Show simple item record

dc.contributor.authorPodor, Borbala
dc.date.accessioned2017-08-03T14:03:29Z
dc.date.available2017-08-03T14:03:29Z
dc.identifier.urihttp://hdl.handle.net/10222/73089
dc.description.abstractSynaptic plasticity refers to changes in the strength of connections between neurons in response to previous activity. Its experimental correlates, i.e., long-term-potentiation (LTP), a persistent increase in synaptic efficacy, and long-term-depression (LTD), a persistent decrease in synaptic efficacy, are the leading cellular models of learning and memory. The observed changes in LTP and LTD are detected by electrophysiological methods as lasting modifications of synaptic transmission, but they may be accompanied by morphological changes in the synapses undergoing plasticity. However, published accounts of the relationship between functional and structural changes are incomplete and often inconsistent. This is partially due to the lack of available tools and technologies allowing direct observations and interpretations of obtained results. In this thesis I explore potential technological advances for investigating neuronal activity, and examine the relationship of functional and structural changes at synapses undergoing plasticity. First, I evaluate a number of novel genetically-encoded calcium indicators (GECIs) for optical monitoring of neuronal activity in rat hippocampal slices. The results indicate that most GECIs are too slow and/or insensitive to follow individual action potentials at high frequencies necessary for some intended uses. Next, I demonstrate that recently-developed ultrafast GECIs provide vastly improved kinetics, but at the expense of weaker fluorescent signals. Further improvements in these indicators may be highly valuable for future applications. Finally, I present a multifaceted approach combining double intracellular electrophysiological recordings from pairs of synaptically connected hippocampal neurons with two-photon-excitation fluorescence microscopy and calcium imaging to study structural plasticity of individually identified synapses undergoing plasticity. My results suggest that physiological stimulation and plasticity induction do not cause significant persistent changes in size of either pre- or postsynaptic elements. In this context, I also describe how optimizing a variety of recording variables (e.g., days in vitro, sub-regional localization, distance between cell pairs) contribute to the success of paired recordings in rat organotypic hippocampal slices, and how it can aid our studies on structural and functional plasticity.en_US
dc.language.isoenen_US
dc.subjectsynaptic plasticityen_US
dc.subjectgenetically encoded calcium indicatorsen_US
dc.subjectorganotypic hippocampal sliceen_US
dc.subjecttwo-photon microscopyen_US
dc.subjectcalcium imagingen_US
dc.subjectstructural plasticityen_US
dc.subjectpaired recordingsen_US
dc.titleNOVEL APPROACHES TO THE STUDY OF SYNAPTIC PLASTICITY IN THE RAT HIPPOCAMPUSen_US
dc.date.defence2017-06-23
dc.contributor.departmentDepartment of Physiology & Biophysicsen_US
dc.contributor.degreeDoctor of Philosophyen_US
dc.contributor.external-examinerDr. Katalin Tothen_US
dc.contributor.graduate-coordinatorDr. Valerie Chappeen_US
dc.contributor.thesis-readerDr. Stefan Kruegeren_US
dc.contributor.thesis-readerDr. William Baldridgeen_US
dc.contributor.thesis-supervisorDr. Alan Fineen_US
dc.contributor.ethics-approvalReceiveden_US
dc.contributor.manuscriptsYesen_US
dc.contributor.copyright-releaseYesen_US
 Find Full text

Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record