1. Central Nervous System Limbic System 边缘系统

2. Introduction

3. Case A 40-year-old woman awoke from sleep and complained to her husband of an indescribable unpleasant odor, nausea, and a panicky, fearful sensation. During the following week, she had repeated stereotyped episodes of this kind followed by decreased responsiveness and slow, inappropriate speech lasting 2 to 3 minutes. A 40-year-old woman awoke from sleep and complained to her husband of an indescribable unpleasant odor, nausea, and a panicky, fearful sensation. During the following week, she had repeated stereotyped episodes of this kind followed by decreased responsiveness and slow, inappropriate speech lasting 2 to 3 minutes. As we shall see, abnormalities can cause paroxysmal disorders as seen in this patient. In this chapter we will learn about this important and diverse neural system and the consequences of limbic system damage or dysfunction. As we shall see, limbic system abnormalities can cause paroxysmal disorders as seen in this patient. In this chapter we will learn about this important and diverse neural system and the consequences of limbic system damage or dysfunction.

4. History Paul Broca (1824-1880): a French physician, surgeon,anatomist, and anthropologist. He is best known for his research on Broca's area, a region of the frontal lobe that has been named after him. The term “le grand lobe limbique” （边缘叶） was first used by Broca in 1878.

6. James Papez (1883-1958): an American neuroanatomist He is most famous for his 1937 description of the Papez circuit which is a neural pathway in the brain thought to be involved in the cortical control of emotion.

7. Papez Circuit (Emotions) Mammillary bodies Other hypothalamic nuclei Septal nuclei Substantia innominata (Basal nucleus of Meynert) Hippocampal Formation (hippocampus and dentate gyrus) Anterior Thalamic nuclear group Cortex of Cingulate GyrusParahippocampal Gyrus Neocortex Fornix Mammillothalamic tract

9. Paul D. MacLean (1913-2007) an American physician and neuroscientist who made significant contributions in the fields of physiology, psychiatry, and brain research. ‘limbic system’ The term ‘limbic system’ was first used by MacLean in 1952 to describe a set of structurally and functionally related structures of the brain bordering the midline, inner surface of each cerebral hemisphere.

10. The LIMBIC SYSTEM includes diverse cortical and subcortical structures located mainly in the medial and ventral regions of the cerebral hemispheres. These structures are unified by their evolutionarily ancient origins, and they constitute the major portion of the forebrain in many species. Only in higher mammals has the larger neocortical mantle surpassed the limbic system in size. What are the limbic system ?

11. Anatomy of limbic system

12. Core component: Hippocampus and amygdala. Core component: Hippocampus and amygdala. 海马与杏仁核 海马与杏仁核 Cortex: Cingulated ， parahipocampal gyrus and prefrontal cortex. Cortex: Cingulated ， parahipocampal gyrus and prefrontal cortex. 扣带回、海马旁回与前额叶皮质 扣带回、海马旁回与前额叶皮质 Nuclei: Hippocampus, septal nuclei 隔核, amygdala, Nuclei: Hippocampus, septal nuclei 隔核, amygdala, Anterior and dorsomedial thalamus ( 丘脑前核和背内侧核 ), Anterior and dorsomedial thalamus ( 丘脑前核和背内侧核 ), Hypothalamus- mammillary body ( 下丘脑 - 乳头体）, Hypothalamus- mammillary body ( 下丘脑 - 乳头体）, Ventromedial hypothalamus （下丘脑腹内侧部）. Ventromedial hypothalamus （下丘脑腹内侧部）. Main components of the LIMBIC SYSTEM

13. The main circuit of Limbic System

14. The functions of the limbic system are also ancient, and they play an important role for survival in the animal kingdom. Limbic functions can be divided into the following four basic categories: 1. Homeostatic functions 稳态, including autonomic and neuroendocrine control 2. Olfaction 嗅觉 3. Memory 记忆 4. Emotions and drives “HOME” What are the main functions of Limbic System?

15. The other important functions of limbic System Generates emotions (Emotional brain) Generates emotions (Emotional brain) Add feeling to sensory experience which direct to behavior. Add feeling to sensory experience which direct to behavior. Affect: interpret the sensory experience as pleasant or unpleasant. Affect: interpret the sensory experience as pleasant or unpleasant. Memory and learning which is closely linked to emotion. Memory and learning which is closely linked to emotion. Sexual behavior, emotions of rage,fear, anxiety and motivation Sexual behavior, emotions of rage,fear, anxiety and motivation

16. Part 1. Amygdaloid body

18. Amygdaloid body Amygdaloid body : Large nuclear group in temporal lobe.

19. Regions of the Amygdala Large basolateral region: 基底外侧核 Large basolateral region: 基底外侧核 Provides direct input to basal ganglia and motor system. Small corticomedial group of nuclei: 皮质内侧核 Small corticomedial group of nuclei: 皮质内侧核 Related to olfactory cortex. Central nuclei: 中央核 Central nuclei: 中央核 Connected to hypothalamus.

