Precise levels of nectin-3 are required for proper synapse formation in postnatal visual cortex
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RESEARCH ARTICLE
Open Access
Precise levels of nectin-3 are required for proper synapse formation in postnatal visual cortex Johanna Tomorsky1,2,3*, Philip R. L. Parker1,2, Chris Q. Doe1,2,4,5 and Cristopher M. Niell1,2*
Abstract 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. Keywords: Visual cortex, Nectin-3, Postnatal development, Eye opening, Synapse formation, Dendritic spine density, Layer 2/3
Background The development of mature brain circuits requires the selective formation, elimination, and strengthening of synaptic connections between neurons [1, 2]. This process requires the timed expression and spatial localization of proteins that are just beginning to be elucidated [3–5]. Many studies * Correspondence: [email protected]; [email protected] 1 Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA Full list of author information is available at the end of the article
indicate that cell-adhesion molecules are involved in the formation and strengthening of synapses, though much is unknown about their specific roles in the maturation of various brain circuits [6–11]. The number and strength of synapses found on visual cortical neurons, inferred from dendritic spine density and shape, depend on visual experience and developmental stage [1, 12–19]. During the postnatal development of visual cortex, neurons experience an early increase
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