{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/105027"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/105027","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Molecular mechanisms of synaptic plasticity","abstract":"Synaptic plasticity serves as a central molecular mechanism underlying learning and memory formation in the brain. An increase in intracellular calcium concentrations triggered by neuronal activity induces synaptic plasticity, and calmodulin is a key protein that detects the elevated calcium levels and propagates downstream signaling. Neurogranin is a neuron-specific protein that binds to calmodulin and regulates the availability of calmodulin in the postsynaptic compartments of excitatory neurons. Dysregulation of neurogranin has been reported to cause altered synaptic plasticity as well as impairment in hippocampus-dependent learning, and is also associated with the higher risk of developing neurodegenerative and psychiatric diseases. Therefore, it is critical to understand how neurogranin regulates the induction of synaptic plasticity in the brain at the molecular level. The focus of this thesis is to examine how the changes in neurogranin expression levels contribute to the induction of synaptic plasticity in the hippocampus with a spike-timing-dependent plasticity paradigm and to understand the underlying molecular mechanisms. Using lentivirus-mediated manipulations of neurogranin levels in hippocampal CAl neurons, we found that increasing neurogranin levels in CAI neurons prolongs the timing window for spike-timing-dependent long-term potentiation (LTP), whereas acute knockdown of neurogranin inhibits the expression of LTP via regulating PP2B activity. We have also found that neurogranin interferes with calcium-dependent inactivation of neuronal L-type calcium channels and allows a sustained influx of calcium during the membrane depolarization in hippocampal neurons. Our results indicate that dynamic changes in neurogranin levels play a crucial role in setting the threshold for inducing LTP in spike-timing-dependent plasticity in the hippocampus.","abstract_html":"Synaptic plasticity serves as a central molecular mechanism underlying learning and memory formation in the brain. An increase in intracellular calcium concentrations triggered by neuronal activity induces synaptic plasticity, and calmodulin is a key protein that detects the elevated calcium levels and propagates downstream signaling. Neurogranin is a neuron-specific protein that binds to calmodulin and regulates the availability of calmodulin in the postsynaptic compartments of excitatory neurons. Dysregulation of neurogranin has been reported to cause altered synaptic plasticity as well as impairment in hippocampus-dependent learning, and is also associated with the higher risk of developing neurodegenerative and psychiatric diseases. Therefore, it is critical to understand how neurogranin regulates the induction of synaptic plasticity in the brain at the molecular level. The focus of this thesis is to examine how the changes in neurogranin expression levels contribute to the induction of synaptic plasticity in the hippocampus with a spike-timing-dependent plasticity paradigm and to understand the underlying molecular mechanisms. Using lentivirus-mediated manipulations of neurogranin levels in hippocampal CAl neurons, we found that increasing neurogranin levels in CAI neurons prolongs the timing window for spike-timing-dependent long-term potentiation (LTP), whereas acute knockdown of neurogranin inhibits the expression of LTP via regulating PP2B activity. We have also found that neurogranin interferes with calcium-dependent inactivation of neuronal L-type calcium channels and allows a sustained influx of calcium during the membrane depolarization in hippocampal neurons. Our results indicate that dynamic changes in neurogranin levels play a crucial role in setting the threshold for inducing LTP in spike-timing-dependent plasticity in the hippocampus.","abstract_has_math":false,"creators":["Hwang, Hongik"],"institution":"Massachusetts Institute of Technology","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. Department of Chemistry.","school":null,"contributors":[],"advisors":["Weifeng Xu."],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016","date_published":"2016","updated_at":"2026-07-22T22:22:20Z","subjects":["Chemistry."],"languages":["eng"],"rights":["M.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."],"rights_urls":["http://dspace.mit.edu/handle/1721.1/7582"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1721.1/105027","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Weifeng Xu."]},{"key":"dc:contributor.department","label":"Department","values":["Massachusetts Institute of Technology. Department of Chemistry."]},{"key":"dc:contributor.other","label":"Dc Contributor Other","values":["Massachusetts Institute of Technology. Department of Chemistry."]},{"key":"dc:creator","label":"Author","values":["Hwang, Hongik"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2016-10-25T19:50:07Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2016-10-25T19:50:07Z"]},{"key":"dc:date.issued","label":"Date","values":["2016"]},{"key":"dc:publisher","label":"Institution","values":["Massachusetts Institute of Technology"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry."]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["M.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."]