Synaptic plasticity and morphogenesis in the developing postnatal cerebral cortex Public Deposited

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  • March 21, 2019
Creator
  • Powell, Jacqueline de Marchena
    • Affiliation: School of Medicine, UNC Neuroscience Center, Neuroscience Curriculum
Abstract
  • Learning how neurons interact, to create functional circuits, is crucial for understanding the basis of cognition and for shedding insight into the underpinnings of neurological disorders. This work will describe how changes in (1) postsynaptic N-methyl D-aspartate receptor (NMDAR) subunit composition and (2) dendritic spine morphology, influence synaptic transmission and synaptic plasticity in the developing cerebral cortex. Synaptic NMDARs undergo a dramatic activity-dependent change in subunit composition, going from being primarily NR2B-containing, to being increasingly NR2A-containing. Interestingly, this change in synaptic subunit composition correlates with developmental changes in the properties of synaptic plasticity. Using pharmacology, I have elucidated how NR2A- and NR2B-type NMDARs contribute to synaptic plasticity at distinct developmental time points. Using this approach, I demonstrate that the degree of NMDAR activation required for the induction of long term potentiation (LTP) increases with age. This work also focuses on the role of slit-robo GTPase activating protein 2 (srGAP2) on shaping the morphology of postsynaptic specializations, called dendritic spines. While the significance of dendritic spines is highly contentious, it has been shown that they play an important role in modulating the efficacy of glutamatergic synapses. This work demonstrates that srGAP2 is expressed at the synapse and that it has the ability to induce an elongation of dendritic spine shape, through the synergistic action of both its FBAR and RhoGAP domains. From a physiological perspective, srGAP2 also influences synaptic transmission, by altering the shape and the complement of receptors at the postsynaptic membrane. As a whole, this doctoral work highlights the importance of changes in postsynaptic receptor composition and dendritic spine morphology, in shaping neural circuitry.
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  • In Copyright
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  • "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Curriculum in Neurobiology."
Advisor
  • Polleux, Franck
  • Philpot, Benjamin
Degree granting institution
  • University of North Carolina at Chapel Hill
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Place of publication
  • Chapel Hill, NC
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  • Open access
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