{"id":{"repo_id":"montana-tech","oai_identifier":"oai:scholarworks.umt.edu:etd-2013"},"canonical_url":"https://search.dev.ndltd.org/etd/montana-tech/oai:scholarworks.umt.edu:etd-2013","repository":{"repo_id":"montana-tech","name":"Montana Technology","base_url":"https://scholarworks.umt.edu/do/oai/"},"display":{"title":"THE EFFECT OF SPILLOVER ONTO IONOTROPIC GLUTAMATE RECEPTORS AT THE SCHAFFER-CA1 SYNAPSE IN HIPPOCAMPAL SLICE","abstract":"Glutamate is the major excitatory neurotransmitter in the brain and is crucial for processes such as learning and memory. Due its importance as a signaling molecule, the extracellular glutamate concentration is tightly regulated, largely by the excitatory amino-acid transporters (EAATs). In these studies, we investigated the role of EAAT1-3 in synaptic transmission at the Schaffer-CA1 synapse in acute hippocampal brain slices. My results demonstrated that transport block by L-TBA resulted in glutamate spillover and activation of NMDARs. Further investigation showed that L-TBA-mediated activation of NMDARs was facilitated by the Mg2+ unblock of the receptor. Furthermore our data indicate that NMDAR signaling was controlled by the interplay between several factors, including synaptic frequency, glutamate transport, Mg2+ block, and NMDAR channel kinetics. We propose that the observed theta frequency threshold for enhanced NMDAR signaling observed in physiological conditions is a consequence of a phase shifted signal at rhythms limited by NMDAR channel kinetics. We also found that dense fiber recruitment created conditions of spillover and glutamate pooling and therefore resulted in an increase in AMPAR desensitization at the hippocampal Schaffer-CA1 synapse. Overall my studies focused on the effects of glutamate spillover onto both NMDA and AMPA receptors at the Schaffer-CA1 synapse in hippocampal slice.","abstract_html":"Glutamate is the major excitatory neurotransmitter in the brain and is crucial for processes such as learning and memory. Due its importance as a signaling molecule, the extracellular glutamate concentration is tightly regulated, largely by the excitatory amino-acid transporters (EAATs). In these studies, we investigated the role of EAAT1-3 in synaptic transmission at the Schaffer-CA1 synapse in acute hippocampal brain slices. My results demonstrated that transport block by L-TBA resulted in glutamate spillover and activation of NMDARs. Further investigation showed that L-TBA-mediated activation of NMDARs was facilitated by the Mg2+ unblock of the receptor. Furthermore our data indicate that NMDAR signaling was controlled by the interplay between several factors, including synaptic frequency, glutamate transport, Mg2+ block, and NMDAR channel kinetics. We propose that the observed theta frequency threshold for enhanced NMDAR signaling observed in physiological conditions is a consequence of a phase shifted signal at rhythms limited by NMDAR channel kinetics. We also found that dense fiber recruitment created conditions of spillover and glutamate pooling and therefore resulted in an increase in AMPAR desensitization at the hippocampal Schaffer-CA1 synapse. Overall my studies focused on the effects of glutamate spillover onto both NMDA and AMPA receptors at the Schaffer-CA1 synapse in hippocampal slice.","abstract_has_math":false,"creators":["Hoffman, Katie Marie"],"institution":"University of Montana","degree_name":"Doctor of Philosophy (PhD)","degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-01-01T08:00:00Z","date_published":"2012-01-01T08:00:00Z","updated_at":"2026-07-24T03:14:06Z","subjects":["EAATs","glutamate","NMDARs"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholarworks.umt.edu/etd/994","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Hoffman, Katie Marie"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:publisher","label":"Institution","values":["University of Montana"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["EAATs","glutamate","NMDARs"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarworks.umt.edu/etd/994"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Glutamate is the major excitatory neurotransmitter in the brain and is crucial for processes such as learning and memory. Due its importance as a signaling molecule, the extracellular glutamate concentration is tightly regulated, largely by the excitatory amino-acid transporters (EAATs). In these studies, we investigated the role of EAAT1-3 in synaptic transmission at the Schaffer-CA1 synapse in acute hippocampal brain slices. My results demonstrated that transport block by L-TBA resulted in glutamate spillover and activation of NMDARs. Further investigation showed that L-TBA-mediated activation of NMDARs was facilitated by the Mg2+ unblock of the receptor. Furthermore our data indicate that NMDAR signaling was controlled by the interplay between several factors, including synaptic frequency, glutamate transport, Mg2+ block, and NMDAR channel kinetics. We propose that the observed theta frequency threshold for enhanced NMDAR signaling observed in physiological conditions is a consequence of a phase shifted signal at rhythms limited by NMDAR channel kinetics. We also found that dense fiber recruitment created conditions of spillover and glutamate pooling and therefore resulted in an increase in AMPAR desensitization at the hippocampal Schaffer-CA1 synapse. Overall my studies focused on the effects of glutamate spillover onto both NMDA and AMPA receptors at the Schaffer-CA1 synapse in hippocampal slice."]},{"key":"dc:title","label":"Title","values":["THE EFFECT OF SPILLOVER ONTO IONOTROPIC GLUTAMATE RECEPTORS AT THE SCHAFFER-CA1 SYNAPSE IN HIPPOCAMPAL SLICE"]}]}],"canonical_facts":{"dc:creator":["Hoffman, Katie Marie"],"dc:description.abstract":["Glutamate is the major excitatory neurotransmitter in the brain and is crucial for processes such as learning and memory. Due its importance as a signaling molecule, the extracellular glutamate concentration is tightly regulated, largely by the excitatory amino-acid transporters (EAATs). In these studies, we investigated the role of EAAT1-3 in synaptic transmission at the Schaffer-CA1 synapse in acute hippocampal brain slices. My results demonstrated that transport block by L-TBA resulted in glutamate spillover and activation of NMDARs. Further investigation showed that L-TBA-mediated activation of NMDARs was facilitated by the Mg2+ unblock of the receptor. Furthermore our data indicate that NMDAR signaling was controlled by the interplay between several factors, including synaptic frequency, glutamate transport, Mg2+ block, and NMDAR channel kinetics. We propose that the observed theta frequency threshold for enhanced NMDAR signaling observed in physiological conditions is a consequence of a phase shifted signal at rhythms limited by NMDAR channel kinetics. We also found that dense fiber recruitment created conditions of spillover and glutamate pooling and therefore resulted in an increase in AMPAR desensitization at the hippocampal Schaffer-CA1 synapse. Overall my studies focused on the effects of glutamate spillover onto both NMDA and AMPA receptors at the Schaffer-CA1 synapse in hippocampal slice."],"dc:identifier":["https://scholarworks.umt.edu/etd/994"],"dc:publisher":["University of Montana"],"dc:subject":["EAATs","glutamate","NMDARs"],"dc:title":["THE EFFECT OF SPILLOVER ONTO IONOTROPIC GLUTAMATE RECEPTORS AT THE SCHAFFER-CA1 SYNAPSE IN HIPPOCAMPAL SLICE"],"dc:type":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T03:14:06Z"}