21. Amygdala Connections Cerebral cortex Olfactory system Thalamus Brainstem reticular formation Hypothalamus AMYGDALA Stria terminalis Ventral Amygdalofugal fibers 杏仁核腹侧通路

22. Amygdala Inputs AMYGDALA Corticomedial Nuclear Group Basolateral Nuclear Group Central Nucleus Olfactory System Temporal Lobe (associated with visual, auditory, tactile senses) Brainstem (viscerosensory relay Nuclei: solitary nucleus and parabrachial nucleus) Ventral Amygdalofugal Fibers

23. Amygdala Outputs AMYGDALA Corticomedial Nuclear Group Basolateral Nuclear Group Central Nucleus Ventral Amygdalofugal Fibers Septal Nuclei Hypothalamus Dorsal Medial Thalamic Nucleus Nucleus Accumbens Hypothalamus Nuclei of ANS Ventral Amygdalofugal Fibers Stria Terminalis

24. Functions of the Amygdala Relate environmental stimuli to coordinated behavioral autonomic and endocrine responses seen in species- preservation. Relate environmental stimuli to coordinated behavioral autonomic and endocrine responses seen in species- preservation. Responses include: Responses include: Feeding and drinking Agnostic (fighting) behavior Mating and maternal care Responses to physical or emotional stresses.

25. Part 2. Hippocampus

26. Greek: “Sea Monster”

27. Hippocampus Any sensory stimulus will go to the hippocampus, and from there to the thalamus, hypothalamus and other limbic structures through FORNIX 穹窿. Any sensory stimulus will go to the hippocampus, and from there to the thalamus, hypothalamus and other limbic structures through FORNIX 穹窿. Stimulation of hippocampus can cause pleasure, rage, sex drive, etc. Stimulation of hippocampus can cause pleasure, rage, sex drive, etc. Important feature of hippocampus is that it creates prolonged response Important feature of hippocampus is that it creates prolonged response It has only three layered cortex. It has only three layered cortex. It has role in learning and memory It has role in learning and memory

28. “ C ” shaped structure in medial temporal lobe From Digital Anatomist Gross Anatomy and location

29. Morphology Another terminology mess Another terminology mess Allocortex/ archicortex 古皮质 Allocortex/ archicortex 古皮质 Hippocampal formation 海马结构 Hippocampal formation 海马结构 Dentate gyrus 齿状回 Dentate gyrus 齿状回 Hippocampus 海马 Hippocampus 海马 “ Cornu ammonis ” 阿蒙氏角 “ Cornu ammonis ” 阿蒙氏角 Subicular complex 下托 Subicular complex 下托 Entorhinal cortex 内嗅皮质 Entorhinal cortex 内嗅皮质

30. 1- hippocampal body 2 – head and digitationes hippocampi 3 – hippocampal tail 4 – fimbria (fornix) 海马伞 5 – fornix 穹隆 6 – subiculum 下托 Hippocampus

32. Neocortex greatest developed in human

33. Hippocampus of Rat

34. Development of Hippocampus From Digital Anatomist

36. Cytoarchitecture Human Rodent Two interlocking cell fields Dentate gyrus hippocampus

37. Hilus CA1-CA3: pyramidal neurons Dentate Gyrus: granule cells so sp sl sr ml sl-m Stratum oriens 始层 Stratum pyramidale 锥体层 Stratum lucidum 透明层 Stratum radiatum 辐射层 Stratum lacunosum- moleculare 网状分子层

38. Intrinsic connections Cajal, 1901 穿通纤维 谢弗侧支通路 苔藓纤维通路

39. hippocampal Network: The hippocampus forms a principally uni-directional network, with input from the Entorhinal Cortex (EC) that forms connections with the Dentate Gyrus (DG) and CA3 pyramidal neurons via the Perforant Path (PP). CA3 neurons also receive input from the DG via the Mossy Fibres (MF). They send axons to CA1 pyramidal cells via the Schaffer Collateral Pathway (SC), as well as to CA1 cells in the contralateral hippocampus via the Associational Commisural (AC) Pathway. CA1 neurons also receive inputs direct from the Perforant Path and send axons to the Subiculum (Sb). These neurons in turn send the main hippocampal output back to the EC, forming a loop.

