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논문 기본 정보

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학위논문
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신효근 (과학기술연합대학원대학교, 과학기술연합대학원)

지도교수
조일주
발행연도
2021
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과학기술연합대학원대학교 논문은 저작권에 의해 보호받습니다.

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이 논문의 연구 히스토리 (2)

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뇌 기능을 이해하고, 뇌질환의 원인을 규명하기 위해서는 기능적으로 연결된 뇌회로에 정밀하게 접속하여 세포 수준에서 신경 회로를 탐색하고 제어하는 것이 필수적이다. 이를 위해, 최근에는 신경신호의 기록과 함께 광학 자극 및 약물 전달 기능을 갖춘 다기능 신경 프로브들이 개발되었다. 이러한 프로브는 뇌 안의 신경 세포를 정밀하게 자극하고, 이에 따른 활성화된 신경 활동을 기록하여 특정 뇌 영역의 정밀한 분석을 가능하게 하였다. 그러나 기존의 다기능 신경 프로브들은 구조적인 한계로 인해 국소부위의 뇌영역에만 접속할 수 있어, 여러 뇌 영역 간의 기능적 연결성을 분석하는 데에 한계가 있었다. 이러한 기존 소자들의 문제를 해결하기 위해, 본 연구에서는 뇌회로의 여러 영역에 동시 접속하여 신경신호를 기록하고, 정밀하게 자극할 수 있는 다기능 신경 프로브 어레이를 제안한다. MEMS 공정을 이용하여, 제작된 다기능 프로브는 생쥐의 뇌 또는 3차원 체외 신경망 모델내 여러 뇌신경 영역에 정밀하게 접속하여 영역간 기능적 연결에 대한 정확한 분석을 가능하게 하였다. 또한, 미세 유체 채널 및 광 도파로가 모놀리식한 구조로 통합된 프로브는 40 μm의 얇은 두께로 제작되어, 기존 다기능 프로브들에 비해 삽입시 뇌 손상을 최소화하였다. 추가적으로, 본 연구에서는 고차원적 뇌회로 연구에 필수적인 자유롭게 행동하는 동물에서 신경 회로 분석을 위한 초소형 무선 뉴럴 프로브 시스템을 제시한다. 이 시스템은 초경량으로 설계 및 제작되어 생쥐의 행동에 미치는 영향을 최소화하였다. 또한, 시스템 내 블루투스 무선통신 프로토콜을 적용하여 여러 마리의 생쥐에서 동시에 신경 신호를 성공적으로 측정하였고, 그 결과 사회성 행동과 관련된 뇌회로 연구에 활용 가능성을 입증하였다. 결론적으로, 본 학위 논문에서 제안한 다기능 뉴럴 프로브 시스템은 다양한 신경 회로 연구에 광범위하게 활용될 것으로 기대한다.

목차

Contents
1. Introduction ····························································· 1
1.1 Neural circuit: in vivo and in vitro ······························· 1
1.2 MEMS neural probe for investigating neural circuits ········· 2
1.3 Method for modulating neural circuits ·························· 4
1.4 Multifunctional neural probe ····································· 5
1.5 Approach for investigating and modulating neural circuits ·· 7
2. Multifunctional multi shank neural probe for investigating and modulating long-range neural circuit in vivo··············· 9
2.1 Summary ···························································· 9
2.2 Fabrication and characterizations of multifunctional multi-shank neural probe ················································· 10
2.2.1 Design of multifunctional multi-shank neural probe ··· 10
2.2.2 Fabrication and packaging of multifunctional multi-shank neural probe ················································· 11
2.2.3 Characterizations of multifunctional multi-shank neural probe ························································· 16
2.3 In vivo demonstration of multifunctional neural probe ······· 20
2.3.1 Immune responses by the multifunctional probe in the brain ································································· 20
2.3.2 Localized optical stimulation with multifunctional probe array ·························································· 25
2.4 Investigation and modulation of hippocampal CA3 and CA1 circuit ································································ 28
2.4.1 Investigation of hippocampal CA3 and CA1 connectivity ························································· 28
2.4.2 Modulation of hippocampal CA3 and CA1 connectivity ························································· 32
2.5 Discussion and conclusion ········································ 36
3. 3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics in vitro······················································· 38
3.1 Summary ···························································· 38
3.2 Fabrication and characterizations of the 3D multifunctional MEA ································································· 39
3.2.1 Fabrication of the 3D multifunctional MEA ············ 39
3.2.2 Packaging of the 3D multifunctional MEA ·············· 42
3.2.3 Characterizations of the 3D multifunctional MEA ····· 44
3.2.4 The system assembly ······································· 47
3.3 3D neural culture on the 3D multifunctional MEA system ·· 48
3.3.1 Culture method of the single-group and two-group 3D neural network models ············································ 48
3.3.2 The single-group and two-group 3D neural network models ······························································· 51
3.4 Investigation of neural circuit dynamics in the single-group and two-group 3D neural network models ····················· 53
3.4.1 Neural network changes in the single-group 3D neural network model ······················································ 53
3.4.2 Analysis of neural circuit dynamics by local stimulation in the single-group 3D neural network model ··· 59
3.4.3 Functional connectivity between somatic regions in the two-group 3D neural network model ······················· 65
3.5 Discussion and conclusion ········································ 72
4. Wireless neural probe system for investigating neural circuits in freely behaving mice······································ 74
4.1 Summary ···························································· 74
4.2 Design and fabrication of wireless neural probe system ······ 75
4.2.1 Design of wireless neural recording system ············· 75
4.2.2 Packaging of wireless neural probe system ·············· 78
4.3 In vivo demonstration of wireless neural probe system ······ 78
4.3.1 Recording performance of wireless neural probe system ······························································· 78
4.3.2 Recording distance and long-term recording of wireless neural probe system ····································· 81
4.3.3 Open-field test ··············································· 82
4.3.4 Simultaneous recording from the multiple mice ········ 84
4.4 Discussion and conclusion ········································ 86
5. Conclusion ······························································· 88
5.1 Summary ···························································· 88
5.2 Outlook ······························································ 90
Reference ································································· 92

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