Associate Professor, Department of Biology
Ph.D. Stanford University
B.S. Stanford Univeristy
Research Interests: Function and development of neural circuits for visual processing
Overview: How do we make sense of the visual world around us? Our brain takes a pattern of photons hitting the retina and continually creates a coherent representation of what we see – detecting objects and landmarks rather than just perceiving an array of pixels. This image processing allows us to perform a range of visual tasks, such as recognizing a friend’s face, finding your way to the grocery store, and catching a frisbee. However, how these computational feats are achieved by the neural circuitry of the visual system is largely unknown. Furthermore, this circuitry is wired up by a range of cellular processes, such as arbor growth, synapse formation, and activity-dependent plasticity, and thus these developmental mechanisms effectively determine how we see the world.
Our research is focused on understanding how neural circuits perform the image processing that allows us to perform complex visual behaviors, and how these circuits are assembled during development. We use in vivo recording techniques, including high-density extracellular recording and two-photon imaging, along with molecular genetic tools to dissect neural circuits, such as cell-type specific markers, optogenetic activation and inactivation, tracing of neural pathways, and in vivo imaging of dendritic and synaptic structure. We have also implemented behavioral tasks for mice so we can perform quantitative pyschophysics to measure the animal’s perception, and we use theoretical models to understand general computational principles being instantiated by a neural circuit.
Precise levels of nectin-3 are required for proper synapse formation in postnatal visual cortex.
Neural Dev. 2020 Nov 07;15(1):13
Authors: Tomorsky J, Parker PRL, Doe CQ, Niell CM
BACKGROUND: Developing cortical neurons express a tightly choreographed sequence of cytoskeletal and transmembrane proteins to form and strengthen specific synaptic connections during circuit formation. Nectin-3 is a cell-adhesion molecule with previously described roles in synapse formation and maintenance. This protein and its binding partner, nectin-1, are selectively expressed in upper-layer neurons of mouse visual cortex, but their role in the development of cortical circuits is unknown.
METHODS: Here we block nectin-3 expression (via shRNA) or overexpress nectin-3 in developing layer 2/3 visual cortical neurons using in utero electroporation. We then assay dendritic spine densities at three developmental time points: eye opening (postnatal day (P)14), one week following eye opening after a period of heightened synaptogenesis (P21), and at the close of the critical period for ocular dominance plasticity (P35).
RESULTS: Knockdown of nectin-3 beginning at E15.5 or ~ P19 increased dendritic spine densities at P21 or P35, respectively. Conversely, overexpressing full length nectin-3 at E15.5 decreased dendritic spine densities when all ages were considered together. The effects of nectin-3 knockdown and overexpression on dendritic spine densities were most significant on proximal secondary apical dendrites. Interestingly, an even greater decrease in dendritic spine densities, particularly on basal dendrites at P21, was observed when we overexpressed nectin-3 lacking its afadin binding domain.
CONCLUSION: These data collectively suggest that the proper levels and functioning of nectin-3 facilitate normal synapse formation after eye opening on apical and basal dendrites in layer 2/3 of visual cortex.
PMID: 33160402 [PubMed - in process]