Identification of the cortical neurons that mediate antidepressant responses.

Our understanding of current treatments for depression, and the development of more specific therapies, is limited by the complexity of the circuits controlling mood and the distributed actions of antidepressants. Although the therapeutic efficacy of serotonin-specific reuptake inhibitors (SSRIs) is correlated with increases in cortical activity, the cell types crucial for their action remain unknown. Here we employ bacTRAP translational profiling to show that layer 5 corticostriatal pyramidal cells expressing p11 (S100a10) are strongly and specifically responsive to chronic antidepressant treatment. This response requires p11 and includes the specific induction of Htr4 expression. Cortex-specific deletion of p11 abolishes behavioral responses to SSRIs, but does not lead to increased depression-like behaviors. Our data identify corticostriatal projection neurons as critical for the response to antidepressants, and suggest that the regulation of serotonergic tone in this single cell type plays a pivotal role in antidepressant therapy.

Active learning narrows achievement gaps for underrepresented students in undergraduate science, technology, engineering, and math.

We tested the hypothesis that underrepresented students in active-learning classrooms experience narrower achievement gaps than underrepresented students in traditional lecturing classrooms, averaged across all science, technology, engineering, and mathematics (STEM) fields and courses. We conducted a comprehensive search for both published and unpublished studies that compared the performance of underrepresented students to their overrepresented classmates in active-learning and traditional-lecturing treatments. This search resulted in data on student examination scores from 15 studies (9,238 total students) and data on student failure rates from 26 studies (44,606 total students). Bayesian regression analyses showed that on average, active learning reduced achievement gaps in examination scores by 33% and narrowed gaps in passing rates by 45%. The reported proportion of time that students spend on in-class activities was important, as only classes that implemented high-intensity active learning narrowed achievement gaps. Sensitivity analyses showed that the conclusions are robust to sampling bias and other issues. To explain the extensive variation in efficacy observed among studies, we propose the heads-and-hearts hypothesis, which holds that meaningful reductions in achievement gaps only occur when course designs combine deliberate practice with inclusive teaching. Our results support calls to replace traditional lecturing with evidence-based, active-learning course designs across the STEM disciplines and suggest that innovations in instructional strategies can increase equity in higher education.

Co-teaching in Undergraduate STEM Education: A Lever for Pedagogical Change toward Evidence-Based Teaching?

Could co-teaching be a mechanism to support the adoption of evidence-based teaching strategies? Co-teaching has been proposed as a lever for fostering pedagogical change and has key attributes of a successful change strategy, but does research indicate co-teaching effectively shifts instructional practices? Based on our review of the emerging evidence, we wrote this essay for multiple audiences, including science, technology, engineering, and mathematics (STEM) instructors, education development professionals, leaders who oversee teaching, and researchers. We define co-teaching in the context of STEM higher education and summarize what is known about the pedagogical changes that co-teaching could support and the potential mechanisms behind these changes. We share recommendations based on the available evidence for those who need productive ideas right now. We also lay out a variety of future directions for research about co-teaching as a lever for pedagogical change. Achieving widespread and impactful pedagogical change is a monumental undertaking facing STEM higher education, and multiple approaches will be needed to meet this challenge. Co-teaching has potential to shift ways of thinking and pedagogical practices among undergraduate STEM faculty, but how co-teaching is enacted is likely crucial to its impact, as is the context in which it occurs.

A metagenomic study of primate insect diet diversity.

Descriptions of primate diets are generally based on either direct observation of foraging behavior, morphological classification of food remains from feces, or analysis of the stomach contents of deceased individuals. Some diet items (e.g. insect prey), however, are difficult to identify visually, and observation conditions often do not permit adequate quantitative sampling of feeding behavior. Moreover, the taxonomically informative morphology of some food species (e.g. swallowed seeds, insect exoskeletons) may be destroyed by the digestive process. Because of these limitations, we used a metagenomic approach to conduct a preliminary, "proof of concept" study of interspecific variation in the insect component of the diets of six sympatric New World monkeys known, based on observational field studies, to differ markedly in their feeding ecology. We used generalized arthropod polymerase chain reaction (PCR) primers and cloning to sequence mitochondrial DNA (mtDNA) sequences of the arthropod cytochrome b (CYT B) gene from fecal samples of wild woolly, titi, saki, capuchin, squirrel, and spider monkeys collected from a single sampling site in western Amazonia where these genera occur sympatrically. We then assigned preliminary taxonomic identifications to the sequences by basic local alignment search tool (BLAST) comparison to arthropod CYT B sequences present in GenBank. This study is the first to use molecular techniques to identify insect prey in primate diets. The results suggest that a metagenomic approach may prove valuable in augmenting and corroborating observational data and increasing the resolution of primate diet studies, although the lack of comparative reference sequences for many South American insects limits the approach at present. As such reference data become available for more animal and plant taxa, this approach also holds promise for studying additional components of primate diets.

Effects of Reading Interventions on Student Understanding of and Misconceptions about Antibiotic Resistance.

