1. Limbic System
Won Taek Lee, M.D., Ph.D.

2. Affective
Behavior
Emotion
Joy
and
Despair

3. Introduction Concept of Limbic System
Broca (1877) - ‘La Grand Lobe Limbique’
Papez (1937) - ‘Limbic Circuit’ - emotion
MacLean (1952) - ‘Limbic System’ - visceral brain
Nauta (1972) - ‘Septo-hypothalamo-mesencephalic continuum’

4. PAUL BROCA ( )
JAMES PAPEZ ( )

5. Limbic System - term of Paul MacLean (1952) - Visceral Brain
- triune concept of brain evolution
Hypothalamus
Nucleus accumbens
amygdaloid nuclear complex
orbitofrontal cortex
Some psychiatric implications on
physiological studies on fronto-
temporal portions of limbic system
(visceral brain). Electroencephalogr
Clin Neurophysiol 4: , 1952
Paul D. MacLean (1913- )

6. Septo-(Preoptico)-Hypothalamo- Mesencephalic Continuum
Main Components of Limbic System
Olfactory
Cortex
Septo-(Preoptico)-Hypothalamo- Mesencephalic Continuum
Spinal
Cord
&
Brain
Stem
Hippocampal
Formation
Septal
Region
Hypothalamus
Limbic
Midbrain
Area
Amygdaloid
Nuclear
Complex
Limbic System

7. Expression
of Emotion
Septo-
hypothalamo-
mesencephalic
continuum

8. Components of the Limbic System (I)
TELENCEPHALON
Limbic Lobe
Gyrus Fornicatus
Cingulate Gyrus
Parahippocampal Gyrus
Hippocampal Formation
Hippocampus
Dentate Gyrus
Subiculum
Hippocampal Rudiments
Fasciolar Gyrus
Indusium Griseum
Olfactory Cortex (Rhinencephalon)
- Piriform Lobe
Prepiriform Cortex
Periamygdaloid Cortex
Entorhinal Cortex
Basal Forebrain Area
Substantia Innominata
Basal Nucleus of Meynert
Ventral Pallidum
Nucleus Accumbens (Septi)
Septal Region
Septal Area
Paraterminal Gyrus
Subcallosal Gyrus
Septal Nuclei
Dorsal, Lateral and Medial
Nucleus of Diagonal Band of Broca
Bed Nucleus of Stria Terminalis
Amygdaloid Nuclear Complex
Corticomedial Nuclear Group
Basolateral Nuclear Group
Central Nucleus

9. Components of the Limbic System (II)
DIENCEPHALON
Thalamus, Limbic
Anterior Nuclear Group
Mediodorsal (MD) Nucleus
Midline Nuclei
Hypothalamus
Preoptic Region
Preoptic Periventricular Nucleus
Medial Preoptic Nucleus
Supraoptic Region
Suprachiasmatic Nucleus
Anterior Nucleus
Supraoptic Nucleus
Paraventricular Nucleus
Tuberal Region
Dorsomedial Nucleus
Ventromedial Nucleus
Infundibular (Arcuate) Nucleus
Mammillary Region
Lateral, Medial and Intermediate
Mammillary Nucleus
Posterior Nucleus
Epithalamus
Habenular Nucleus
Medial Habenular Nucleus
Lateral Habenular Nucleus
Pineal Gland
MESENCEPHALON
Limbic Midbrain Area
Median Raphe Nucleus
Dorsal Raphe Nucleus
Ventral Tegmental Area
Dorsal Tegmental Nucleus
Periaqueductal Gray

10. Components of the Limbic System

11. Limbic Lobe Limbic Lobe Classification of Cortex Gyrus Fornicatus
Cingulate Gyrus
Parahippocampal Gyrus
Entorhinal Area
Isthmus
Hippocampal Formation
Hippocampus Proper
(Ammon’s horn)
Dentate Gyrus
Subiculum
Hippocampal Rudiments
Fasciolar Gyrus
Indusium Griseum
Classification of Cortex
Isocortex - Neocortex
Allocortex
Archicortex
Hippocampus
Dentate Gyrus
Paleocortex
Olfactory Bulb
Piriform Lobe
Mesocortex (Juxtallocortex,
Periallocortex, Mesallocortex)
Cingulate Gyrus

12. Hippocampal Formation
Hippocampus Proper
(Ammon’s horn,
Cornu Ammonis)
Dentate Gyrus
Subiculum

13. Hippocampal Formation
1. uncus
2. dentate gyrus
3. fornix
4. corpus callosum
5. fasciolar gyrus
6. hippocampal sulcus
7. parahippocampal
gyrus
8. collateral sulcus

