Assessment of Mapping the Brain, a Novel Research and Neurotechnology Based Approach for the Modern Neuroscience Classroom

Abstract

Neuroscience research is changing at an incredible pace due to technological innovation and recent national and global initiatives such as the BRAIN initiative. Given the wealth of data supporting the value of course-based undergraduate research experiences (CUREs) for students, we developed and assessed a neurotechnology CURE, Mapping the Brain. The goal of the course is to immerse undergraduate and graduate students in research and to explore technological advances in neuroscience. In the laboratory portion of the course, students pursued a hypothesis-driven, collaborative National Institutes of Health (NIH) research project. Using chemogenetic technology (Designer Receptors Exclusively Activated by Designer Drugs-DREADDs) and a recombinase-based intersectional genetic strategy, students mapped norepinephrine neurons, and their projections and explored the effects of activating these neurons in vivo. In lecture, students compared traditional and cutting-edge neuroscience methodologies, analyzed primary literature, designed hypothesis-based experiments, and discussed technological limitations of studying the brain. Over two consecutive years in the Program at North Carolina State University, we assessed student learning and perceptions of learning based on Society for Neuroscience's (SfN) core concepts and essential principles of neuroscience. Using analysis of student assignments and pre/post content and perception-based course surveys, we also assessed whether the course improved student research article analysis and neurotechnology assessment. Our analyses reveal new insights and pedagogical approaches for engaging students in research and improving their critical analysis of research articles and neurotechnologies. Our data also show that our multifaceted approach increased student confidence and promoted a data focused mentality when tackling research literature. Through the integration of authentic research and a neurotechnology focus, Mapping the Brain provides a unique model as a modern neuroscience laboratory course.

Keywords: BRAIN Initiative; CURE (course based undergraduate research experience); FIGURE FACTS; collaborative research; graduate education; laboratory education; primary literature; technology.

Figure 1

Laboratory and lesson structure of Mapping the Brain. Weekly 5-hour laboratory sessions focused on a collaborative NIH research project (green). Students worked with brain tissue and behavioral data from transgenic mice to map a subset of norepinephrine neurons, analyze their projections, and explore the effects of activating these neurons in vivo. Students performed fluorescent and 3,3-diaminobenzidine (DAB) horseradish peroxidase (HRP) immunohistochemistry experiments and analyzed behavioral data collected from their animals in the light/dark box, elevated plus maze and open field paradigms. Two additional laboratory sessions provided hands on review of fundamental neuronal excitability principals utilizing Spiker boxes from Backyard Brains® and student presentations of team research design projects (blue weeks 2, 8). Weekly 110 min class sessions focused on a variety of neuroscience topics and technologies (blue arrows-lesson topics; grey box-neurotechnologies discussed). Three journal club sessions (grey ovals) enabled students to explore four research papers and their associated methodology.

Figure 2

Examples of student data from Mapping the Brain. Students performed fluorescent immunohistochemistry to assess if the new intersectional genetic approach worked and resulted in GFP (green) and hM3Dq-mCherry (violet) expression in the expected norepinephrine subgroups (top left). Students also searched their 40μm sections across the brain for ectopic GFP and hM3Dq-mCherry expression. Projections from the non-En1 NE subpopulation (GFP expressing) were also assessed using both fluorescent and DAB anti-GFP immunostaining (top right). Students identified known targets of NE projections (bed nucleus of the stria terminalis-BNST, basolateral amygdala posterior part-BLP, insular cortex-Ins Ctx, and paraventricular hypothalamus-PVN). (Middle Panel) Sample student analysis of behavioral data from the DREADD mice and their littermate controls (n=18–20). DREADD (left bars) and control mice (right bars) were treated with vehicle (blue) or CNO (grey) in the open field (left), light-dark box (middle) or elevated plus maze (right). Data are mean ± s.e.m. (*p <.05; unpaired t-test). Some student groups also performed an ANOVA. (Bottom Panel) Students assessed the efficacy of CNO in activating mCherry-DREADD En1-NE neurons using immunohistochemistry staining for c-fos relative to vehicle (VEH) treated DREADD mice (left two panels). Students also used c-fos to map neuronal activation patterns in response to En1-NE neuron stimulation with CNO compared to vehicle (VEH) treated DREADD mice. Students identified several areas with enhanced activation in CNO-treated compared to vehicle treated animals, an example in the periaqueductal gray (PAG) region is shown (right two panels).

Figure 3

Student achievement and perceptions of gains related to course learning outcomes (A) Intellectual and technical course learning outcomes (LO). (B) Analysis of student assignments to determine if students achieve the LOs. Student achievement of intellectual LOs was assessed based on the percent correct of related questions in the cumulative final exam (left bars). Student achievement of technical LOs was assessed based on research report analysis (middle bars). Student achievement of LO-9 and LO-10 from the cumulative final exam (striped bars) or research design project (checkered bars). A one-way ANOVA followed by a Tukey’s HSD test was used to compare levels of student achievement across outcomes. Student scores were only compared for outcomes assessed with the same assignment(s) (****p<.0001). (C) Pre- and post-course student perception of their ability to evaluate the limitations and potential of modern neuroscience tools (Wilcoxon*** p < .001) and analyze and interpret data from primary research articles that employ novel methodology (Wilcoxon **p < .01). (D) Post course, students indicated their perception of the impact of the course on their ability to do each LO. For each LO, students answered the question “By participating in this course, I gained the ability to…” using a Likert scale (strongly agree, agree, neither agree nor disagree, disagree, or strongly disagree). The percent of students is reported, and the color key shown in A indicates the LO in the bar graph. Strongly disagree is not shown because it was not selected by students for any LO.

Figure 4

Impact of Mapping the Brain on student stress, frustration and primary focus while reading research articles. (A) Pre- and post-course students selected their primary focus while reading a research article (one-tailed McNemar chi-square *p<.05). (B) Pre- and post-course students answered the questions “Reading primary research articles causes me to feel stressed (bottom bar), or frustrated (top bars) using a Likert scale, (Wilcoxon ps > .05).

Figure 5

Student perception of the SfN’s essential principles and core concepts of neuroscience. Students answered questions related to the essential principles and core concepts on a Likert scale (strongly agree, agree, neither agree nor disagree, disagree, or strongly disagree) with the exception of a question on neuronal communication. See Appendix 6 for the list of questions. The percent of students who strongly agree/agree is graphed pre-course (blue bars) and post-course (grey bars). Wilcoxon signed-rank tests to detect significant changes in frequencies of strongly agree/agree responses pre- and post-course were all non-significant (ps > .05).