Bridging gaps in traditional research training with iBiology Courses.

iBiology Courses provide trainees with just-in-time learning resources to become effective researchers. These courses can help scientists build core research skills, plan their research projects and careers, and learn from scientists with diverse backgrounds.

Preparing future STEM faculty through flexible teaching professional development.

We have prepared thousands of future STEM faculty around the world to adopt evidence-based instructional practices through their participation in two massive open online courses (MOOCs) and facilitated in-person learning communities. Our novel combination of asynchronous online and coordinated, structured face-to-face learning community experiences provides flexible options for STEM graduate students and postdoctoral fellows to pursue teaching professional development. A total of 14,977 participants enrolled in seven offerings of the introductory course held 2014-2018, with 1,725 participants (11.5% of enrolled) completing the course. Our results of high levels of engagement and learning suggest that leveraging the affordances of educational technologies and the geographically clustered nature of this learner demographic in combination with online flexible learning could be a sustainable model for large scale professional development in higher education. The preparation of future STEM faculty makes an important difference in establishing high-quality instruction that meets the diverse needs of all undergraduate students, and the initiative described here can serve as a model for increasing access to such preparation.

The Explorer's Guide to Biology: A Free Multimedia Educational Resource to Promote Deep Learning and Understanding of the Scientific Process.

Here, we describe a new open-access digital resource for teaching and learning life science, The Explorer's Guide to Biology (available at explorebiology.org). Biology can often feel like a daunting subject where learners must comprehend a sea of facts before they can participate in meaningful discussions regarding core biology concepts or biological research. In truth, developing an intellectual framework by learning how scientists solve complex biological questions may be more valuable than memorizing a sea of facts. Yet, there is a lack of free educational resources that address this issue or attempt to provide learners with context for the knowledge they are gaining. Our goal is to offer learners a more exciting and accurate window into the life sciences. Our content is designed to help learners educate themselves by engaging with stories of discovery that highlight the process of science. This strategy not only provides an intellectual framework for the content presented but also provides the learner with an accurate view of the process of science. We leverage multiple modes of content delivery (such as videos, images, text, interactive activities, and just-in-time assessments) to create an engaging learning experience and an easily adaptable teaching resource. The resource is targeted for undergraduate or AP high school-level life science educators and learners, however, it is designed so anyone who is interested in learning about life science can engage with the content with little to no prior knowledge.

Photoperiodic effects on monoamine signaling and gene expression throughout development in the serotonin and dopamine systems.

Photoperiod or the duration of daylight has been implicated as a risk factor in the development of mood disorders. The dopamine and serotonin systems are impacted by photoperiod and are consistently associated with affective disorders. Hence, we evaluated, at multiple stages of postnatal development, the expression of key dopaminergic (TH) and serotonergic (Tph2, SERT, and Pet-1) genes, and midbrain monoamine content in mice raised under control Equinox (LD 12:12), Short winter-like (LD 8:16), or Long summer-like (LD 16:8) photoperiods. Focusing in early adulthood, we evaluated the midbrain levels of these serotonergic genes, and also assayed these gene levels in the dorsal raphe nucleus (DRN) with RNAScope. Mice that developed under Short photoperiods demonstrated elevated midbrain TH expression levels, specifically during perinatal development compared to mice raised under Long photoperiods, and significantly decreased serotonin and dopamine content throughout the course of development. In adulthood, Long photoperiod mice demonstrated decreased midbrain Tph2 and SERT expression levels and reduced Tph2 levels in the DRN compared Short photoperiod mice. Thus, evaluating gene × environment interactions in the dopaminergic and serotonergic systems during multiple stages of development may lead to novel insights into the underlying mechanisms in the development of affective disorders.

Sequential Photoperiodic Programing of Serotonin Neurons, Signaling and Behaviors During Prenatal and Postnatal Development.

