The generation of the most abundant neurons of the cerebellum, the granule cells, relies on a balance between clonal expansion and apoptosis during the first 10 days after birth in the external germinal layer (EGL). The amino acid glutamate controls such critical phases of cell development in other systems through specific receptors such as metabotropic glutamate receptor 5 (mGlu5R). However, the function of mGlu5Rs on the proliferation and survival of granule cell precursors (GCPs) remains elusive. We found mGlu5R mRNA transcripts in EGL using RT-PCR and observed mGlu5R-mediated Ca2+ responses in GCPs in acute slices as early as postnatal day (P) 2–3. Using in vivo injections of the selective non-competitive mGlu5R antagonist 2-Methyl-6-(phenylethynyl)pyridine (MPEP) in P7–9 mice, we found a 20% increase in the number of proliferative GCPs labeled at P7 with the S-phase marker bromodeoxyuridine (BrdU), but no increase in cell proliferation examined 2 hours following a BrdU injection. Furthermore, similar treatments led to a significant 70% decrease in the number of apoptotic GCPs in the EGL as determined by TUNEL staining. In contrast, in vivo treatment with the mGlu5R agonist (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG) resulted in a ~60% increase in the number of TUNEL-labeled GCPs compared to control. These findings identify a unique role for glutamate acting at mGlu5Rs as a functional switch regulating GCP survival in the EGL, thus controlling the total number of cerebellar granule cells produced.

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The “replication crisis” is a methodological problem in which many scientific research findings have been difficult or impossible to replicate. Because the reproducibility of empirical results is an essential aspect of the scientific method, such failures endanger the credibility of theories based on them and possibly significant portions of scientific knowledge. An instance of the replication crisis, analytic replication, pertains to reproducing published results through computational reanalysis of the authors’ original data. However, direct replications are costly, time-consuming, and unrewarded in today’s publishing standards. We propose that bioinformatics and computational biology students replicate recent discoveries as part of their curriculum. Considering the above, we performed a pilot study in one of the graduate-level courses we developed and taught at our University. The course is entitled Intro to R Programming and is meant for students in our Master’s and PhD programs who have little to no programming skills. As the course emphasized real-world data analysis, we thought it would be an appropriate setting to carry out this study. The primary objective was to expose the students to real biological data analysis problems. These include locating and downloading the needed datasets, understanding any underlying conventions and annotations, understanding the analytical methods, and regenerating multiple graphs from their assigned article. The secondary goal was to determine whether the assigned articles contained sufficient information for a graduate-level student to replicate its figures. Overall, the students successfully reproduced 39% of the figures. The main obstacles were the need for more advanced programming skills and the incomplete documentation of the applied methods. Students were engaged, enthusiastic, and focused throughout the semester. We believe that this teaching approach will allow students to make fundamental scientific contributions under appropriate supervision. It will teach them about the scientific process, the importance of reporting standards, and the importance of openness.

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As social animals, our health depends in part on interactions with other human beings. Yet millions suffer from chronic social isolation, including those in nursing/assisted living facilities and people experiencing chronic loneliness. Perhaps the most egregious form of chronic isolation is seen in criminal justice system, where approximately 80,000 people are housed, on any one day, in solitary confinement. In this study, we developed a model of isolation that starts in adulthood. Mice (C57BL/6J) were born and raised in an enriched environment until 4 months of age and then either maintained in that environment or moved to social isolation for 1 or 3 months. We then examined neuronal structure, catecholamine and brain derived neurotrophic factor (BDNF) levels, and CNS-mediated behaviors, comparing social isolation to enriched environment controls. We found there were significant changes in neuronal volume, dendritic length, neuronal complexity, and spine density that were dependent on brain region, sex, and duration of the isolation. Isolation altered dopamine in the striatum and serotonin levels in the forebrain in a sex-dependent manner, and also reduced levels of BDNF in the motor cortex and hippocampus of male but not female mice. To determine if SI altered a behavior, we tested mice in the open-field (general activity), the resident intruder paradigm (aggression), the tail suspension test (depression), and the Barnes maze (spatial memory). Adult male mice isolated for 1 month exhibited increased locomotor activity, aggression, and enhanced aspects of spatial memory, most of which remained after 3 months of isolation. After 3 months of isolation, mice also exhibited depressive behaviors. Similar (but not exact) results were seen in female mice, with the exception that the females did not show increased aggression. These studies show that isolation enforced in adulthood has significant impact on brain structure, neurochemistry, and behavior