心? 情緒? 神經生物學基礎? NH 3 Fragrance: Fried chicken Perfume Olfactory nerve Optic nerve? Motor pathways Emotional responses Cochlear nerve Limbic 1
Functions of Limbic system Memory Emotions-related responses Limbic 2
Amygdaloid body (amygdala) Hippocampal formation Hippocampus Parahippocampal gyrus Dentate gyrus Septal area / Basal forebrain Hypothalamus (Limbic) cortex: Cingulate gyrus, Orbital (Orbiotfrontal) cortex, Prefrontal cortex, Insula Anterior thalamus Limbic system Limbic 3
Amygdaloid Body (Amygdala, AMG) Position: between anterior end of temporal horn of the lateral ventricle and the ventral surface of lentiform nucleus Limbic 4
Olfactory nerve Limbic 5
Temporal lobe Olfactory nerve Limbic Olfactory pathway 6
Olfactory pathway and AMG Amygdala (AMG) Limbic 7
AMYGDALA: division / nuclei Dorsal (corticomedial nuclei) Ventrolateral (central nuclei / basolateral nuclei) Limbic 8
Dorsal (Corticomedial, Cortical) nuclei of AMG blending with uncus with afferents from olfactory bulb (lateral olfactory area) Olfactory bulb and cortex AMG (Corticomedial) Hypothalamus Limbic 9
Ventrolateral (central and basolateral nuclei) of AMG Both nuclei are a part of limbic system. Central nuclei: with corticomedial nu Basolateral nuclei: reciprocal connections with limbic cortex (prefrontal, temporal lobes and cingulate gyrus); thalamus and brainstem: medio-dorsal (dorsomedial) nuclei of thalamus, catecholamine nu, raphe nu, parabrachial nu of reticular formation; septal area and anterior hypothalamus (stria terminalis) Limbic 10
Interconnections of AMG Cortex temporal, insular, prefrontal, occipital Co-AMG AMG-Co Sensory: somatic, visceral, auditory etc VentroLat-AMG CM-AMG Thalamus (Medio-dorsal) Hypothalamus Brainstem Limbic 11
Major pathways for amygdala Afferent to AMG Stria terminalis To and from brainstem for regulations of autonomic responses etc. Ventral amygdalofugal pathways via Diagonal band of Broca Medial forebrain bundle Efferent to AMG Limbic 12
Stria terminalis: septal area --- AMG Fornix Limbic 13
Stria terminalis Th Limbic 14
Limbic Stria terminalis 15
Ventral amygdalofugal pathway (1) Limbic 16
Ventral amygdalofugal pathway (2) Emotionally driven activities also with some afferents Amygdala Hippocampus Limbic cortex Thalamus Dorsomedial nu. Ventral striatum Ventral pallidum Hypothalamus Brainstem Limbic 17
Diagonal band of Broca in anterior perforated substance (orbital cortex, behind olfactory tract, with passage of vessels) connections between amygdala and septal area Limbic 18
Medial forebrain bundle a collective term for fibers passing the ventral (basal) surface of the brain contains heterogeneous fiber tracts for different destinations important tracts for ascending and descending interconnections between septal area, hypothalamus and brainstem Limbic 19
Median forebrain bundle Limbic 20
Medial forebrain bundle Limbic 21
AMG and autonomic nervous system AMG Stria terminalis Septal area / Anterior hypothalamus Stria medullaris (thalami) Habenular nu. of dorsal thalamus Fasciculus retroflexus Interpeduncular nu. of midbrain Dorsal longitudinal fasciculus Hypothalamospinal fibers Limbic 22
Stria medullaris (thalami) Limbic 23
Limbic Stria Medullaris Thalami 24
Limbic 25
Functions of Amygdala Related to emotional feelings Fear Anger Methods of study Electrical stimulation Functional magnetic resonance imaging (fmri) Destructive lesions in temporal lobes Kluver-Bucy Syndrome: docility, loss of ability to learn, and abnormal sexual activity Limbic 26
Olfactory system and Amygdala Limbic 27
Fear perception and response Visual perception Amygdala Neocortex: fear sensations / recognition Autonomic system: (unconscious) responses Conditional reflex, Memory Limbic 28
Limbic 29