Early life stimuli during critical developmental time frames have been linked to increased risk for neurodevelopmental disorders later in life. The serotonergic system of the brain is implicated in mood disorders and is impacted by the duration of daylight, or photoperiod. Here we sought to investigate sensitive periods of prenatal and postnatal development for photoperiodic programming of DRN serotonin neurons, midbrain serotonin and metabolite levels along with affective behaviors in adolescence (P30) or adulthood (P50). To address these questions we restricted the interval of exposure to prenatal development (E0-P0) for Long summer-like photoperiods (LD 16:8), or Short winter-like photoperiods (LD 8:16) with postnatal development and maturation then occurring under the opposing photoperiod. Prenatal exposure alone to Long photoperiods was sufficient to fully program increased excitability of DRN serotonin neurons into adolescence and adulthood, similar to maintained exposure to Long photoperiods throughout development. Interestingly, Long photoperiod exposure can elevate serotonin and its' corresponding metabolite levels along with reducing affective behavior, which appear to have both pre and postnatal origins. Thus, exposure to Long photoperiods prenatally programs increased DRN serotonin neuronal excitability, but this step is insufficient to program serotonin signaling and affective behavior. Continuing influence of Long photoperiods during postnatal development then modulates serotonergic content and has protective effects for depressive-like behavior. Photoperiodic programing of serotonin function in mice appears to be a sequential process with programing of neuronal excitability as a first step occurring prenatally, while programing of circuit level serotonin signaling and behavior extends into the postnatal period.

Pet-1 Switches Transcriptional Targets Postnatally to Regulate Maturation of Serotonin Neuron Excitability.

Newborn neurons enter an extended maturation stage, during which they acquire excitability characteristics crucial for development of presynaptic and postsynaptic connectivity. In contrast to earlier specification programs, little is known about the regulatory mechanisms that control neuronal maturation. The Pet-1 ETS (E26 transformation-specific) factor is continuously expressed in serotonin (5-HT) neurons and initially acts in postmitotic precursors to control acquisition of 5-HT transmitter identity. Using a combination of RNA sequencing, electrophysiology, and conditional targeting approaches, we determined gene expression patterns in maturing flow-sorted 5-HT neurons and the temporal requirements for Pet-1 in shaping these patterns for functional maturation of mouse 5-HT neurons. We report a profound disruption of postmitotic expression trajectories in Pet-1(-/-) neurons, which prevented postnatal maturation of 5-HT neuron passive and active intrinsic membrane properties, G-protein signaling, and synaptic responses to glutamatergic, lysophosphatidic, and adrenergic agonists. Unexpectedly, conditional targeting revealed a postnatal stage-specific switch in Pet-1 targets from 5-HT synthesis genes to transmitter receptor genes required for afferent modulation of 5-HT neuron excitability. Five-HT1a autoreceptor expression depended transiently on Pet-1, thus revealing an early postnatal sensitive period for control of 5-HT excitability genes. Chromatin immunoprecipitation followed by sequencing revealed that Pet-1 regulates 5-HT neuron maturation through direct gene activation and repression. Moreover, Pet-1 directly regulates the 5-HT neuron maturation factor Engrailed 1, which suggests Pet-1 orchestrates maturation through secondary postmitotic regulatory factors. The early postnatal switch in Pet-1 targets uncovers a distinct neonatal stage-specific function for Pet-1, during which it promotes maturation of 5-HT neuron excitability. SIGNIFICANCE STATEMENT: The regulatory mechanisms that control functional maturation of neurons are poorly understood. We show that in addition to inducing brain serotonin (5-HT) synthesis and reuptake, the Pet-1 ETS (E26 transformation-specific) factor subsequently globally coordinates postmitotic expression trajectories of genes necessary for maturation of 5-HT neuron excitability. Further, Pet-1 switches its transcriptional targets as 5-HT neurons mature from 5-HT synthesis genes to G-protein-coupled receptors, which are necessary for afferent synaptic modulation of 5-HT neuron excitability. Our findings uncover gene-specific switching of downstream targets as a previously unrecognized regulatory strategy through which continuously expressed transcription factors control acquisition of neuronal identity at different stages of development.

Using Online Active-Learning Techniques to Convey Time Compensated Sun Compass Orientation in the Eastern North American Monarch.

A common tool that animals use to navigate in a constant direction is known as "time compensated sun compass orientation." This is a process by which animals use the position of the sun along with information from their internal circadian clocks to determine and maintain a directional heading. Many circadian scientists and educators use this process as an example of how the internal circadian clock can directly influence animal behavior. However, many students have difficulty grasping this biological process due to its multivariable nature. We have created an online module that uses the principles of active learning to facilitate student comprehension of this process. Our module contains instructional videos, practice problems and an interactive diagram. We implemented the module in an undergraduate biological clocks class at Vanderbilt University, where its use significantly improved students' understanding of time compensated sun compass orientation as well as their ability to solve complex problems involving principles associated with this process.

Photoperiod programs dorsal raphe serotonergic neurons and affective behaviors.