Students possess informal, intuitive ways of reasoning about the world, including biological phenomena. Although useful in some cases, intuitive reasoning can also lead to the development of scientifically inaccurate ideas that conflict with central concepts taught in formal biology education settings, including evolution. Using antibiotic resistance as an example of evolution, we developed a set of reading interventions and an assessment tool to examine the extent to which differences in instructional language affect undergraduate student misconceptions and intuitive reasoning. We find that readings that confront intuitive misconceptions can be more effective in reducing those misconceptions than factual explanations of antibiotic resistance that fail to confront misconceptions. Overall, our findings build upon investigations of intuitive reasoning in biology, examine possible instructional interventions, and raise questions about effective implementation of reading interventions in addressing persistent misconceptions about biology.

Unique molecular features and cellular responses differentiate two populations of motor cortical layer 5b neurons in a preclinical model of ALS.

Many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), lead to the selective degeneration of discrete cell types in the CNS despite the ubiquitous expression of many genes linked to disease. Therapeutic advancement depends on understanding the unique cellular adaptations that underlie pathology of vulnerable cells in the context of disease-causing mutations. Here, we employ bacTRAP molecular profiling to elucidate cell type-specific molecular responses of cortical upper motor neurons in a preclinical ALS model. Using two bacTRAP mouse lines that label distinct vulnerable or resilient projection neuron populations in motor cortex, we show that the regulation of oxidative phosphorylation (Oxphos) pathways is a common response in both cell types. However, differences in the baseline expression of genes involved in Stem and the handling of reactive oxygen species likely lead to the selective degeneration of the vulnerable cells. These results provide a framework to identify cell-type-specific processes in neurodegenerative disease.

Water Waves to Sound Waves: Using Zebrafish to Explore Hair Cell Biology.

Although perhaps best known for their use in developmental studies, over the last couple of decades, zebrafish have become increasingly popular model organisms for investigating auditory system function and disease. Like mammals, zebrafish possess inner ear mechanosensory hair cells required for hearing, as well as superficial hair cells of the lateral line sensory system, which mediate detection of directional water flow. Complementing mammalian studies, zebrafish have been used to gain significant insights into many facets of hair cell biology, including mechanotransduction and synaptic physiology as well as mechanisms of both hereditary and acquired hair cell dysfunction. Here, we provide an overview of this literature, highlighting some of the particular advantages of using zebrafish to investigate hearing and hearing loss.

Cumulative mitochondrial activity correlates with ototoxin susceptibility in zebrafish mechanosensory hair cells.

Mitochondria play a prominent role in mechanosensory hair cell damage and death. Although hair cells are thought to be energetically demanding cells, how mitochondria respond to these demands and how this might relate to cell death is largely unexplored. Using genetically encoded indicators, we found that mitochondrial calcium flux and oxidation are regulated by mechanotransduction and demonstrate that hair cell activity has both acute and long-term consequences on mitochondrial function. We tested whether variation in mitochondrial activity reflected differences in the vulnerability of hair cells to the toxic drug neomycin. We observed that susceptibility did not correspond to the acute level of mitochondrial activity but rather to the cumulative history of that activity.

Mitochondrial calcium uptake underlies ROS generation during aminoglycoside-induced hair cell death.

Exposure to aminoglycoside antibiotics can lead to the generation of toxic levels of reactive oxygen species (ROS) within mechanosensory hair cells of the inner ear that have been implicated in hearing and balance disorders. Better understanding of the origin of aminoglycoside-induced ROS could focus the development of therapies aimed at preventing this event. In this work, we used the zebrafish lateral line system to monitor the dynamic behavior of mitochondrial and cytoplasmic oxidation occurring within the same dying hair cell following exposure to aminoglycosides. The increased oxidation observed in both mitochondria and cytoplasm of dying hair cells was highly correlated with mitochondrial calcium uptake. Application of the mitochondrial uniporter inhibitor Ru360 reduced mitochondrial and cytoplasmic oxidation, suggesting that mitochondrial calcium drives ROS generation during aminoglycoside-induced hair cell death. Furthermore, targeting mitochondria with free radical scavengers conferred superior protection against aminoglycoside exposure compared with identical, untargeted scavengers. Our findings suggest that targeted therapies aimed at preventing mitochondrial oxidation have therapeutic potential to ameliorate the toxic effects of aminoglycoside exposure.

Large basolateral processes on type II hair cells are novel processing units in mammalian vestibular organs.

Sensory receptors in the vestibular system (hair cells) encode head movements and drive central motor reflexes that control gaze, body movements, and body orientation. In mammals, type I and II vestibular hair cells are defined by their shape, contacts with vestibular afferent nerves, and membrane conductance. Here we describe unique morphological features of type II vestibular hair cells in mature rodents (mice and gerbils) and bats. These features are cytoplasmic processes that extend laterally from the hair cell base and project under type I hair cells. Closer analysis of adult mouse utricles demonstrated that the basolateral processes of type II hair cells vary in shape, size, and branching, with the longest processes extending three to four hair cell widths. The hair cell basolateral processes synapse upon vestibular afferent nerves and receive inputs from vestibular efferent nerves. Furthermore, some basolateral processes make physical contacts with the processes of other type II hair cells, forming some sort of network among type II hair cells. Basolateral processes are rare in perinatal mice and do not attain their mature form until 3-6 weeks of age. These observations demonstrate that basolateral processes are significant signaling regions of type II vestibular hair cells and suggest that type II hair cells may directly communicate with each other, which has not been described in vertebrates.