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Biology subjects

Wallace, R. S.

Publications and source records attributed to Wallace, R. S..

2 recordsLinked to original sources

Mapping patterns of thought onto brain activity during movie-watching

Movie-watching is a central aspect of our lives and an important paradigm for understanding the brain mechanisms behind cognition as it occurs in daily life. Contemporary views of ongoing thought argue that the ability to make sense of events in the here and now depend on the neural processing of incoming sensory information by auditory and visual cortex, which are kept in check by systems in association cortex. However, we currently lack an understanding of how patterns of ongoing thoughts map onto the different brain systems when we watch a film, partly because methods of sampling experience disrupt the dynamics of brain activity and the experience of movie-watching. Our study established a novel method for mapping thought patterns onto the brain activity that occurs at different moments of a film, which does not disrupt the time course of brain activity or the movie-watching experience. We found moments when experience sampling highlighted engagement with multi-sensory features of the film or highlighted thoughts with episodic features, regions of sensory cortex were more active and subsequent memory for events in the movie was better--on the other hand, periods of intrusive distraction emerged when activity in regions of association cortex within the frontoparietal system was reduced. These results highlight the critical role sensory systems play in the multi- modal experience of movie-watching and provide evidence for the role of association cortex in reducing distraction when we watch films. Significance statementStates like movie-watching provide a window into the brain mechanisms behind cognition in daily life. However, we know relatively little about the mapping between brain activity during movies and associated thought patterns because of difficulties in measuring cognition without disrupting how brain activity naturally unfolds. We establish a novel method to link different experiential states to brain activity during movie-watching with minimal interruptions to viewers or disruptions to brain dynamics. We found states of sensory engagement occur in moments of films when activity in visual and auditory cortex are high. In contrast, states of distraction are reduced when activity in frontoparietal regions is high. Our study, therefore, establishes both sensory and association cortex as core features of the movie-watching experience.

neuroscience↗

Nitric Oxide modulates spontaneous Ca2+ release and ventricular arrhythmias during β adrenergic signalling through S-nitrosylation of Calcium/Calmodulin dependent kinase II

RationaleNitric oxide (NO) has been identified as a signalling molecule generated during {beta}-adrenergic receptor (AR) stimulation in the heart. Furthermore, a role for NO in triggering spontaneous Ca2+ release via S-nitrosylation of Ca2+/calmodulin kinase II delta (CaMKII{delta}) is emerging. NO donors are routinely used clinically for their cardioprotective effects in the heart, but it is unknown how NO donors modulate the pro-arrhythmic CaMKII to alter cardiac arrhythmia incidence. ObjectiveWe test the role of S-nitrosylation of CaMKII{delta} at the Cys-273 inhibitory site and Cys-290 activating site in cardiac Ca2+ handling and arrhythmogenesis before and during {beta}-AR stimulation. Methods and ResultsWe measured Ca2+-handling in isolated cardiomyocytes from C57BL/6J wild-type (WT) mice and mice lacking CaMKII{delta} expression (CaMKII{delta}-KO) or with deletion of the S-nitrosylation site on CaMKII{delta} at Cys-273 or Cys-290 (CaMKII{delta}-C273S and -C290A knock-in mice). Cardiomyocytes were exposed to NO donors, S-nitrosoglutathione (GSNO; 150 M), sodium nitroprusside (SNP; 200 M) and/or {beta}-adrenergic agonist isoproterenol (ISO; 100 nM). WT and CaMKII{delta}-KO cardiomyocytes treated with GSNO showed no change in Ca2+ transient or spark properties under baseline conditions (0.5 Hz stimulation frequency). Both WT and CaMKII{delta}-KO cardiomyocytes responded to ISO with a full inotropic and lusitropic Ca2+ transient response as well as increased Ca2+ spark frequency. However, the increase in Ca2+ spark frequency was significantly attenuated in CaMKII{delta}-KO cardiomyocytes. The protection from ISO-induced Ca2+ sparks and waves was mimicked by GSNO pre-treatment in WT cardiomyocytes, but lost in CaMKII{delta}-C273S cardiomyocytes that displayed a robust increase in Ca2+ waves. This observation is consistent with CaMKII{delta}-C273 S-nitrosylation being critical in limiting ISO-induced arrhythmogenic sarcoplasmic reticulum Ca2+ leak. When GSNO was applied after ISO this protection was not observed in WT or CaMKII{delta}-C273S but was apparent in CaMKII{delta}-C290A. In Langendorff-perfused isolated hearts, GSNO pre-treatment limited ISO-induced arrhythmias in WT but not CaMKII{delta}-C273S hearts, while GSNO exposure after ISO sustained or exacerbated arrhythmic events. ConclusionsWe conclude that prior S-nitrosylation of CaMKII{delta} at Cys-273 can limit subsequent {beta}-AR induced arrhythmias, but that S-nitrosylation at Cys-290 might worsen or sustain {beta}-AR-induced arrhythmias. This has important implications for the administration of NO donors in the clinical setting.

physiology↗