The rod synapse in aging wildtype and Dscaml1 mutant mice.

The retina is an intricately organized neural tissue built on cone and rod pathways for color and night vision. Genetic mutations that disrupt the proper function of the rod circuit contribute to blinding diseases including retinitis pigmentosa and congenital stationary night blindness (CSNB). Down Syndrome cell adhesion molecule like 1 (Dscaml1) is expressed by rods, rod bipolar cells (RBCs), and sub-populations of amacrine cells, and has been linked to a middle age onset of CSNB in humans. However, how Dscaml1 contributes to this visual deficit remains unexplored. Here, we probed Dscaml1's role in the maintenance of the rod-to-RBC synapse using a loss of function mouse model. We used immunohistochemistry to investigate the anatomical formation and maintenance of the rod-to-RBC synapse in the young, adult, and aging retina. We generated 3D reconstructions, using serial electron micrographs, of rod spherules and RBCs to measure the number of invaginating neurites, RBC dendritic tip number, and RBC mitochondrial morphology. We find that while rod-to-RBC synapses form and are maintained, similar to wildtype, that there is an increase in the number of invaginating neurites in rod spherules, a reduction in RBC dendritic tips, and reduced mitochondrial volume and complexity in the Dscaml1 mutant retina compared to controls. We also observed precocious sprouting of RBC dendrites into the outer nuclear layer (ONL) of the Dscaml1 mutant retina compared to controls. These results contribute to our knowledge of Dscaml1's role in rod circuit development and maintenance and give additional insight into possible genetic therapy targets for blinding diseases and disorders like CSNB.

Student remote and distance research in neuroanatomy: Mapping Dscaml1 expression with a LacZ gene trap in mouse brain.

Undergraduate student engagement in research increases retention and degree completion, especially for students who are underrepresented in science. Several approaches have been adopted to increase research opportunities including curriculum based undergraduate research opportunities (CUREs), in which research is embedded into course content. Here we report on efforts to tackle a different challenge: providing research opportunities to students engaged in remote learning or who are learning at satellite campuses or community colleges with limited research infrastructure. In our project we engaged students learning remotely or at regional centers to map gene expression in the mouse brain. In this project we mapped expression of the Down syndrome cell adhesion molecule like 1 (Dscaml1) gene in mouse brain using a LacZ expression reporter line. Identifying where Dscaml1 is expressed in the brain is an important next step in determining if its roles in development and function in the retina are conserved in the rest of the brain. Students working remotely reconstruct brain montages and annotated Dscaml1 expression in the brain of mice carrying one or two copies of the gene trap. We built on these findings by further characterizing Dscaml1 expression in inhibitory neurons of the visual pathway. These results build on and extend previous findings and demonstrate the utility of including distance learners in an active research group for both the student learners and the research team. We conclude with best practices we have developed based on this and other distance learner focused projects.