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.

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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

Animals classify stimuli to generate appropriate motor actions. In flight, Drosophila melanogaster classify equidistant large and small objects with categorically different behaviors: a tall object evokes approach whereas a small object elicits avoidance. We studied visuomotor behavior in rigidly and magnetically tethered D. melanogaster to reveal strategies that generate aversion to a small object. We discovered that small-object aversion in tethered flight is enabled by aversive saccades and smooth movement, which vary with the stimulus type. Aversive saccades in response to a short bar had different dynamics from approach saccades in response to a tall bar and the distribution of pre-saccade error angles was more stochastic for a short bar. Taken together, we show that aversive responses in D. melanogaster are driven in part by processes that elicit signed saccades with distinct dynamics and trigger mechanisms. Our work generates new hypotheses to study brain circuits that underlie classification of objects in D. melanogaster.

Highlights d A fly's innate aversion to a small visual object is reversed by odor d Object valence is reversed by attractive odors but not an aversive one d Activating octopaminergic neurons is sufficient to reverse object valence d Motion-detecting neurons are necessary and sufficient to reverse object valence

Movement and behavioral state influence perception, and a stimulus can elicit opposite behavioral actions depending on whether the animal is moving toward or away from it. Here, we use fast wholebrain lightfield imaging in adult Drosophila melanogaster to analyze the relationship between movement and neuronal activity. Using pan-neuronal calcium imaging, we observe brainwide neuronal activity that tightly correlated with spontaneous bouts of movement. Imaging of specific sets of neurons across the brain reveals that both excitatory and inhibitory as well as different types of neuromodulatory neurons are active during walk inconsistent with a reduction of inhibition on neuronal activity. While most neuron types are activated at walk-onset, serotonergic neurons show more complex patterns of activity with neurons in several brain regions being inhibited during walk. Using available anatomical data, we map forward running and turning-induced activity onto different brain subregions and sometimes individual neurons. Moreover, we find that spontaneous walk and forced walk elicit highly similar wholebrain activity suggesting that a large part of the observed activity corresponds to walk itself rather than its initiation by higher brain centers. Based on our data, we conclude that movement and movement-related sensory feedback signals originating in the ventral nerve cord induce wide-spread activity in the brain allowing the integration of behavioral state into most or all brain processes.