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Studies on cognitive behavior in normal and disease model mice using touch screen-based operant conditioning

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dc.contributor.advisor강봉균-
dc.contributor.author곽철정-
dc.date.accessioned2017-07-14T00:51:57Z-
dc.date.available2017-07-14T00:51:57Z-
dc.date.issued2016-02-
dc.identifier.other000000132681-
dc.identifier.urihttps://hdl.handle.net/10371/121442-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 생명과학부, 2016. 2. 강봉균.-
dc.description.abstractTouch screen test is a recently developed cognition testing tool. Based on operant conditioning, touch screen test enables to test cognition of animals by scoring their cognitive response to visual stimulus presented on LCD monitor. Compared to traditional cognition testing tools, touch screen test has its own advantage in testing cognitions of animals, such as automaticity, the variety of testing cognition types, and translation to human cognition.
In spite of these advantages, the real value of touch screen as a cognition testing tool is not fully proven yet. Until a recent date, touch screen has been mostly used to examine the functional roles of a brain region in the specific cognition or to reveal cognitive impairment in transgenic animals, all of which are also possible to investigate by traditional cognition testing tools.
In this study, I evaluated the use of touch screen as a tool of testing mices cognition with more detail and multiple purposes. To do this, I first showed that mice can perform delayed match to location based working memory task in touch screen. I also showed that touch screen can not only assess working memory itself, but also measure the reaction time of animals during cognitive decision with high accuracy. I found that slight but very significant different reaction time between when mice made correct and incorrect choice, which may have important implication.
I also combined touch screen with optogenetics tool to trigger laser output in automatic and programmed manner. With this automatic optogenetic tool, I tested whether optogenetic activation of dopaminergic neurons can reinforce touching behavior without any natural reward. I first injected adeno-associated virus (AAV) encoding channelrhodopsin 2 (ChR2) into ventral tegmental area (VTA) of tyrosine hydroxylase-cre (TH-cre) mice, to express ChR2 specifically in dopaminergic neurons in VTA. I also designed to trigger optogenetic laser output in contingent with touching visual stimulus. I found that automatic and touch screen mediated optogenetic activation can reinforce touching behavior without any natural reward.
Finally, I investigated cognition disability of Parkinson disease (PD) model animal. Conventional cognition testing tools have limitations in testing cognitions of animal models which have motor impairments. By virtue of low motor demand of touch screen test, I could assess cognitive disability of PD model animals in spite of their motor output deficits.
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dc.description.tableofcontentsIntroduction 8
Assessment of Cognition by Touch screen test 8
Advantages of touch screen test 8
Optogenetics 10
Purpose 15

Chapter 1 Development of a touch-screen-based paradigm for assessing working memory in the mouse 16
Abstract 17
Introduction 18
Materials and Methods 20
Results 23
Discussion 33

Chapter 2 Reinforcement of touching behavior by touch screen based automatic optogenetics tool 35
Abstract 36
Introduction 37
Materials and Methods 39
Results 42
Discussion 50

Chapter 3 Assessments of cognitive abilities in a mouse model of Parkinsons disease with touch screen test 53
Abstract 54
Introduction 55
Materials and Methods 58
Results 65
Discussion 89

References 94

국문 초록 98
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dc.formatapplication/pdf-
dc.format.extent1519790 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectTouch screen-
dc.subjectWorking memory-
dc.subjectDelayed match to location-
dc.subjectOptogenetics-
dc.subjectReinforcement-
dc.subjectVentral tegmental area-
dc.subjectChannelrhodopsin-
dc.subjectReversal learning-
dc.subjectattention-
dc.subject5 choice serial reaction time (5-CSRT)-
dc.subjectlocation discrimination-
dc.subjectParkinson-
dc.subject.ddc570-
dc.titleStudies on cognitive behavior in normal and disease model mice using touch screen-based operant conditioning-
dc.typeThesis-
dc.description.degreeDoctor-
dc.citation.pages99-
dc.contributor.affiliation자연과학대학 생명과학부-
dc.date.awarded2016-02-
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