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Tissue Engineered Multi-Aggregate Cortical-Hippocampal Neural Networks for Pharmacological Investigations
Tissue Engineered Multi-Aggregate Cortical-Hippocampal Neural Networks for Pharmacological Investigations
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151024
- ISBN
- 9798382829944
- DDC
- 616
- 서명/저자
- Tissue Engineered Multi-Aggregate Cortical-Hippocampal Neural Networks for Pharmacological Investigations
- 발행사항
- [Sl] : University of Pennsylvania, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 404 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Advisor: Cullen, Kacy;Kording, Konrad.
- 학위논문주기
- Thesis (Ph.D.)--University of Pennsylvania, 2024.
- 초록/해제
- 요약Cortical-hippocampal networks are crucial for integrating multisensory experiences into distinct, enduring memories and facilitating memory retrieval. Despite advances in understanding hippocampal function through various experimental techniques and animal models, the complexity of these in vivo networks remains a challenge, and their low-throughput limits utility in pharmacological research. In vitro models, particularly 2D cultures, offer simplified systems for studying hippocampal networks and are low-cost, high-throughput testbeds. However, they fall short in recapitulating key aspects of the native microenvironment, thus their network properties are too dissimilar and their translational value is limited. In this dissertation, we applied tissue engineering techniques to develop biofidelic multi-cellular cortical-hippocampal neural networks as novel models and testbeds for scientific investigations. We employed a forced aggregation technique to generate high-density (100,000 cells/mm3) multi-cellular three-dimensional (3D) aggregates using rodent embryonic hippocampal tissue. We compared the structural and functional properties of aggregated (3D) and dissociated (2D) cultures over 28 days in vitro (DIV). Aggregates exhibited robust axonal fasciculation, significant neuronal polarization at earlier time points, and astrocytes forming non-overlapping quasi-domains with stellate morphologies resembling in vivo structures. Using multi-electrode arrays (MEAs), we observed that 3D networks developed highly synchronized activity with high burstiness by 28 DIV. These findings suggest that the 3D microenvironment supports emergent biofidelic properties. Building on this, we explored configurations of cortical and hippocampal aggregates to model cortical-hippocampal networks. We created three distinct four-node multi-aggregate configurations (3H1C, 2H2C, 1H3C) and characterized their morphology, structural connectivity, and electrophysiological properties. We hypothesized that distinct network configurations would produce unique emergent properties. All configurations formed robust networks with axonal tracts spanning distinct nodes and similar structural connectivity, however, astrocyte domain formation was attenuated relative to single-aggregate networks. We posit that further analysis, e.g. LME models and functional connectivity, to further characterize these systems will enhance their utility in translational research by elucidating more complex network properties at local (aggregate) and global (multi-aggregate) scales. We found configuration modulated emergent electrophysiological properties and the effects of ketamine. These findings demonstrate that neural aggregates spanned by long-projecting axonal tracts can be used as modular building blocks for complex multi-nodal network topologies.
- 일반주제명
- Neurosciences
- 일반주제명
- Biomedical engineering
- 일반주제명
- Cellular biology
- 일반주제명
- Bioengineering
- 키워드
- Neural networks
- 키워드
- Psychedelics
- 기타저자
- University of Pennsylvania Bioengineering
- 기본자료저록
- Dissertations Abstracts International. 85-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798382829944
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616
■1001 ▼aAcero, Victor Pablo.
■24510▼aTissue Engineered Multi-Aggregate Cortical-Hippocampal Neural Networks for Pharmacological Investigations
■260 ▼a[Sl]▼bUniversity of Pennsylvania▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a404 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aAdvisor: Cullen, Kacy;Kording, Konrad.
■5021 ▼aThesis (Ph.D.)--University of Pennsylvania, 2024.
■520 ▼aCortical-hippocampal networks are crucial for integrating multisensory experiences into distinct, enduring memories and facilitating memory retrieval. Despite advances in understanding hippocampal function through various experimental techniques and animal models, the complexity of these in vivo networks remains a challenge, and their low-throughput limits utility in pharmacological research. In vitro models, particularly 2D cultures, offer simplified systems for studying hippocampal networks and are low-cost, high-throughput testbeds. However, they fall short in recapitulating key aspects of the native microenvironment, thus their network properties are too dissimilar and their translational value is limited. In this dissertation, we applied tissue engineering techniques to develop biofidelic multi-cellular cortical-hippocampal neural networks as novel models and testbeds for scientific investigations. We employed a forced aggregation technique to generate high-density (100,000 cells/mm3) multi-cellular three-dimensional (3D) aggregates using rodent embryonic hippocampal tissue. We compared the structural and functional properties of aggregated (3D) and dissociated (2D) cultures over 28 days in vitro (DIV). Aggregates exhibited robust axonal fasciculation, significant neuronal polarization at earlier time points, and astrocytes forming non-overlapping quasi-domains with stellate morphologies resembling in vivo structures. Using multi-electrode arrays (MEAs), we observed that 3D networks developed highly synchronized activity with high burstiness by 28 DIV. These findings suggest that the 3D microenvironment supports emergent biofidelic properties. Building on this, we explored configurations of cortical and hippocampal aggregates to model cortical-hippocampal networks. We created three distinct four-node multi-aggregate configurations (3H1C, 2H2C, 1H3C) and characterized their morphology, structural connectivity, and electrophysiological properties. We hypothesized that distinct network configurations would produce unique emergent properties. All configurations formed robust networks with axonal tracts spanning distinct nodes and similar structural connectivity, however, astrocyte domain formation was attenuated relative to single-aggregate networks. We posit that further analysis, e.g. LME models and functional connectivity, to further characterize these systems will enhance their utility in translational research by elucidating more complex network properties at local (aggregate) and global (multi-aggregate) scales. We found configuration modulated emergent electrophysiological properties and the effects of ketamine. These findings demonstrate that neural aggregates spanned by long-projecting axonal tracts can be used as modular building blocks for complex multi-nodal network topologies.
■590 ▼aSchool code: 0175.
■650 4▼aNeurosciences
■650 4▼aBiomedical engineering
■650 4▼aCellular biology
■650 4▼aBioengineering
■653 ▼aNeural networks
■653 ▼aPsychedelics
■653 ▼aTissue engineering
■653 ▼aCortical-hippocampal networks
■690 ▼a0317
■690 ▼a0541
■690 ▼a0202
■690 ▼a0379
■71020▼aUniversity of Pennsylvania▼bBioengineering.
■7730 ▼tDissertations Abstracts International▼g85-12B.
■790 ▼a0175
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160465▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
