Mechanisms of dendritic tiling - dendrites have diverse morphologies that are important for the neuron to properly process synaptic information

The $258,342 Project Grant from the National Institutes of Health's National Institute of Neurological Disorders and Stroke will support research into the mechanisms of dendritic tiling at Stanford University. Specifically, the grant will fund two specific aims: first, to test the hypothesis that activity-dependent mechanisms result in tiling of dendrites in C. elegans using live imaging of neighboring neurons labeled with distinct fluorescent reporters; and second, to assess the impact of extracellular ligands on downstream actin regulation necessary for tiling using genetic approaches. Insights gained from this research could yield understanding of how dendrites from adjacent neurons avoid one another during neural circuit assembly, as well as novel mechanisms regulating dynamic dendritic growth and retraction. The work is aligned with the NIH NINDS Extramural Research Programs in the Neurosciences and Neurological Disorders program's goal of supporting basic and clinical neuroscience research. The period of performance for this $258k award is from March 15, 2021 through August 14, 2022.

The spatial patterning of a neuron's dendritic arbor with respect to that of its neighbor is particularly relevant in sensory systems where stimulus detection must be efficient for downstream processing. In a phenomenon called dendritic tiling, neurons from a functional class that encode the same stimuli segregate into distinct mosaic patterns so that their dendrites rarely overlap with one another. Such dendritic tiling allows for spatial acuity by the nonredundant coverage of a receptive field. Specific aim 1 will test the hypothesis that activity-dependent mechanisms result in tiling of dendrites in the nematode c. Elegans using live imaging of neighboring neurons labeled with distinct fluorescent reporters. In specific aim 2, genetic approaches will be utilized to assess the impact of extracellular ligands on downstream actin regulation necessary for tiling. This proposal will yield insights into the cell biology of how dendrites from adjacent neurons avoid one another, as well as the novel mechanisms that regulate dynamic growth and retraction of dendrites during neural circuit assembly. Because dendritic pathologies have been observed in human patients with intellectual disorders, the proposed studies will also have applications that can contribute to potential therapies and preventative measures of neurological diseases.