Injured adult neurons regress to an embryonic transcriptional growth state.

Grafts of spinal-cord-derived neural progenitor cells (NPCs) enable the robust regeneration of corticospinal axons and restore forelimb function after spinal cord injury1; however, the molecular mechanisms that underlie this regeneration are unknown. Here we perform translational profiling specifically of corticospinal tract (CST) motor neurons in mice, to identify their 'regenerative transcriptome' after spinal cord injury and NPC grafting. Notably, both injury alone and injury combined with NPC grafts elicit virtually identical early transcriptomic responses in host CST neurons. However, in mice with injury alone this regenerative transcriptome is downregulated after two weeks, whereas in NPC-grafted mice this transcriptome is sustained. The regenerative transcriptome represents a reversion to an embryonic transcriptional state of the CST neuron. The huntingtin gene (Htt) is a central hub in the regeneration transcriptome; deletion of Htt significantly attenuates regeneration, which shows that Htt has a key role in neural plasticity after injury.

Adult rat myelin enhances axonal outgrowth from neural stem cells.

Axon regeneration after spinal cord injury (SCI) is attenuated by growth inhibitory molecules associated with myelin. We report that rat myelin stimulated the growth of axons emerging from rat neural progenitor cells (NPCs) transplanted into sites of SCI in adult rat recipients. When plated on a myelin substrate, neurite outgrowth from rat NPCs and from human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) was enhanced threefold. In vivo, rat NPCs and human iPSC-derived NSCs extended greater numbers of axons through adult central nervous system white matter than through gray matter and preferentially associated with rat host myelin. Mechanistic investigations excluded Nogo receptor signaling as a mediator of stem cell-derived axon growth in response to myelin. Transcriptomic screens of rodent NPCs identified the cell adhesion molecule neuronal growth regulator 1 (Negr1) as one mediator of permissive axon-myelin interactions. The stimulatory effect of myelin-associated proteins on rodent NPCs was developmentally regulated and involved direct activation of the extracellular signal-regulated kinase (ERK). The stimulatory effects of myelin on NPC/NSC axon outgrowth should be investigated further and could potentially be exploited for neural repair after SCI.

Learning Neuroscience with Technology: A Scaffolded, Active Learning Approach.

Mobile applications (apps) for learning technical scientific content are becoming increasingly popular in educational settings. Neuroscience is often considered complex and challenging for most students to understand conceptually. iNeuron is a recently developed iOS app that teaches basic neuroscience in the context of a series of scaffolded challenges to create neural circuits and increase understanding of nervous system structure and function. In this study, four different ways to implement the app within a classroom setting were explored. The goal of the study was to determine the app's effectiveness under conditions closely approximating real-world use, and to evaluate whether collaborative play and student-driven navigational features contributed to its effectiveness. Students used the app either individually or in small groups, and used a version with either a fixed or variable learning sequence. Student performance on a pre- and post- neuroscience content assessment was analyzed and compared between students who used the app and a control group receiving standard instruction, and logged app data were analyzed. Significantly greater learning gains were found for all students who used the app compared to control. All four implementation modes were effective in producing student learning gains relative to controls, but did not differ in their effectiveness to one another. In addition, students demonstrated transfer of information learned in one context to another within the app. These results suggest that teacher-led neuroscience instruction can be effectively supported by a scaffolded, technology-based curriculum which can be implemented in multiple ways to enhance student learning.

Perceived Challenges in Primary Literature in a Master's Class: Effects of Experience and Instruction.

Primary literature offers rich opportunities to teach students how to "think like a scientist," but the challenges students face when they attempt to read research articles are not well understood. Here, we present an analysis of what master's students perceive as the most challenging aspects of engaging with primary literature. We examined 69 pairs of pre- and postcourse responses from students enrolled in a master's-level course that offered a structured analysis of primary literature. On the basis of these responses, we identified six categories of challenges. Before instruction, "techniques" and "experimental data" were the most frequently identified categories of challenges. The majority of difficulties students perceived in the primary literature corresponded to Bloom's lower-order cognitive skills. After instruction, "conclusions" were identified as the most difficult aspect of primary literature, and the frequency of challenges that corresponded to higher-order cognitive skills increased significantly among students who reported less experience with primary literature. These changes are consistent with a more competent perception of the primary literature, in which these students increasingly focus on challenges requiring critical thinking. Students' difficulties identified here can inform the design of instructional approaches aimed to teach students how to critically read scientific papers.

Critical Analysis of Primary Literature in a Master's-Level Class: Effects on Self-Efficacy and Science-Process Skills.

The ability to think analytically and creatively is crucial for success in the modern workforce, particularly for graduate students, who often aim to become physicians or researchers. Analysis of the primary literature provides an excellent opportunity to practice these skills. We describe a course that includes a structured analysis of four research papers from diverse fields of biology and group exercises in proposing experiments that would follow up on these papers. To facilitate a critical approach to primary literature, we included a paper with questionable data interpretation and two papers investigating the same biological question yet reaching opposite conclusions. We report a significant increase in students' self-efficacy in analyzing data from research papers, evaluating authors' conclusions, and designing experiments. Using our science-process skills test, we observe a statistically significant increase in students' ability to propose an experiment that matches the goal of investigation. We also detect gains in interpretation of controls and quantitative analysis of data. No statistically significant changes were observed in questions that tested the skills of interpretation, inference, and evaluation.