Summary The roundworm C. elegans is widely used as an aging model, with hundreds of genes identified that modulate aging(Kaeberlein et al. 2002). The development and bodyplan of the 959 cells comprising the adult have been well described and established for more than 25 years(Sulston & Horvitz 1977; Sulston et al. 1983). However, morphological changes with age in this optically transparent animal are less well understood, with only a handful of studies investigating the pathobiology of aging. Age related changes in muscle(Herndon et al. 2002), neurons(Herndon et al. 2002), intestine and yolk granules(Garigan et al. 2002; Herndon et al. 2002), nuclear architecture(Haithcock et al. 2005), tail nuclei(Golden et al. 2007), and the germline(Golden et al. 2007) have been observed via a variety of traditional relatively low-throughput methods. We report here a number of novel approaches to study the pathobiology of aging C. elegans. We combined histological staining of serial-sectioned tissues, transmission electron microscopy, and confocal microscopy with 3-D volumetric reconstructions, and characterized age-related morphological changes of multiple wild-type individuals at different ages. This enabled us to identify several novel pathologies with age in the C. elegans intestine, including loss of critical nuclei, degradation of intestinal microvilli, changes in the size, shape, and cytoplasmic contents of the intestine, and altered morphologies due to ingested bacteria. The three-dimensional models we have created of tissues and cellular components from multiple individuals of different ages, represent a unique resource to demonstrate global heterogeneity of a multi-cellular organism.

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Although it is well established that multiple frontal, parietal and occipital regions in humans are involved in anticipatory deployment of visual spatial attention, less is known about the electrophysiological signals in each region across multiple sub-second periods of attentional deployment. We used MEG measures of cortical stimulus-locked, signal-averaged (ERF) activity during a task in which a symbolic cue directed covert attention to the relevant location on each trial. Direction-specific attention effects occurred in different cortical regions for each of multiple time periods during the delay between the cue and imperative stimulus. A sequence of activation from V1/V2 to extrastriate, parietal and frontal regions occurred within 110 ms post-cue, possibly related to extraction of cue meaning. Direction-specific activations ~300 ms post-cue in FEF, LIP and Cuneus support early covert targeting of the cued location. This was followed by co-activation of a frontal-parietal system (SFG, MFG, LIP, IPSa, LIP) that may coordinate the transition from targeting the cued location to sustained deployment of attention to both space and feature in the last period. The last periodinvolved direction-specific activity in parietal regions and both dorsal and ventral sensory regions (LIP, IPSa, IPSv, LO, Fusiform), which was accompanied by activation that was not direction-specific in right hemisphere frontal regions (FEF, SFG, MFG). Behavioral performance corresponded with the magnitude of attention-related activity in different brain regions at each time period during deployment. The results add to the emerging electrophysiological characterization of different cortical networks that operate during anticipatory deployment of visual spatial attention.

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