Anticipation to Social and Nonsocial Dynamic Cues in Preschool-Age Children.

The ability to learn from expectations is foundational to social and nonsocial learning in children. However, we know little about the brain basis of reward expectation in development. Here, 3- to 4-year-olds (N = 26) were shown a passive associative learning paradigm with dynamic stimuli. Anticipation for reward-related stimuli was measured via the stimulus preceding negativity (SPN). To our knowledge, this is the first study to measure an SPN in children younger than age 6. Our findings reveal distinct anticipatory neural signatures for social versus nonsocial stimuli, consistent with previous research in older children. This study suggests an SPN can be elicited in preschoolers and is larger for social than nonsocial stimuli.

Thinking Counterfactually Supports Children's Evidence Evaluation in Causal Learning.

Often, the evidence we observe is consistent with more than one explanation. How do learners discriminate among candidate causes? The current studies examine whether counterfactuals help 5-year olds (N = 120) select between competing hypotheses and compares the effectiveness of these prompts to a related scaffold. In Experiment 1, counterfactuals support evidence evaluation, leading children to privilege and extend the cause that accounted for more data. In Experiment 2, the hypothesis that accounted for the most evidence was pitted against children's prior beliefs. Children who considered alternative outcomes privileged the hypothesis that accounted for more observations, whereas those who explained relied on prior beliefs. Findings demonstrate that counterfactuals recruit attention to disambiguating evidence and outperform explanation when data contrast with existing beliefs.

Evolutionarily conserved regulation of sleep by epidermal growth factor receptor signaling.

The genetic bases for most human sleep disorders and for variation in human sleep quantity and quality are largely unknown. Using the zebrafish, a diurnal vertebrate, to investigate the genetic regulation of sleep, we found that epidermal growth factor receptor (EGFR) signaling is necessary and sufficient for normal sleep levels and is required for the normal homeostatic response to sleep deprivation. We observed that EGFR signaling promotes sleep via mitogen-activated protein kinase/extracellular signal-regulated kinase and RFamide neuropeptide signaling and that it regulates RFamide neuropeptide expression and neuronal activity. Consistent with these findings, analysis of a large cohort of human genetic data from participants of European ancestry revealed that common variants in genes within the EGFR signaling pathway are associated with variation in human sleep quantity and quality. These results indicate that EGFR signaling and its downstream pathways play a central and ancient role in regulating sleep and provide new therapeutic targets for sleep disorders.

Genetic and neuronal regulation of sleep by neuropeptide VF.

Sleep is an essential and phylogenetically conserved behavioral state, but it remains unclear to what extent genes identified in invertebrates also regulate vertebrate sleep. RFamide-related neuropeptides have been shown to promote invertebrate sleep, and here we report that the vertebrate hypothalamic RFamide neuropeptide VF (NPVF) regulates sleep in the zebrafish, a diurnal vertebrate. We found that NPVF signaling and npvf-expressing neurons are both necessary and sufficient to promote sleep, that mature peptides derived from the NPVF preproprotein promote sleep in a synergistic manner, and that stimulation of npvf-expressing neurons induces neuronal activity levels consistent with normal sleep. These results identify NPVF signaling and npvf-expressing neurons as a novel vertebrate sleep-promoting system and suggest that RFamide neuropeptides participate in an ancient and central aspect of sleep control.

A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States.

Neuromodulation of arousal states ensures that an animal appropriately responds to its environment and engages in behaviors necessary for survival. However, the molecular and circuit properties underlying neuromodulation of arousal states such as sleep and wakefulness remain unclear. To tackle this challenge in a systematic and unbiased manner, we performed a genetic overexpression screen to identify genes that affect larval zebrafish arousal. We found that the neuropeptide neuromedin U (Nmu) promotes hyperactivity and inhibits sleep in zebrafish larvae, whereas nmu mutant animals are hypoactive. We show that Nmu-induced arousal requires Nmu receptor 2 and signaling via corticotropin releasing hormone (Crh) receptor 1. In contrast to previously proposed models, we find that Nmu does not promote arousal via the hypothalamic-pituitary-adrenal axis, but rather probably acts via brainstem crh-expressing neurons. These results reveal an unexpected functional and anatomical interface between the Nmu system and brainstem arousal systems that represents a novel wake-promoting pathway.