proteins measured with the prefered substrates sharply increase during fruit ripening. The expression of all Cm-AAT genes is up-regulated during ripening and inhibited in antisense ACC oxidase melons and in fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. The data presented in this work suggest that the multiplicity of AAT genes accounts for the great diversity of esters formed in melon

    Fluorescence-based incision assay for human XPF-ERCC1 activity identifies important elements of DNA junction recognition

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    The structure-specific endonuclease activity of the human XPF–ERCC1 complex is essential for a number of DNA processing mechanisms that help to maintain genomic integrity. XPF–ERCC1 cleaves DNA structures such as stem–loops, bubbles or flaps in one strand of a duplex where there is at least one downstream single strand. Here, we define the minimal substrate requirements for cleavage of stem–loop substrates allowing us to develop a real-time fluorescence-based assay to measure endonuclease activity. Using this assay, we show that changes in the sequence of the duplex upstream of the incision site results in up to 100-fold variation in cleavage rate of a stem-loop substrate by XPF-ERCC1. XPF–ERCC1 has a preference for cleaving the phosphodiester bond positioned on the 3′-side of a T or a U, which is flanked by an upstream T or U suggesting that a T/U pocket may exist within the catalytic domain. In addition to an endonuclease domain and tandem helix–hairpin–helix domains, XPF has a divergent and inactive DEAH helicase-like domain (HLD). We show that deletion of HLD eliminates endonuclease activity and demonstrate that purified recombinant XPF–HLD shows a preference for binding stem–loop structures over single strand or duplex alone, suggesting a role for the HLD in initial structure recognition. Together our data describe features of XPF–ERCC1 and an accepted model substrate that are important for recognition and efficient incision activity
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