Na,K-ATPase is an essential gene maintaining electrochemical gradients across the plasma membrane. Although previous studies have intensively focused on the role of Na,K-ATPase in regulating cardiac function in the adults, little is known about the requirement for Na,KATPase during embryonic heart development. Here, we report the identification of a zebrafish mutant, heart and mind, which exhibits multiple cardiac defects, including the primitive heart tube extension abnormality, aberrant cardiomyocyte differentiation, and reduced heart rate and contractility. Molecular cloning reveals that the heart and mind lesion resides in the α1B1 isoform of Na,K-ATPase. Blocking Na,K-ATPase α1B1 activity by pharmacological means or by morpholino antisense oligonucleotides phenocopies the patterning and functional defects of heart and mind mutant hearts, suggesting crucial roles for Na,KATPase α1B1 in embryonic zebrafish hearts. In addition to α1B1, the Na,K-ATPase α2 isoform is required for embryonic cardiac patterning. Although the α1B1 and α2 isoforms share high degrees of similarities in their coding sequences, they have distinct roles in patterning zebrafish hearts. The phenotypes of heart and mind mutants can be rescued by supplementing α1B1, but not α2, mRNA to the mutant embryos, demonstrating that α1B1 and α2 are not functionally equivalent. Furthermore, instead of interfering with primitive heart tube formation or cardiac chamber differentiation, blocking the translation of Na,KATPase α2 isoform leads to cardiac laterality defects. Supplemental figure available online
Our ability to generate well-timed sequences of movements is critical to an array of behaviors, including the ability to play a musical instrument or a video game. Here we address two questions relating to timing with the goal of better understanding the neural mechanisms underlying temporal processing. First, how does accuracy and variance change over the course of learning of complex spatiotemporal patterns? Second, is the timing of sequential responses most consistent with starting and stopping an internal timer at each interval or with continuous timing? To address these questions we used a psychophysical task in which subjects learned to reproduce a sequence of finger taps in the correct order and at the correct times – much like playing a melody at the piano. This task allowed us to calculate the variance of the responses at different time points using data from the same trials. Our results show that while “standard” Weber’s law is clearly violated, variance does increase as a function of time squared, as expected according to the generalized form of Weber’s law – which separates the source of variance into time-dependent and time-independent components. Over the course of learning, both the time-independent variance and the coefficient of the time-dependent term decrease. Our analyses also suggest that timing of sequential events does not rely on the resetting of an internal timer at each event. We describe and interpret our results in the context of computer simulations that capture some of our psychophysical findings. Specifically, we show that continuous timing, as opposed to “reset” timing, is consistent with “population clock” models in which timing emerges from the internal dynamics of recurrent neural networks.
Innate behavioral reactions to sensory stimuli may be subject to modulation by contextual conditions including signals from other modalities. Whereas sensory processing by individual modalities has been well-studied, the cell circuit mechanisms by which signals from different sensory systems are integrated to control behavior remains poorly understood. Here, we provide a new behavioral model to study the mechanisms of multisensory integration. This behavior, which we termed odor-induced visual valence reversal, occurs when the innate avoidance response to a small moving object by flying Drosophila melanogaster is reversed by the presence of an appetitive odor. Instead of steering away from the small object representing an approaching threat, flies begin to steer towards the object in the presence of odor. Odor-induced visual valence reversal occurs rapidly without associative learning and occurs for attractive odors including apple cider vinegar and ethanol, but not for innately aversive benzaldehyde. Optogenetic activation of octopaminergic neurons robustly induces visual valence reversal in the absence of odor, as does optogenetic activation of directional columnar motion detecting neurons that express octopamine receptors. Optogenetic activation of octopamine neurons drives calcium responses in the motion detectors. Taken together, our results implicate a multisensory processing cascade in which appetitive odor activates octopaminergic neuromodulation of visual pathways, which leads to increased visual saliency and the switch from avoidance to approach toward a small visual object.
Lack of resources and exposure to neuroscience in K-12 education has resulted in a limited number of K-12 students pursuing higher education in the field. Meanwhile, the rapid expansion of the field of neuroscience has encouraged many higher educational institutes to offer neuroscience majors. This has opened up the opportunity to engage faculty, as well as graduate and undergraduate students in bringing the most needed knowledge and awareness about neuroscience into K-12 classrooms.However, undergraduate neuroscience curricula have limited formal opportunities to engage in outreach, and few existing programs have assessments to determine their effectiveness. To address these needs, we developed quantitative assessment tools that complement an existing neuroscience outreach program-Project Brainstormat the University of California, Los Angeles (UCLA). 29 UCLA undergraduates enrolled in the 2016 and 2017 programs participated in this study, along with 298 K-12 students from local schools across the Los Angeles area. In undergraduate students, we assessed (a) improvement in students' teaching/communication abilities across the course of the outreach program, and (b) confidence in explaining neuroscience topics and interest in pursuing teaching career. In K-12 students, we evaluated (a) knowledge gain in neuroscience topics and (b) interest in pursuing higher education.Overall, Project Brainstorm showed significant improvement in all the
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