Estrogens Rapidly Enhance Neural Plasticity and Learning

dc.contributor.advisorCholeris, Elena
dc.contributor.advisorMacLusky, Neil
dc.contributor.authorPhan, Anna
dc.date.accessioned2013-07-24T14:42:06Z
dc.date.available2013-07-24T14:42:06Z
dc.date.copyright2013-07
dc.date.created2013-06-21
dc.date.issued2013-07-24
dc.degree.departmentDepartment of Psychologyen_US
dc.degree.grantorUniversity of Guelphen_US
dc.degree.nameDoctor of Philosophyen_US
dc.degree.programmeNeuroscienceen_US
dc.description.abstractThis thesis examines the rapid, non-genomic effects of estrogens on neural plasticity and learning. Estrogens are classically known to affect gene transcription events, however they have more recently been found to also rapidly activate second messenger systems within 1hr of administration. Therefore, we first examined the rapid effects of 17β-estradiol, and an estrogen receptor (ER) α and ERβ agonist on three different learning paradigms: object placement, object recognition, and social recognition. We found that both systemic injections and intrahippocampal delivery of 17β-estradiol and the ERα agonist improved performance on all 3 learning paradigms within 40min of hormone administration. However, the ERβ agonist administered systemically or intrahippocampally, improved performance only on the object placement learning paradigm, while having no effect on object recognition, and impairing social recognition at high doses. To elucidate how estrogens might rapidly affect learning, we examined how estrogens rapidly affect the neural plasticity of CA1 hippocampal neurons. We found that 17β-estradiol and the ERα agonist increased dendritic spine density in CA1 hippocampal neurons within 40min of administration, suggesting that estrogens rapidly increase the density of synapses within this brain region. Conversely, the ERβ agonist did not affect spine density, or decreased spine density. In addition, by using whole-cell patch clamp recordings of CA1 pyramidal neurons, we were able to determine that 17β-estradiol and the ERα agonist rapidly reduced AMPA receptor (but not NMDA receptor) mediated membrane depolarizations after 15min of hormone application. Similar to above, the ERβ agonist had no effect on AMPA or NMDA receptor mediated membrane depolarizations. These data suggest that estrogens rapidly promote the development of immature synapses (which contain low levels of synaptic AMPA receptors) within the CA1 hippocampus. Immature spines provide synaptic sites at which new memories can be stored and are thought of as “learning spines” (Kasai et al, 2003). Therefore, estrogens (through ERα) may rapidly induce the formation of hippocampal immature spines to promote learning.en_US
dc.description.sponsorshipNatural Sciences and Engineering Research Council of Canada
dc.identifier.urihttp://hdl.handle.net/10214/7288
dc.language.isoenen_US
dc.publisherUniversity of Guelphen_US
dc.rights.licenseAll items in the Atrium are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectEstrogenen_US
dc.subjectEstradiolen_US
dc.subjectLearningen_US
dc.subjectMemoryen_US
dc.subjectObject Placementen_US
dc.subjectObject Recognitionen_US
dc.subjectSocial Recognitionen_US
dc.subjectNon-genomicen_US
dc.subjectAMPAen_US
dc.subjectNMDAen_US
dc.subjectDendritic Spinesen_US
dc.subjectElectrophysiologyen_US
dc.subjectLTPen_US
dc.subjectLTDen_US
dc.subjectHippocampusen_US
dc.subjectCA1en_US
dc.subjectGPERen_US
dc.subjectERαen_US
dc.subjectERβen_US
dc.subjectMiceen_US
dc.subjectImmature synapseen_US
dc.subjectSynaptic plasticityen_US
dc.subjectStructural plasticityen_US
dc.subjectGlutamateen_US
dc.subjectLearning spineen_US
dc.subjectMemory spineen_US
dc.titleEstrogens Rapidly Enhance Neural Plasticity and Learningen_US
dc.typeThesisen_US

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