The brain is constantly engaged in processing, maintaining, and recalling information. The ability to maintain information for a short period of time is known as working memory, and behavioral experiments in vivo have highlighted the role of persistent neural activity in several brain regions, including the hippocampus, in encoding information during working memory tasks. However, how that persistent activity arises in vivo is currently unknown. Recently, it was shown in hippocampal brain slices that persistent activity can be evoked in the dentate gyrus. In response to brief stimulation of the perforant path, semilunar granule cells exhibit intrinsic plateau depolarizations driven by NMDAR and L- and T-type voltage-dependent calcium channel conductances, driving persistent synaptic barrages onto hilar cells. These barrages last for 10s of seconds, resembling the persistent activity observed in vivo during working memory tasks. In this dissertation, I test the hypothesis that this in vitro preparation can maintain information for multiple stimulus locations over 10 seconds, as required by neural circuits engaged in vivo during working memory tasks. As the hippocampal formation is known to maintain the identity of information context as well as content, I also test the hypothesis that this preparation is able to maintain representation of stimuli presented in sequences separated by short intervals. Finally, I examine the robustness of this in vitro preparation to small perturbations in sequence interval and test the hypothesis that both stimulus and sequence representations are maintained by a population code.
In the first chapter of this dissertation I discuss classic studies on the neurobiology of memory and the anatomical organization of brain regions, especially the hippocampal formation, involved in mnemonic representations of experience. I then discuss how persistent activity has emerged as the neural correlate of working memory, and how experimental and computational studies of persistent activity have sought to uncover its origins in several cellular and network mechanisms. In the last part of the chapter I discuss experimental studies of maintaining the context of sequential information.
In the second chapter, I discuss the results of investigating my hypothesis that small cell assemblies of the dentate hilus can maintain the identity of a stimulus. I demonstrate that stimulus representations decay over time, and I show that the network can respond to individual stimuli as well as sequences of stimuli. I discuss results suggesting that persistent activity in the dentate gyrus enables hilar cells to maintain noncommutative representations of sequential stimuli. These results implicate the dentate gyrus as a short-term processor of both individual stimuli as well as stimuli occurring in specific contexts.
In the final chapter, I discuss what previous computational and experimental studies have indicated might be required of the properties of individual cells and their organization into networks to allow the maintenance of these various forms of information. Finally, in the last section of that chapter I will suggest a hypothetical mechanism whereby the dentate hilus can encode the spatio-temporal patterns of stimuli reported in this dissertation.
","abstract_html":"<p>The brain is constantly engaged in processing, maintaining, and recalling information. The ability to maintain information for a short period of time is known as working memory, and behavioral experiments in vivo have highlighted the role of persistent neural activity in several brain regions, including the hippocampus, in encoding information during working memory tasks. However, how that persistent activity arises in vivo is currently unknown. Recently, it was shown in hippocampal brain slices that persistent activity can be evoked in the dentate gyrus. In response to brief stimulation of the perforant path, semilunar granule cells exhibit intrinsic plateau depolarizations driven by NMDAR and L- and T-type voltage-dependent calcium channel conductances, driving persistent synaptic barrages onto hilar cells. These barrages last for 10s of seconds, resembling the persistent activity observed in vivo during working memory tasks. In this dissertation, I test the hypothesis that this in vitro preparation can maintain information for multiple stimulus locations over 10 seconds, as required by neural circuits engaged in vivo during working memory tasks. As the hippocampal formation is known to maintain the identity of information context as well as content, I also test the hypothesis that this preparation is able to maintain representation of stimuli presented in sequences separated by short intervals. Finally, I examine the robustness of this in vitro preparation to small perturbations in sequence interval and test the hypothesis that both stimulus and sequence representations are maintained by a population code.