A Discussion of Diversity and Inclusivity at the Institutional Level: The Need for a Strategic Plan.

A wider discussion is taking place nationally regarding how universities can make 'real' change in the old way of academic business. These changes include a hard look at the inclusive nature of the institutional environment as a whole. Lack of diversity is most noticeable within higher administrative levels of universities across the country. We have now reached a point where true reflection and assessment of inclusive practices on our campuses must be carried out so that we fully serve the needs of all of our students. In this breakout session participants will share best practices currently in place or strategic planning at your institutions, which not only promote diversity and inclusion in the classroom but describe strategies for institutional buy-in at all levels and provide examples of accountability measures that further promote diversity and inclusion at higher administrative levels.

Effects of binge ethanol exposure during first-trimester equivalent on corticothalamic neurons in Swiss Webster outbred mice.

Fetal alcohol spectrum disorders range in severity depending on the amount, timing, and frequency of alcohol exposure. Regardless of severity, sensorimotor defects are commonly reported. Sensorimotor information travels through three tracts of the internal capsule: thalamocortical axons, corticothalamic axons, and corticospinal axons. Here we describe the effects of binge ethanol exposure during the first-trimester equivalent on corticothalamic neurons using Swiss Webster mice. We injected pregnant mice with ethanol (2.9 g/kg, intraperitoneal, followed by 1.45 g/kg, intraperitoneal, 2 h later) on embryonic days (E) 11.5, 12.5, and 13.5. Our paradigm resulted in a mean maternal blood ethanol content of 294.8±15.4 mg/dl on E12.5 and 258.3±22.2 mg/dl on E13.5. Control dams were injected with an equivalent volume of PBS. Bromodeoxyuridine birthdating was carried out on E11.5 to label S-phase neurons. The days of injection were chosen because they are at the onset of neurogenesis and axon extension for corticothalamic, thalamocortical, and corticospinal neurons. Ethanol-exposed pups exhibited no differences compared with controls on day of birth in litter size, body weight, or brain weight. Corticothalamic neurons labeled with bromodeoxyuridine and T-box brain 1 were located in the deep layers of the cortex and did not differ in number in both groups. These results contrast several studies demonstrating alcohol-related differences in these parameters using chronic ethanol exposure paradigms and inbred mouse strains. Therefore, our findings highlight the importance of expanding the mouse strains used to model fetal alcohol spectrum disorder to enhance our understanding of its complex etiology.

Mutation of the BiP/GRP78 gene causes axon outgrowth and fasciculation defects in the thalamocortical connections of the mammalian forebrain.

Proper development of axonal connections is essential for brain function. A forward genetic screen for mice with defects in thalamocortical development previously isolated a mutant called baffled. Here we describe the axonal defects of baffled in further detail and identify a point mutation in the Hspa5 gene, encoding the endoplasmic reticulum chaperone BiP/GRP78. This hypomorphic mutation of BiP disrupts proper development of the thalamocortical axon projection and other forebrain axon tracts, as well as cortical lamination. In baffled mutant brains, a reduced number of thalamic axons innervate the cortex by the time of birth. Thalamocortical and corticothalamic axons are delayed, overfasciculated, and disorganized along their pathway through the ventral telencephalon. Furthermore, dissociated mutant neurons show reduced axon extension in vitro. Together, these findings demonstrate a sensitive requirement for the endoplasmic reticulum chaperone BiP/GRP78 during axon outgrowth and pathfinding in the developing mammalian brain.

A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct emx2 mutant phenotype.

BACKGROUND: The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood. RESULTS: To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-tau-lacZ reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as reeler. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the Emx2 gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development. CONCLUSIONS: These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the Emx2 mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.

A pharmacological activator of AMP-activated protein kinase (AMPK) induces astrocyte stellation.

AMP-activated protein kinase (AMPK) represents a key energy-sensing molecule in many cell types. Because astrocytes are key mediators of metabolic signaling in the brain, we have initiated studies on the expression and activation of AMPK in these cells. Treatment of cultured rat cortical astrocytes with a pharmacological AMPK activator, AICA-riboside (AICAR) resulted in a time- and concentration-dependent increase in phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a direct substrate. AICAR treatment also induced a transition from epithelioid to stellate morphology in a time- and concentration-dependent manner. As stellation is indicative of actin cytoskeletal reorganization, the formation of stress fibers and focal adhesions in response to AICAR was assessed. AICAR-induced stellation correlated with F-actin disassembly and focal adhesion dispersal. Furthermore, transient transfection of an activated RhoA construct prevented AICAR-induced stellation, indicating a mechanism upstream of RhoA. Use of pharmacological inhibitor compound C prevented AICAR-induced stellation demonstrating necessity of AMPK activity for the response. Our findings suggest that AMPK mediates morphological alterations of astrocytes in response to energy depletion.