Organization Summary: amygdala corticomedial (olfactory) ventrolateral (limbic) Connections cortex (limbic: prefrontal, temporal, cingulate) thalamus (medio-dorsal)/brainstem (catechoaminergic) other limbic structures: septal area, hypothalmus Pathways Stria terminalis Medial forebrain bundle Ventral amygdalofugal pathway Limbic 30
Hippocampus Medial (mesial) surface of temporal lobe Anterior-posterior extension Limbic 31
Hippocampus Medial surface of temporal lobe Beneath lateral ventricle Limbic 32
Hippocampus Limbic 33
Structure of hippocampus Dentate gyrus Hippocampus (proper), cornu ammonis Parahippocampus gyrus Subiculum Subiculum Dentate gyrus Hippocampus uncus Limbic 34
Hippocampus: Alveus Myelinated axons (leaving & entering hippocampus) on ventricular surfaces of hippocampus; Forming the fimbria of hippocampus continuous with crus of fornix Limbic 35
Hippocampus
Organization of Hippocampus: 3 layers Molecular layer Pyramidal cell layer Polymorphic layer parahippocampal gyrus: neocortex, with 6 layers Limbic 37
Organization of Hippocampus: CA 1-3 CA (Cornus ammonis); CA1: Sommer s sector Limbic 38
Molecular layer of Hippocampus with axons and dendrites continuous with molecular layers of dentate gyrus and neocortex Limbic 39
Pyramidal cell layer of Hippocampus Large neurons: pyramidal cells Principal cells of hippocampus; With dendrites into Molecular layer; Axons through alveus & fimbria to fornix Limbic 40
Schaffer collateral Schaffer collaterals: branches of axons of pyramidal cells; passing polymorphic and pyramidal cell layers to synapse with dendrites of other pyramidal neurons Limbic 41
Pyramidal cell layer of hippocampus pyramidal neurons of CA1: sensitive to oxygen deprivation Temporal sclerosis Alzheimer disease continuous with layer 5 (internal pyramidal) of neocortex Limbic 42
Polymorphic cell layer of hippocampus Beneath alveus, With axons, dendrites and interneurons; Equivalent to layer 6 of neocortex Limbic 43
Organization of Dentate gyrus: 3 layers Molecular layer Granule cell layer: principal cells Polymorphic layer: Polymorphic layer of dentate gyrus: contineous with that of CA3 Limbic 44
Efferent fibers of Dentate gyrus Mossy fibers Traveling in hilus & polymorphic layer; giving branches to synapse with pyramidal cells of CA2 and CA3 Roles for memory: long-term potentiation Limbic 45
Hippocampus: Intrinsic connections Limbic 46
Long-Term Potentiation (LTP) present in Schaffer collaterals and mossy fibers of hippocampus increase in synaptic efficiency following highfrequency activity of a pre-synaptic terminals as molecular and cellular mechanism nderlying long-term memory Limbic 47
Afferents to Hippocampus Limbic 48
The largest afferents of hippocampal formation Perforant path Alvear path Entorhinal area: a part of lateral olfactory area and a gate for other cortical areas; receiving association fibers of temporal lobe and other neocortex Entorhinal afferents Limbic 49
Alvear path through subcortical white matter and alveus to end in hippocampus Fornix and fimbria afferents: from contralateral hippocampus, from septal areas, basal forebrain cholinergic neurons (substantia inominata) Limbic 50
Perforant path axons from entorhinal area through subiculum & base of hippocampus to end in dentate gyrus Limbic 51
Hippocampal efferents Limbic 52
Fornix: the largest hippocampal efferents Origin: hippocampus & parahippocampal gyrus Fimbria Crus: posterior limit of hippocampus Body: in contact of splenium (dorsal hippocampal commissure) Column: above the 3 rd ventricle; in front of interventricular foramen Limbic 53
Column of Fornix pre-commisural protion of fornix: above anterior commissure; giving fibers to septal area, anterior hypothalamus, substantia inominata post-commissural portion of fornix: fibers to lateral dorsal thalamic nuclei, hypothalamus (mamillary body via mammilothalamic fasciculus to ant. nu of Th, ventromedial nucleus) Limbic 54
Fornix Limbic 55
Fornix Limbic 56