</p><p>In the first chapter of this dissertation I discuss classic studies on the neurobiology of memory and the anatomical organization of brain regions, especially the hippocampal formation, involved in mnemonic representations of experience. I then discuss how persistent activity has emerged as the neural correlate of working memory, and how experimental and computational studies of persistent activity have sought to uncover its origins in several cellular and network mechanisms. In the last part of the chapter I discuss experimental studies of maintaining the context of sequential information. </p><p>In the second chapter, I discuss the results of investigating my hypothesis that small cell assemblies of the dentate hilus can maintain the identity of a stimulus. I demonstrate that stimulus representations decay over time, and I show that the network can respond to individual stimuli as well as sequences of stimuli. I discuss results suggesting that persistent activity in the dentate gyrus enables hilar cells to maintain noncommutative representations of sequential stimuli. These results implicate the dentate gyrus as a short-term processor of both individual stimuli as well as stimuli occurring in specific contexts. </p><p>In the final chapter, I discuss what previous computational and experimental studies have indicated might be required of the properties of individual cells and their organization into networks to allow the maintenance of these various forms of information. Finally, in the last section of that chapter I will suggest a hypothetical mechanism whereby the dentate hilus can encode the spatio-temporal patterns of stimuli reported in this dissertation.</p>","abstract_has_math":false,"creators":["Hyde, Robert A."],"institution":"Case Western Reserve University School of Graduate Studies","degree_name":"Doctor of Philosophy","degree_level":"doctoral","degree_discipline":"Neurosciences","degree_department":null,"school":null,"contributors":["Strowbridge, Ben","Kunze, Diana"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-03-08","date_published":"2013-03-08","updated_at":"2026-07-24T03:35:52Z","subjects":["Neurosciences","working memory","temporal sequences","patch clamp","persistent activity","semilunar granule cells","dentate gyrus","local circuits"],"languages":["English"],"rights":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://rave.ohiolink.edu/etdc/view?acc_num=case1352773632","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Strowbridge, Ben","Kunze, Diana"]},{"key":"dc:creator","label":"Author","values":["Hyde, Robert A."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013-03-08"]},{"key":"dc:publisher","label":"Institution","values":["Case Western Reserve University School of Graduate Studies / OhioLINK"]},{"key":"dc:type","label":"Dc Type","values":["Electronic Thesis or Dissertation"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Neurosciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Case Western Reserve University School of Graduate Studies"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Neurosciences","working memory","temporal sequences","patch clamp","persistent activity","semilunar granule cells","dentate gyrus","local circuits"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:rights","label":"Dc Rights","values":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://rave.ohiolink.edu/etdc/view?acc_num=case1352773632"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The brain is constantly engaged in processing, maintaining, and recalling information. The ability to maintain information for a short period of time is known as working memory, and behavioral experiments in vivo have highlighted the role of persistent neural activity in several brain regions, including the hippocampus, in encoding information during working memory tasks. However, how that persistent activity arises in vivo is currently unknown. Recently, it was shown in hippocampal brain slices that persistent activity can be evoked in the dentate gyrus. In response to brief stimulation of the perforant path, semilunar granule cells exhibit intrinsic plateau depolarizations driven by NMDAR and L- and T-type voltage-dependent calcium channel conductances, driving persistent synaptic barrages onto hilar cells. These barrages last for 10s of seconds, resembling the persistent activity observed in vivo during working memory tasks. In this dissertation, I test the hypothesis that this in vitro preparation can maintain information for multiple stimulus locations over 10 seconds, as required by neural circuits engaged in vivo during working memory tasks. As the hippocampal formation is known to maintain the identity of information context as well as content, I also test the hypothesis that this preparation is able to maintain representation of stimuli presented in sequences separated by short intervals. Finally, I examine the robustness of this in vitro preparation to small perturbations in sequence interval and test the hypothesis that both stimulus and sequence representations are maintained by a population code.
In the first chapter of this dissertation I discuss classic studies on the neurobiology of memory and the anatomical organization of brain regions, especially the hippocampal formation, involved in mnemonic representations of experience. I then discuss how persistent activity has emerged as the neural correlate of working memory, and how experimental and computational studies of persistent activity have sought to uncover its origins in several cellular and network mechanisms. In the last part of the chapter I discuss experimental studies of maintaining the context of sequential information.
In the second chapter, I discuss the results of investigating my hypothesis that small cell assemblies of the dentate hilus can maintain the identity of a stimulus. I demonstrate that stimulus representations decay over time, and I show that the network can respond to individual stimuli as well as sequences of stimuli. I discuss results suggesting that persistent activity in the dentate gyrus enables hilar cells to maintain noncommutative representations of sequential stimuli. These results implicate the dentate gyrus as a short-term processor of both individual stimuli as well as stimuli occurring in specific contexts.
