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6 Publications
Showing 1-6 of 6 resultsResponses to threat-related stimuli are influenced by conscious and unconscious processes, but the neural systems underlying these processes and their relationship to anxiety have not been clearly delineated. Using fMRI, we investigated the neural responses associated with the conscious and unconscious (backwardly masked) perception of fearful faces in healthy volunteers who varied in threat sensitivity (Spielberger trait anxiety scale). Unconscious processing modulated activity only in the basolateral subregion of the amygdala, while conscious processing modulated activity only in the dorsal amygdala (containing the central nucleus). Whereas activation of the dorsal amygdala by conscious stimuli was consistent across subjects and independent of trait anxiety, activity in the basolateral amygdala to unconscious stimuli, and subjects’ reaction times, were predicted by individual differences in trait anxiety. These findings provide a biological basis for the unconscious emotional vigilance characteristic of anxiety and a means for investigating the mechanisms and efficacy of treatments for anxiety.
BAF and PBAF are two related mammalian chromatin remodeling complexes essential for gene expression and development. PBAF, but not BAF, is able to potentiate transcriptional activation in vitro mediated by nuclear receptors, such as RXRalpha, VDR, and PPARgamma. Here we show that the ablation of PBAF-specific subunit BAF180 in mouse embryos results in severe hypoplastic ventricle development and trophoblast placental defects, similar to those found in mice lacking RXRalpha and PPARgamma. Embryonic aggregation analyses reveal that in contrast to PPARgamma-deficient mice, the heart defects are likely a direct result of BAF180 ablation, rather than an indirect consequence of trophoblast placental defects. We identified potential target genes for BAF180 in heart development, such as S100A13 as well as retinoic acid (RA)-induced targets RARbeta2 and CRABPII. Importantly, BAF180 is recruited to the promoter of these target genes and BAF180 deficiency affects the RA response for CRABPII and RARbeta2. These studies reveal unique functions of PBAF in cardiac chamber maturation.
The efficient silylation of alcohols with di- and trialkynylsilanes was achieved under base-catalyzed conditions to afford alkynyl silyl ethers and symmetrical alkynyl silaketals in good yield. A selective alcoholysis of dialkynyl silyl ethers to mixed silaketals was also demonstrated. These products served as substrates for enyne ring-closing metathesis and, consequently, as precursors to stereochemically defined 1,3-dienes.
Under certain conditions, regenerative voltage spikes can be initiated locally in the dendrites of CA1 pyramidal neurons. These are interesting events that could potentially provide neurons with additional computational abilities. Using whole-cell dendritic recordings from the distal apical trunk and proximal tuft regions and realistic computer modeling, we have determined that highly synchronized and moderately clustered inputs are required for dendritic spike initiation: approximately 50 synaptic inputs spread over 100 mum of the apical trunk/tuft need to be activated within 3 msec. Dendritic spikes are characterized by a more depolarized voltage threshold than at the soma [-48 +/- 1 mV (n = 30) vs -56 +/- 1 mV (n = 7), respectively] and are mainly generated and shaped by dendritic Na+ and K+ currents. The relative contribution of AMPA and NMDA currents is also important in determining the actual spatiotemporal requirements for dendritic spike initiation. Once initiated, dendritic spikes can easily reach the soma, but their propagation is only moderately strong, so that it can be modulated by physiologically relevant factors such as changes in the V(m) and the ionic composition of the extracellular solution. With effective spike propagation, an extremely short-latency neuronal output is produced for greatly reduced input levels. Therefore, dendritic spikes function as efficient detectors of specific input patterns, ensuring that the neuronal response to high levels of input synchrony is a precisely timed action potential output.
Does the C. elegans nervous system contain multi-neuron computational modules that perform stereotypical functions? We attempt to answer this question by searching for recurring multi-neuron inter-connectivity patterns in the C. elegans nervous system’s wiring diagram.
Drosophila has been developed recently as a model system to investigate the molecular and neural mechanisms underlying responses to drugs of abuse. Genetic screens for mutants with altered drug-induced behaviors thus provide an unbiased approach to define novel molecules involved in the process. We identified mutations in the Drosophila LIM-only (LMO) gene, encoding a regulator of LIM-homeodomain proteins, in a genetic screen for mutants with altered cocaine sensitivity. Reduced Lmo function increases behavioral responses to cocaine, while Lmo overexpression causes the opposite effect, reduced cocaine responsiveness. Expression of Lmo in the principal Drosophila circadian pacemaker cells, the PDF-expressing ventral lateral neurons (LN(v)s), is sufficient to confer normal cocaine sensitivity. Consistent with a role for Lmo in LN(v)function,Lmomutants also show defects in circadian rhythms of behavior. However, the role for LN(v)s in modulating cocaine responses is separable from their role as pacemaker neurons: ablation or functional silencing of the LN(v)s reduces cocaine sensitivity, while loss of the principal circadian neurotransmitter PDF has no effect. Together, these results reveal a novel role for Lmo in modulating acute cocaine sensitivity and circadian locomotor rhythmicity, and add to growing evidence that these behaviors are regulated by shared molecular mechanisms. The finding that the degree of cocaine responsiveness is controlled by the Drosophila pacemaker neurons provides a neuroanatomical basis for this overlap. We propose that Lmo controls the responsiveness of LN(v)s to cocaine, which in turn regulate the flies’ behavioral sensitivity to the drug.