14. Hippocampal Formation (Lateral View)

15. Hippocampal Formation (Medial View)

16. Hippocampal Formation (Medial View)

17. Hippocampal Formation - Archicortex
Archicortex - 3 layers
Hippocampus Proper
Molecular Layer
Pyramidal Layer
Polymorphic Layer
Dentate Gyrus
Granular Layer
Subiculum
Transitional type between hippocampal archicortex and entorhinal paleocortex

18. Classification of Cortex
Isocortex
6 layered cortex
homotypical and
heterotypical isocortex
Allocortex
Paleocortex
olfactory cortex
- piriform lobe
Archicortex
3 layered cortex
- hippocampal formation

19. Archicortex - lamination by Ramon y Cajal
7. stratum
moleculare
6. stratum
lacunosum
5. stratum
radiatum
4. stratum
pyramidalis
3. stratum oriens
2. Alveus
1. ependyma

20. Hippocampus

21. Ammon’s horn
(Cornu Ammonis)

22. Subdivision of Cornu Ammonis (Hippocampus proper)
- by differences in cell morphology,
relative development and connections
- subdivision by Lorente de Nó (1934)
CA1
CA2
CA3
CA4 - Area Dentata
Fascia Dentata: outer 2 layers
of area dentata
Rafael Lorente de Nó

23. Hippocampal Formation
Dentate gyrus, CA1, CA2, CA3, CA4, subiculum

24. Division of Hippocampal Formation
4. Fascia dentata
3. CA4
2. CA3, CA2
1. CA1
6. Subiculum
20. Presubiculum
21. Parasubiculum
22. Entorhinal cortex

25. Development of the Hippocampus
1. dentate gyrus 2. hippocampus proper 3. subiculum
HS: hippocampal sulcus TH: temporal horn

26. Hippocampal Formation
Hippocampus Proper
CA1
CA2
CA3
CA4 - Area Dentata
Dentate Gyrus
Subiculum
Prosubiculum
Presubiculum
Parasubiculum

27. Connections of Hippocampal Formation
1. Intrinsic Connections
classic trisynaptic pathway
2. Afferent Connections
perforant and alveolar path
3. Efferent Connections
fornix

28. Intrinsic Connections
Classic Trisynaptic Pathway
1. Entorhinal cortex (perforant path)
 dentate gyrus granular cell
2. Granular cell axon (mossy fiber)
 CA3 pyramidal cell
3. Pyramidal cell (Schaffer collateral)
 CA1 pyramidal cell
 subiculum  entorhinal cortex

29. Afferent Connections of
CA1 Pyramidal Neuron
stratum moleculare
- entorhinal cortex (perforant path)
stratum lacunosum
- Schaffer collateral from CA3
stratum radiatum
- commissural axon
- mossy fibers from dentate gyrus
stratum pyramidale
- basket cell
stratum oriens
- short axon cell

30. Afferent Connections From Entorhinal Cortex Alveolar Path
from medial part of EC
to CA1 and Subiculum
Perforant Path
from lateral part of EC
to CA1, CA2, CA3 and
Dentate Gyrus

31. Entorhinal Cortex 1. entorhinal cortex 2. uncus 3. fornix
4. dentate gyrus
5. hippocampal sulcus
6. collateral sulcus

32. Afferent Connections EC & Hippocampal Afferents Surrounding Neocortex
from association areas
- temporal, frontal lobe
Limbic System
from hypothalamus,
amygdala, septal area,
anterior thalamic nuclei,
and midbrain limbic area

33. Efferent Connections FORNIX Alveus Fimbriae Crus Commissure Corpus
Column

34. Efferent Connections Fornix Postcommissural Fornix – main bundle
- from pyramidal neurons of hippocampus & subiculum
- 1.2 million fibers in humans
Postcommissural Fornix – main bundle
to Mammillary Body
Anterior Thalamus
Lateral Septal Nuclei
Hypothalamus
Midbrain Tegmentum

35. Efferent Connections Precommissural Fornix – smaller less compact
- mostly originated from the hippocampus proper
to Septal Nuclei
Lateral Preoptic Area
Anterior Hypothalamic Area
Nucleus of Diagonal Band of Broca
Nucleus Accumbens Septi
Medial Surface of Frontal Lobe
Caudate Nucleus and Putamen
Amygdala and Claustrum

36. Summary of Hippocampal Connections
Afferent Connections
Entorhinal Cortex
Alveolar Path
from medial part of EC
to CA1 and Subiculum
Perforant Path
from lateral part of EC
to CA1, CA2, CA3 and
Dentate Gyrus
Mossy fiber - CA3
- Schaefer fiber (CA3-CA1)
Others
Hypothalamus, Septal Nuclei,
Substantia Innominata
Midbrain Limbic Area
Efferent Connections
FORNIX
from Pyramidal Neurons of
hippocampus & subiculum
Alveus, Fimbriae, Crus
Commissure, Corpus, Column
Precommissural Fornix
to Septal Nuclei,
Nucleus Accumbens Septi
Anterior Hypothalamic Area
Medial Surface of Frontal Lobe
Anterior Olfactory Nucleus
Postcommissural Fornix
to Mammillary Body
Anterior Thalamus
Hypothalamus
Bed Nucleus of Stria Terminalis