In the final chapter, I discuss what previous computational and experimental studies have indicated might be required of the properties of individual cells and their organization into networks to allow the maintenance of these various forms of information. Finally, in the last section of that chapter I will suggest a hypothetical mechanism whereby the dentate hilus can encode the spatio-temporal patterns of stimuli reported in this dissertation.
"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf","p.161","4.73 MB"]},{"key":"dc:title","label":"Title","values":["Mnemonic Representations of Transient Stimuli and Temporal Sequences in the Rodent Dentate Gyrus In Vitro"]}]}],"canonical_facts":{"dc:contributor":["Strowbridge, Ben","Kunze, Diana"],"dc:creator":["Hyde, Robert A."],"dc:date":["2013-03-08"],"dc:description":["The brain is constantly engaged in processing, maintaining, and recalling information. The ability to maintain information for a short period of time is known as working memory, and behavioral experiments in vivo have highlighted the role of persistent neural activity in several brain regions, including the hippocampus, in encoding information during working memory tasks. However, how that persistent activity arises in vivo is currently unknown. Recently, it was shown in hippocampal brain slices that persistent activity can be evoked in the dentate gyrus. In response to brief stimulation of the perforant path, semilunar granule cells exhibit intrinsic plateau depolarizations driven by NMDAR and L- and T-type voltage-dependent calcium channel conductances, driving persistent synaptic barrages onto hilar cells. These barrages last for 10s of seconds, resembling the persistent activity observed in vivo during working memory tasks. In this dissertation, I test the hypothesis that this in vitro preparation can maintain information for multiple stimulus locations over 10 seconds, as required by neural circuits engaged in vivo during working memory tasks. As the hippocampal formation is known to maintain the identity of information context as well as content, I also test the hypothesis that this preparation is able to maintain representation of stimuli presented in sequences separated by short intervals. Finally, I examine the robustness of this in vitro preparation to small perturbations in sequence interval and test the hypothesis that both stimulus and sequence representations are maintained by a population code.
In the first chapter of this dissertation I discuss classic studies on the neurobiology of memory and the anatomical organization of brain regions, especially the hippocampal formation, involved in mnemonic representations of experience. I then discuss how persistent activity has emerged as the neural correlate of working memory, and how experimental and computational studies of persistent activity have sought to uncover its origins in several cellular and network mechanisms. In the last part of the chapter I discuss experimental studies of maintaining the context of sequential information.
In the second chapter, I discuss the results of investigating my hypothesis that small cell assemblies of the dentate hilus can maintain the identity of a stimulus. I demonstrate that stimulus representations decay over time, and I show that the network can respond to individual stimuli as well as sequences of stimuli. I discuss results suggesting that persistent activity in the dentate gyrus enables hilar cells to maintain noncommutative representations of sequential stimuli. These results implicate the dentate gyrus as a short-term processor of both individual stimuli as well as stimuli occurring in specific contexts.
In the final chapter, I discuss what previous computational and experimental studies have indicated might be required of the properties of individual cells and their organization into networks to allow the maintenance of these various forms of information. Finally, in the last section of that chapter I will suggest a hypothetical mechanism whereby the dentate hilus can encode the spatio-temporal patterns of stimuli reported in this dissertation.
"],"dc:format":["application/pdf","p.161","4.73 MB"],"dc:identifier":["http://rave.ohiolink.edu/etdc/view?acc_num=case1352773632"],"dc:language":["English"],"dc:publisher":["Case Western Reserve University School of Graduate Studies / OhioLINK"],"dc:rights":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."],"dc:subject":["Neurosciences","working memory","temporal sequences","patch clamp","persistent activity","semilunar granule cells","dentate gyrus","local circuits"],"dc:title":["Mnemonic Representations of Transient Stimuli and Temporal Sequences in the Rodent Dentate Gyrus In Vitro"],"dc:type":["Electronic Thesis or Dissertation"],"thesis:degree_discipline":["Neurosciences"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["Case Western Reserve University School of Graduate Studies"]},"updated_at":"2026-07-24T03:35:52Z"}