Brain Development and Learning: Understanding the Genesis and Elimination of Neurons and Synapses

1. 先導型通識「生活中的生命科學」 第 8 單元 大腦心智的發展學習與記憶Learning and Memory 政治大學神經科學研究所 賴桂珍老師 本著作除另有註明外，採取創用CC「姓名標示－非商業性－相同方式分享」台灣2.5版授權釋出

2. Introduction • Operation of the brain • Precise interconnections among 100 billion neurons • Brain development • Connections formed and modified • Wiring in brain • Correct pathways and targets • Fine tuning

3. The Genesis of Neurons • Development of neuronal structure • Cell proliferation; Cell migration; Cell differentiation • Cell Proliferation

4. The Genesis Of Connections • Axon Guidance • Guidance Cues; Growth cones • Chemoattractant化學吸引物; Chemorepellent化學排斥物 Wiki Ashton W. Powell, Takayuki Sassa, Yongqin Wu, Marc Tessier-Lavigne Franck Polleux

5. The Genesis Of Connections Synaptic vesicle • Synapse突觸Formation Growing axon Presynaptic active zone Postsynaptic receptro cluster Filopodium Growing axon 必恩威亞太有限公司 張景婷

6. The Elimination Of Cells And Synapses • The mechanisms of pathway formation • Large-scale reduction in neurons and synapses • Development of brain function • Balance between genesis & elimination of cells and synapses • Cell Death 政治大學蘇品諺

7. The Elimination Of Cells And Synapses • Changes in Synaptic Capacity • Synapse elimination 政治大學蘇品諺

8. Synaptic Plasticity突觸可塑性 • Long-Term Synaptic Potentiation (LTP) • Role of the NMDAR • Unique properties • Voltage-gated ion channel • Calcium-permeable glutamate NMDAR AMPAR Mg2+ Ca2+ Ca2+ Ca2+ Ca2+ WikiRuth Drdla and Jürgen Sandkühler

9. Declarativememory (Medialtemporallobe;diencephalon) Nondeclarativememory Facts Events Proceduralmemory Skillsandhabits (Striatum) Skeletalmusculature (Cerebellum) Emotionalresponse (Amygdala) Classicalconditioning 政治大學趙知章

10. Types of Memory • Long-Term, Short-Term, and Working Memory • Working memory: Temporary information storage Short-term memory Consolidation Long-term memory Sensory information Consolidation Short-term memory Time 政治大學趙知章

11. 學習（Learning） • 獲取（Acquisition） • 記憶（Memory） • 保留（Retention） • 陳述性記憶（Declarative memory） • 外顯性（explicit） • 面孔、事件 • 非陳述性記憶（Nondeclarative memory） • 內隱性（implicit） • 技能、習慣、行為

12. Types of Amnesia • Amnesia失憶症 • Memory loss related to time • Retrograde amnesia • Forget things you already knew • Anterograde amnesia • Inability to form new memories

13. The Search for the Engram • Hebb’s Cell Assembly and Memory Storage Wiki Barret Ruttan Wiki Barret Ruttan Wiki Nevit Dilmen

14. 人的大腦 感覺,味覺,閱讀 視覺 運動 智能 頂葉 額葉 枕葉 顳葉 聽覺,嗅覺

15. The Temporal Lobes and DeclarativeMemory陳述性記憶 • The Medial Temporal Lobes and Memory Processing (Cont’d) • DNMS: Delayed non-match to sample • Medial temporal structures: Important for consolidation of memory

16. The Temporal Lobes and Declarative Memory • The Diencephalon and Memory Processing • Korsakoff’s Syndrome • Symptoms: Confusion, confabulations, severe memory impairment, and apathy • Alcoholics酗酒: Develop thiamin deficiency • Leads to symptoms: Abnormal eye movements, loss of coordination, tremors • Treatment: Supplemental thiamin • Thiamin deficiency: Structural brain damage

17. The Temporal Lobes and Declarative Memory • Memory Functions of the Hippocampus海馬迴 • Role of the medial temporal lobes • Declarative memory processing or consolidation WikiMcole13

18. The Temporal Lobes and Declarative Memory • Memory Functions of the Hippocampus • Spatial Memory and Place Cells • Morris water maze水迷宮 WikiSamueljohn.de

19. The Temporal Lobes and Declarative Memory • Memory Functions of the Hippocampus • Spatial Memory and Relational Memory 政治大學蘇品諺

20. Concluding Remarks • Learning and memory • Occur throughout the brain • Memories • Duration, kind of information stored, and brain structures involved • Distinct types of memory • Different types of amnesia • Multiple brain systems for memory storage

21. Procedural Learning • Associative Learning • Classical Conditioning Beforeconditioning Afterconditioning Conditioning WikiἘπαμεινώνδας 食物 (US) => 唾液分泌 (UR) 食物 (US) + 聲音 (NS) => 唾液分泌 (UR) 聲音 (CS) => 唾液分泌 (CR)

22. Vertebrate Models of Learning • Synaptic Plasticity in the Hippocampus • LTP and LTD • Key to forming declarative memories in the brain • Anatomy of Hippocampus • Brain slice preparation: Study of LTD and LTP

23. Vertebrate Models of Learning • LTP, LTD, and Glutamate Receptor Trafficking (Cont’d) Protein Phosphatase Presynaptic Postsynaptic [Ca2+]<1 µM LFS Calcium flux Unphosphorylated synaptic protein yields LTD Phosphorylated synaptic protein yields LTP 200 msec HFS Ca2+ influx Via NMDA receptors NMDA receptor [Ca2+]> 5 µM Protein kinase 必恩威亞太有限公司 張景婷

24. The Molecular Basis of Long-Term Memory • Phosphorylation磷酸化 as a long term mechanism: Problematic (transient and turnover rates) • Persistently Active Protein Kinases • Phosphorylation maintained: Kinases stay “on” • CaMKII and LTP • Molecular switch hypothesis 政治大學蘇品諺

25. The Molecular Basis of Long-Term Memory • Protein Synthesis • Requirement of long-term memory • Synthesis of new protein • Protein Synthesis and Memory Consolidation • Protein synthesis inhibitors • Deficits in learning and memory • CREB and Memory • CREB: Cyclic AMP response element binding protein

26. The Molecular Basis of Long-Term Memory • Protein Synthesis • Structural Plasticity and Memory • Long-term memory associated with formation of new synapses • Rat in complex environment: Shows increase in number of neuron synapses by about 25%

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