37. Dopamine hypothesis of Schizophrenia
Hypersensitive
dopamine receptors
in limbic cortex
21st century
schizoid man

38. Septal Region Septal Region Septal Area Septal Nuclei Connections
Paraterminal (Subcallosal) Gyrus
Subcallosal Area (Parolfactory Area)
Septal Nuclei
Dorsal Septal Nucleus
Lateral septal Nucleus
Medial Septal Nucleus (Ch1)
Nucleus of Diagonal Band
of Broca (Ch2, Ch3)
Bed Nucleus of Stria Terminalis
Bed Nucleus of
Anterior Commissure
Septum
Septum pellucidum
Septum Verum
- Septal Nuclei
Connections
Stria Medullaris Thalami
to medial habenular nucleus
Medial Forebrain Bundle
to hypothalamus and midbrain
Fornix - to hippocampus
Stria Terminalis & Diagonal Band
from amygdaloid complex

39. Basal Forebrain Area and Limbic Basal Ganglia
- structures deep to the
anterior perforating substance
Olfactory Tubercle
Substantia Innominata
Basal Nucleus of Meynert (Ch4)
cf. Alzheimer’s disease
Ventral Pallidum
- non cholinergic portions
of the substantia innominata
- part of limbic basal ganglia
Limbic Basal Ganglia
Nucleus Accumbens Septi
(Ventral Striatum)
afferents from
hippocampal formation
amygdaloid body
cingulate gyrus
ventral tegmental area
dorsal raphe nucleus
efferents to ventral pallidum
Ventral Pallidum
efferents to
mediodorsal (MD) thalamus
substantia nigra
subthalamic nucleus
amygdaloid nucleus
lateral habenular nucleus

40. Theodor Meynert (1833-1892) Austrian Neurologist
Professor of Neurology and
Psychiatry in Wien University
Teacher of Sigmund Freud
Use serial sections in histology
of nervous system
Basal Nucleus of Meynert
in substantia innominata
Dorsal tegmental decussation
of Meynert

41. BASAL FOREBRAIN AREA (Heimer)
Basal Forebrain Area Components
BASAL FOREBRAIN AREA (Heimer)
Ventral Striatum, Part of
Ventral Pallidum
Basal Nucleus of Meynert (Ch4)
Extended Amygdala
cf. Cholinergic Cell Groups (Mesulam)
(Magnocellular Basomedial Telencephalic Complex )
1. Ch1 (Medial Septal Nucleus)
2. Ch2 (Nucleus of Diagonal Band of Broca)
3. Ch3 (Nucleus of Diagonal Band of Broca)
4. Ch4 (Basal Nucleus of Meynert)
5. Ch5 (Pedunculopontine Tegmental Nucleus)

42. Amygdaloid Nuclear Complex
Connections
Corticomedial Nuclear Group
Olfactory Pathway
via Lateral Olfactory Stria
Basolateral Nuclear Group
from Sensory Association Area
Central Nucleus
from brain stem visceral
afferent nuclei
Stria Terminalis
to bed nucleus of stria terminalis
hypothalamus, epithalamus
amygdaloid body
Ventral Amygdalofugal Pathway
to septal nuclei, hypothalamus
thalamus (MD) and
midbrain limbic area
Amygdaloid Nuclear Complex
Corticomedial Nuclear Group
Anterior Amygdaloid Area
Cortical Amygdaloid Nucleus
(Periamygdaloid Cortex)
Medial Amygdaloid Nucleus
Lateral Olfactory Nucleus
(Lateral Olfactory Gyrus)
Basolateral Nuclear Group
Lateral Nucleus
Basal Nucleus
Accessory Basal Nucleus
Central Nucleus

43. Amygdala
L. almond
K. F. Burdach’s
term

44. Connections of the Amygdala

45. Extended Amygdala Extended Amygdala Connections
Central Amygdaloid Nucleus
Medial Amygdaloid Nucleus
Bed Nucleus of
Stria Terminalis (BST)
- bridging cell groups directly
interconnects amygdaloid
and bed nucleus of stria
terminalis (BST)
which refered to as
Extended amygdala.
Connections
Afferents from
Intra-amygdaloid association
fibers from basolateral
amygdaloid nucleus,
whic recieves wealth of
modality-specific and
multimodal sensory input
from the cerebral cortex.
Efferents to
Hypothalamus and
Brain Stem

46. Amygdaloid Nuclear Complex Extended Amygdala
A. bed nucleus of
stria terminalis
B. centromedial amygdala
C. basolateral amygdala
D. cortical amygdala
E. connections between
extended amygdala
and amygdala:
sublenticular portion of
substantia innominata
1. stria terminalis

