ABSTRACT
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ABSTRACT
Attending to targets in a detection task can facilitate memory for concurrently presented information, a phenomenon known as the attentional boost effect. One account of the attentional boost suggests that it reflects the temporal selection of behaviorally relevant moments, broadly facilitating the processing of information encountered at these times. Because pupil diameter increases when orienting to behaviorally relevant events and is positively correlated with increases in gain and activity in the locus coeruleus (a purported neurophysiological mechanism for temporal selection), we tested whether the attentional boost effect is accompanied by an increase in pupil diameter. Participants memorized a series of individually presented scenes. Whenever a scene appeared, a high or low pitched tone was played, and participants counted (and later reported) the number of tones in the pre-specified, target pitch. Target detection enhanced later memory for concurrently presented scenes. It was accompanied by a larger pupil response than was distractor rejection, and this effect was more pronounced for subsequently remembered rather than forgotten scenes. Thus, conditions that produce the attentional boost effect may also elicit phasic changes in neural gain and locus coeruleus activity.
Subject(s)
Memory/physiology , Pupil/physiology , Adolescent , Adult , Attention/physiology , Female , Humans , Locus Coeruleus/physiology , Male , Psychomotor Performance/physiology , Young AdultABSTRACT
Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used treatment for life-threatening conditions such as leukaemia; however, the molecular mechanisms regulating HSPC engraftment of the recipient niche remain incompletely understood. Here we develop a competitive HSPC transplant method in adult zebrafish, using in vivo imaging as a non-invasive readout. We use this system to conduct a chemical screen, and identify epoxyeicosatrienoic acids (EETs) as a family of lipids that enhance HSPC engraftment. The pro-haematopoietic effects of EETs were conserved in the developing zebrafish embryo, where 11,12-EET promoted HSPC specification by activating a unique activator protein 1 (AP-1) and runx1 transcription program autonomous to the haemogenic endothelium. This effect required the activation of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway, specifically PI(3)Kγ. In adult HSPCs, 11,12-EET induced transcriptional programs, including AP-1 activation, which modulate several cellular processes, such as migration, to promote engraftment. Furthermore, we demonstrate that the EET effects on enhancing HSPC homing and engraftment are conserved in mammals. Our study establishes a new method to explore the molecular mechanisms of HSPC engraftment, and discovers a previously unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic generation and regeneration processes. EETs may have clinical application in marrow or cord blood transplantation.