Limbic 57
Mammillothalamic fasciculus (MTf) Origin: mamillary body Terminals: anterior nuclei of thalamus Anterior and lateral dorsal thalamic nucleus having reciprocal Th. communications with cingulate gyrus, which MTf also has reciprocal communication with parahippocampus gyrus Mam. Body Cingulum Parahippo. Limbic 58
Mamillo-thalamic fasciculus Limbic 59
Mamillo-thalamic (Mamillothalamic) fasciculus / tract Damaged in Korsakoff syndrome (alcoholic dementia) Amenesia Confabulation Apathy Lack of insight http://www.youtube.com/watch?v=wdcybxjaznm http://www.youtube.com/watch?v=ubslltsjfuy Limbic 60
Hippocampal function & dysfunction: memory and memory disorders Types of memory Explicit (Declarative) memory: knowledge mainly verbal, language, mathematic contents etc Implicit memory: learned skills, procedures, emotions associated structures: cerebellum, basal ganglia etc Limbic 61
Declarative Memory Steps of memory Immediate recall; Recent memory Memory consolidation; Long-term memory Information retrieving Factors: enhancing, interfering, emotional etc Role of hippocampus in memory Retention of short-term memory and its Transfer to long-term declarative memory Limbic 62
Hippocampus and Memory: Cellular mechanism Long-term potentiation (LTP) a postulated mechanism for storage of recent memory requiring for permanent memory new protein synthesis new synapse formation Limbic 63
Role of hippocampus in learning learning and memory : impaired in mice with defective functions of neurotransmitters in hippocampus Limbic 64
Clinical Note of Hippocampus: Alzheimer disease Pathophysiology: cholinergic hypothesis loss of cholinergic neurons in basal forebrain projecting to limbic system (particularly hippocampus) degeneration in entorhinal cortex, and hippocampus Essential role of hippocampus: bilateral hippocampal lesions lead to memory loss, particularly recent memory Limbic 65
The story of H.M. Intractable seizure Temporal lobectomy, partial Consequences Seizure: under control Blunt emotions Loss of memory Limbic 66
H.M. Limbic 67
What happens to H.M.? (How to improve memory for exam? 臨陣磨槍!) Hippocampus Cortex Memory consolidation / Information retrieval RAM Disk (macro) Limbic 68
Case history 住台北的一位退休公務員 3/13: 上午與太太搭高鐵南下高雄, 中午參加一位老朋友的喪禮, 晚上到台南, 夜宿嫁到台南的女兒家 3/14: 清晨醒來, 問 : 為什麼在這裡? 對於昨天 (3/13) 參加喪禮的事, 一概否認, 不記得有到高雄參加喪禮的事 一整天, 一直 ㄏㄨㄟ 個不停 3/15: 早上離開台南, 中午回到台北, 一切恢復正常, 但對於 3/12 晚間開始到 3/14 之間的事, 完全沒有記憶 What is your diagnosis? 中邪? Limbic 69
Transient Global Amnesia (TGA) a transient loss of memory, mainly recent events with Normal intellectual functions Intact (1) immediate recall and (2) remote memory Duration: usually resolve within 24 h Etiology and mechanisms: unknown, with transient lesions (mainly vascular insufficiency) in the hippocampus Limbic 70
Transient global amnesia Limbic 71
Hippocampus and Cerebral cortex Cortex Entorhinal cortex Perforant pathway Subiculum CA1 CA3 Dentate gyrus Schaffer collaterals Mossy fibers Limbic 72
睡醒後就失憶 : 她, 天天重新做人 (2010.06.12 自由時報 ) 編譯羅彥傑/ 綜合報導 英國一名四十七歲的已婚婦女, 因兩次車禍導致腦部受損, 喪失自從一九九四年以來的短期記憶, 此後每天醒來都是同一天, 也讓丈夫每天都得說服她相信兩人是夫妻, 頗類似好萊塢愛情喜劇 50 First Dates ( 我的失憶女友 ) 劇情 英國 每日郵報 十一日報導說, 住在英格蘭林肯郡斯波耳丁市的米歇兒. 菲波茲每天一覺醒來, 枕邊人都得說服她, 兩人是夫妻 當她表現懷疑時, 菲波茲先生就去拿相簿, 給她看兩人在一九九七年 ( 十三年前 ) 的結婚照 米歇兒在一九八五年與一九九 年先後發生機車與汽車車禍, 造成腦部受損 她的記憶最遠可追溯到一九九四年, 但此後任何一天發生的事情, 隔天就全忘光 這種情況令人聯想到二 四年電影 我的失憶女友, 劇中男主角亞當山德勒嘗試追求女主角茱兒芭莉摩, 但後者在車禍後就喪失每天日常生活的記憶 Limbic 73
睡醒後就失憶 : 她, 天天重新做人 (2010.06.12 自由時報 ) 米歇兒得使用數以百計的便利貼及手機日曆的記事提醒功能, 幫助自己記得每天的行程與要做的事 她做過的事或見過的人, 都必須記錄下來, 以便日後參考用 當她偶爾離家出外遊玩時, 還必須攜帶輸入住家地址的衛星導航系統 劍橋大學神經科學家耐斯特說, 米歇兒罹患的是罕見的順向失憶症 ( 或前行性失憶症 ) 不過, 這對她也有一些好處, 譬如沒有電視節目重播的困擾, 每一則笑話也都很好笑, 因為每次都是第一次聽到 她目前擔任慈善團體志工, 每週有三天照顧殘障人士 Limbic 74
Review: Hippocampus Organization Hippocampus Dentate gyrus Synaptic pathways Schaffer collaterals Mossy fibers Major afferents and efferents Alvear path Perforant path Fornix Limbic 75