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://dspace.mit.edu/handle/1721.1/7582"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1721.1/105027"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Thesis: Ph. D. in Biological Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2016.","Cataloged from PDF version of thesis. Vita.","Includes bibliographical references."]},{"key":"dc:description.abstract","label":"Abstract","values":["Synaptic plasticity serves as a central molecular mechanism underlying learning and memory formation in the brain. An increase in intracellular calcium concentrations triggered by neuronal activity induces synaptic plasticity, and calmodulin is a key protein that detects the elevated calcium levels and propagates downstream signaling. Neurogranin is a neuron-specific protein that binds to calmodulin and regulates the availability of calmodulin in the postsynaptic compartments of excitatory neurons. Dysregulation of neurogranin has been reported to cause altered synaptic plasticity as well as impairment in hippocampus-dependent learning, and is also associated with the higher risk of developing neurodegenerative and psychiatric diseases. Therefore, it is critical to understand how neurogranin regulates the induction of synaptic plasticity in the brain at the molecular level. The focus of this thesis is to examine how the changes in neurogranin expression levels contribute to the induction of synaptic plasticity in the hippocampus with a spike-timing-dependent plasticity paradigm and to understand the underlying molecular mechanisms. Using lentivirus-mediated manipulations of neurogranin levels in hippocampal CAl neurons, we found that increasing neurogranin levels in CAI neurons prolongs the timing window for spike-timing-dependent long-term potentiation (LTP), whereas acute knockdown of neurogranin inhibits the expression of LTP via regulating PP2B activity. We have also found that neurogranin interferes with calcium-dependent inactivation of neuronal L-type calcium channels and allows a sustained influx of calcium during the membrane depolarization in hippocampal neurons. Our results indicate that dynamic changes in neurogranin levels play a crucial role in setting the threshold for inducing LTP in spike-timing-dependent plasticity in the hippocampus."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph. D. in Biological Chemistry"]},{"key":"dc:title","label":"Title","values":["Molecular mechanisms of synaptic plasticity"]}]}],"canonical_facts":{"dc:contributor.advisor":["Weifeng Xu."],"dc:contributor.department":["Massachusetts Institute of Technology. Department of Chemistry."],"dc:contributor.other":["Massachusetts Institute of Technology. Department of Chemistry."],"dc:creator":["Hwang, Hongik"],"dc:date.accessioned":["2016-10-25T19:50:07Z"],"dc:date.available":["2016-10-25T19:50:07Z"],"dc:date.issued":["2016"],"dc:description":["Thesis: Ph. D. in Biological Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2016.","Cataloged from PDF version of thesis. Vita.","Includes bibliographical references."],"dc:description.abstract":["Synaptic plasticity serves as a central molecular mechanism underlying learning and memory formation in the brain. An increase in intracellular calcium concentrations triggered by neuronal activity induces synaptic plasticity, and calmodulin is a key protein that detects the elevated calcium levels and propagates downstream signaling. Neurogranin is a neuron-specific protein that binds to calmodulin and regulates the availability of calmodulin in the postsynaptic compartments of excitatory neurons. Dysregulation of neurogranin has been reported to cause altered synaptic plasticity as well as impairment in hippocampus-dependent learning, and is also associated with the higher risk of developing neurodegenerative and psychiatric diseases. Therefore, it is critical to understand how neurogranin regulates the induction of synaptic plasticity in the brain at the molecular level. The focus of this thesis is to examine how the changes in neurogranin expression levels contribute to the induction of synaptic plasticity in the hippocampus with a spike-timing-dependent plasticity paradigm and to understand the underlying molecular mechanisms. Using lentivirus-mediated manipulations of neurogranin levels in hippocampal CAl neurons, we found that increasing neurogranin levels in CAI neurons prolongs the timing window for spike-timing-dependent long-term potentiation (LTP), whereas acute knockdown of neurogranin inhibits the expression of LTP via regulating PP2B activity. We have also found that neurogranin interferes with calcium-dependent inactivation of neuronal L-type calcium channels and allows a sustained influx of calcium during the membrane depolarization in hippocampal neurons. Our results indicate that dynamic changes in neurogranin levels play a crucial role in setting the threshold for inducing LTP in spike-timing-dependent plasticity in the hippocampus."],"dc:description.degree":["Ph. D. in Biological Chemistry"],"dc:identifier.uri":["http://hdl.handle.net/1721.1/105027"],"dc:language.iso":["eng"],"dc:publisher":["Massachusetts Institute of Technology"],"dc:rights":["M.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."],"dc:rights.uri":["http://dspace.mit.edu/handle/1721.1/7582"],"dc:subject":["Chemistry."],"dc:title":["Molecular mechanisms of synaptic plasticity"],"dc:type":["Thesis"]},"updated_at":"2026-07-22T22:22:20Z"}