40. Connections Afferents:  Much of cortex is reciprocally connected to entorhinal cortex 内嗅皮质  Cholinergic and GABA input via septal nuclei 隔核  Amygdala  VTA 中脑腹侧被盖区, LC 蓝斑, Raphe n. 中缝核 Efferents  Via the fornix 穹隆  Precommissural: septal nuclei  Post-commisural: mammillary bodies (to anterior thalamic nucleus via mammillothalamic tract)

41. Two limbic Axis Hippocampal Hippocampal Extroceptive 外感受 Extroceptive 外感受 Cognitive processes- learning and memory 认知 Cognitive processes- learning and memory 认知 Receive information from cortical sensory areas Receive information from cortical sensory areas Project to ant. Thalamus Project to ant. Thalamus Ant. Thalamus-cingulate gyrus-hippocampus (Papez circuit) Ant. Thalamus-cingulate gyrus-hippocampus (Papez circuit) Hippocampus-mammillary body-thalamus Hippocampus-mammillary body-thalamus Project to basal ganglion Project to basal ganglion Project to mid brain via medial forebrain bundle. Project to mid brain via medial forebrain bundle. Amygdaloid Amygdaloid Introceptive 内感受 Introceptive 内感受 Generation of emotions, motivational states 情感，动机 Generation of emotions, motivational states 情感，动机 Cortical sensory areas and internal organs Cortical sensory areas and internal organs Dorso medial thalamus Dorso medial thalamus Dorso medial thalamus- prefrontal cortex-amygdala. Dorso medial thalamus- prefrontal cortex-amygdala. Amygdala –ventro medial hypothalamus Amygdala –ventro medial hypothalamus Project to basal ganglion. Project to basal ganglion. Project to mid brain via medial forebrain bundle. Project to mid brain via medial forebrain bundle.

43. Part 3. Hypothalamus

44. Limbic system and hypothalamus

45. Hypothalamus 下丘脑

46. Embryological Development of the Anterior and Posterior Pituitary

47. Peptidergic neuroendocrine cells: Magnocellular neurons “Large” neurons “Large” neurons Located in paraventricular and supraoptic nuclei Located in paraventricular and supraoptic nuclei Secrete oxytocin and vasopressin into general circulation via posterior pituitary Secrete oxytocin and vasopressin into general circulation via posterior pituitary Oxytocin uterine contraction & milk ejection Oxytocin uterine contraction & milk ejection Vasopressin vasoconstriction, water resorption by the kidney Vasopressin vasoconstriction, water resorption by the kidney

49. “small” neurons “small” neurons Located in medial basal region, arcuate and tuberal nuclei, periventricular region, preoptic and paraventricular nuclei Located in medial basal region, arcuate and tuberal nuclei, periventricular region, preoptic and paraventricular nuclei Secrete releasing and inhibiting hormones into portal vasculature via anterior pituitary Secrete releasing and inhibiting hormones into portal vasculature via anterior pituitary Nobel prize awarded to Guillemin (Salk), Schally and Yalow in 1977 for their (independent) work in proving the hypothesis that the hypothalamus releases hormones that regulate the pituitary Nobel prize awarded to Guillemin (Salk), Schally and Yalow in 1977 for their (independent) work in proving the hypothesis that the hypothalamus releases hormones that regulate the pituitary Peptidergic neuroendocrine cells: Parvocellular neurons

52. Portal veins of hypophysis

56. Hypothalamus pathways Afferent Pathway Projecting from Median forebrain bundle Collaterals from other tracts Fornix Hippocampus (to MB) Stria terminalis amygdala Efferent Pathway Projecting to hypothalamicohypophyseal (from supraoptic nuclei) Neurohypophysis (pituitary) Mammillothalamic tract Anterior thalamic nucleus Widespread projections to many brain regions, including the cerebral cortex, via histamine and hypocretin containing neurons in the tuberal region of the hypothalamus

57. Part 4. Cingulate gyus and Parahippocampal gyrus

60. 思考题 简述边缘系统的研究历史 简述边缘系统的研究历史 边缘系统包括哪些结构？核心结构是什么？ 边缘系统包括哪些结构？核心结构是什么？ 试述杏仁核的位置、核团分部、纤维联系及功能。 试述杏仁核的位置、核团分部、纤维联系及功能。 试述海马的位置、分区、细胞构筑、内部通路及 外部纤维联系。 试述海马的位置、分区、细胞构筑、内部通路及 外部纤维联系。 试述下丘脑的位置及其与神经内分泌的关系。 试述下丘脑的位置及其与神经内分泌的关系。

61. Thanks !