The serotonergic raphe nuclei of the midbrain are principal centers from which serotonin neurons project to innervate cortical and sub-cortical structures. The dorsal raphe nuclei receive light input from the circadian visual system and indirect input from the biological clock nuclei. Dysregulation of serotonin neurotransmission is implicated in neurobehavioral disorders, such as depression and anxiety, and alterations in the serotonergic phenotype of raphe neurons have dramatic effects on affective behaviors in rodents. Here, we demonstrate that day length (photoperiod) during development induces enduring changes in mouse dorsal raphe serotonin neurons­programming their firing rate, responsiveness to noradrenergic stimulation, intrinsic electrical properties, serotonin and norepinephrine content in the midbrain, and depression/anxiety-related behavior in a melatonin receptor 1 (MT1)-dependent manner. Our results establish mechanisms by which seasonal photoperiods may dramatically and persistently alter the function of serotonin neurons.

Physical Interactions and Functional Relationships of Neuroligin 2 and Midbrain Serotonin Transporters.

The neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] modulates many key brain functions including those subserving sensation, emotion, reward, and cognition. Efficient clearance of 5-HT after release is achieved by the antidepressant-sensitive 5-HT transporter (SERT, SLC6A4). To identify novel SERT regulators, we pursued a proteomic analysis of mouse midbrain SERT complexes, evaluating findings in the context of prior studies that established a SERT-linked transcriptome. Remarkably, both efforts converged on a relationship of SERT with the synaptic adhesion protein neuroligin 2 (NLGN2), a post-synaptic partner for presynaptic neurexins, and a protein well-known to organize inhibitory GABAergic synapses. Western blots of midbrain reciprocal immunoprecipitations confirmed SERT/NLGN2 associations, and also extended to other NLGN2 associated proteins [e.g., α-neurexin (NRXN), gephyrin]. Midbrain SERT/NLGN2 interactions were found to be Ca(2+)-independent, supporting cis vs. trans-synaptic interactions, and were absent in hippocampal preparations, consistent with interactions arising in somatodendritic compartments. Dual color in situ hybridization confirmed co-expression of Tph2 and Nlgn2 mRNA in the dorsal raphe, with immunocytochemical studies confirming SERT:NLGN2 co-localization in raphe cell bodies but not axons. Consistent with correlative mRNA expression studies, loss of NLGN2 expression in Nlgn2 null mice produced significant reductions in midbrain and hippocampal SERT expression and function. Additionally, dorsal raphe 5-HT neurons from Nlgn2 null mice exhibit reduced excitability, a loss of GABAA receptor-mediated IPSCs, and increased 5-HT1A autoreceptor sensitivity. Finally, Nlgn2 null mice display significant changes in behaviors known to be responsive to SERT and/or 5-HT receptor manipulations. We discuss our findings in relation to the possible coordination of intrinsic and extrinsic regulation afforded by somatodendritic SERT:NLGN2 complexes.

Measuring circadian advantage in Major League Baseball: a 10-year retrospective study.

PURPOSE: The effect of travel on athletic performance has been investigated in previous studies. The purpose of this study was to investigate this effect on game outcome over 10 Major League Baseball (MLB) seasons. METHODS: Using the convention that for every time zone crossed, synchronization requires 1 d, teams were assigned a daily number indicating the number of days away from circadian resynchronization. With these values, wins and losses for all games could be analyzed based on circadian values. RESULTS: 19,079 of the 24,121 games (79.1%) were played between teams at an equal circadian time. The remaining 5,042 games consisted of teams playing at different circadian times. The team with the circadian advantage won 2,620 games (52.0%, P = .005), a winning percentage that exceeded chance but was a smaller effect than home field advantage (53.7%, P < .0001). When teams held a 1-h circadian advantage, winning percentage was 51.7% (1,903-1,781). Winning percentage with a 2-h advantage was 51.8% (620-578) but increased to 60.6% (97-63) with a 3-h advantage (3-h advantage > 2-hadvantage = 1-h advantage, P = .036). Direction of advantage showed teams traveling from Western time zones to Eastern time zones were more likely to win (winning percentage = .530) than teams traveling from Eastern time zones to Western time zones (winning percentage = .509) with a winning odds 1.14 (P = .027). CONCLUSION: These results suggest that in the same way home field advantage influences likelihood of success, so too does the magnitude and direction of circadian advantage. Teams with greater circadian advantage were more likely to win.