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dc.contributor.advisorElly Nedivi.en_US
dc.contributor.authorVilla, Katherine L. (Katherine Leigh)en_US
dc.contributor.otherMassachusetts Institute of Technology. Department of Biology.en_US
dc.date.accessioned2016-06-20T17:18:55Z
dc.date.available2016-06-20T17:18:55Z
dc.date.issued2016en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/103167
dc.descriptionThesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016.en_US
dc.descriptionThis electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.en_US
dc.descriptionCataloged from student-submitted PDF version of thesis. "February 2016."en_US
dc.descriptionIncludes bibliographical references (pages 113-123).en_US
dc.description.abstractStructural plasticity, the rewiring of synaptic connections, occurs not only during development, but is prevalent in the adult brain and likely represents the physical correlate of learning and memory. Removal or addition of excitatory and inhibitory synaptic inputs onto a neuron can affect their relative influence on excitation in specific dendritic segments, and ultimately regulate neuronal firing. However, the structural dynamics of excitatory and inhibitory synapses in vivo, and their relation to each other, is not well understood. To gain insight into synaptic remodeling in the adult brain in vivo, we used dual- and triple- color two-photon imaging to track the dynamics of all inhibitory and excitatory synapses onto a given neuron in the cerebral cortex at different timescales. By studying synaptic changes over 4-day or 24-hour intervals we were able to determine that inhibitory synapses are remarkably dynamic in vivo. We found that Inhibitory synapses occur not only on the dendritic shaft, but also a significant fraction is present on dendritic spines, alongside an excitatory synapse. Inhibitory synapses on these dually innervated spines are remarkably dynamic and in stark contrast to the stability of excitatory synapses on the same spines. Many of the inhibitory synapses on dendritic spines repeatedly disappear and reappear in the same location. These reversible structural dynamics indicate a fundamentally new role for inhibitory synaptic remodeling - flexible, input-specific modulation of stable excitatory connections. To determine whether synapse dynamics are regulated by experience-dependent plasticity, we performed monocular deprivation, finding that an ocular dominance shift reduces inhibitory synaptic lifetime and increases recurrence. To investigate the molecular mechanism of rapid inhibitory synapse appearance and removal, I am currently testing molecular interventions that influence the clustering of gephyrin, a scaffolding molecule that anchors inhibitory receptors at postsynaptic sites.en_US
dc.description.statementofresponsibilityby Katherine L. Villa.en_US
dc.format.extent123 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsM.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectBiology.en_US
dc.titleInhibitory synapses are repeatedly assembled and removed at persistent sites in vivoen_US
dc.typeThesisen_US
dc.description.degreePh. D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biology.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biology
dc.identifier.oclc951676646en_US


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