47. Amygdaloid Nuclear Complex
Emotion
& Amygdala

48. Autism
Dysfunction of
amygdala
Mercury
Rising

49. Limbic Thalamus Thalamus, Limbic Connections Anterior Nuclear Group
Anteroventral Nucleus (AV)
Anterodorsal Nucleus (AD)
Anteromedial Nucleus (AM)
Lateral Dorsal (LD) Nucleus
Mediodorsal (MD) Nucleus
Pars magnocellularis (MDmc)
Pars parvocellularis (MDpc)
Pars paralaminaris (MDpl)
Pars densocellularis (MDdc)
Midline Nuclei
Paratenial Nucleus (Pt)
Reunience Nucleus (MV)
Submedial Nucleus (Sm)
Rhomboid Nucleus (Rh)
Connections
Anterior Nuclear Group
from mammillary body,
hippocampal formation,
cingulate gyrus
to cingulate gyrus
subiculum
MDmc
from primary olfactory cortex,
ventral pallidum
to orbitofrontal cortex
MDpc, MDpl, MDdc
from substantia nigra
limbic midbrain area
to medial frontal cortex
frontal eye field (area 8)

50. Connections of the Limbic Thalamus
Orbitofrontal
Cortex
cingulate
gyrus
Frontal
Eye Field
Medial
Frontal
Gyrus
Primary
Orbitory
Cortex
MB, HF
SNr, SC, RF

51. Epithalamus Epithalamus Habenular Nucleus Pineal Gland Diencephalon
Medial Habenular Nucleus
Lateral Habenular Nucleus
Pineal Gland
Stria Terminalis
from septal nuclei,
hypothalamus,
anterior thalamic nucleus,
substantia innominata,
globus pallidus
Habenulointerpeduncular Tract
(Fasciculus Retroflexus)
from medial habenular nucleus
to interpeduncular nucleus
from lateral habenular nucleus
to midbrain limbic area
Diencephalon
Epithalamus
Hypothalamus
Thalamus (Dorsal Thalamus)
Subthalamus (Ventral Thalamus)

52. surrounding structures
Epithalamus and
surrounding structures

53. Hypothalamus Hypothalamic Nuclear Group Tuberal Region MEDIAL ZONE
Dorsomedial Nucleus
Ventromedial Nucleus
Infundibular (Arcuate) Nucleus
Mammillary Region
Lateral Mammillary Nucleus
Medial Mammillary Nucleus
Intermediate Mammillary
Nucleus
Posterior Nucleus
LATERAL ZONE
Lateral Hypothalamic Nucleus
Lateral Tuberal Nucleus
Hypothalamic Nuclear Group
MEDIAL ZONE
Preoptic Region
Preoptic Periventricular
Nucleus
Medial Preoptic Nucleus
Supraoptic Region
Suprachiasmatic Nucleus
Anterior Nucleus
Supraoptic Nucleus
Paraventricular Nucleus

54. Hypothalamic Cell Group

55. Connections of the Hypothalamus
Major Afferent Connections
1. Ascending Visceral Fibers
via dorsal longitudinal
fasciculus (DLF) and
mammillary peduncle
from visceral afferent nuclei,
limbic midbrain area
2. Via Medial Forebrain Bundle
from Septum, Amygdala and
Paleocortex
3. Via Fornix
from Hippocampal Formation
Major Efferent Connections
1. Descending Visceral Fibers
via dorsal longitudinal
fasciculus (DLF) and
mammillary peduncle
to visceral efferent nuclei,
limbic midbrain area
2. Via Medial Forebrain Bundle
to Septum, Amygdala and
Paleocortex
3. Via Mammillothalamic Tract
to Anterior Thalamic Nuclei

56. Functional Aspects of Hypothalamus
1. Endocrine Function
Hormones of the Neurohypophysis - ADH, Oxytocin
(Supraoptic and Paraventricular Nucleus)
Releasing and Inhibiting Hormones (Tuberal region)
- Hypothalamo-hypophyseal Portal System
2. Visceral Function (Autonomic Center of CNS)
3. Limbic Function

57. Sham Rage - an affective attack expression - evoked by radio
stimulation of
medial hypothalamus
“Because the cat does not
direct its attack toward any
target, we regard this as
just a fragment of a normal
attack” (Delgado, 1981)

58. Silent Attack - little emotional expression - evoked by electric
stimulation of
perifornical nuc.
of hypothalamus
“The cat moves swiftly
and with little sign of
emotion to bite the
rat’s neck and kill it”
(Siegel & Brutus, 1990)

59. Anorexia
Nervosa
Karen Anne Carpenter
( )

60. Limbic Midbrain Area Limbic Midbrain Area
Median Raphe (Superior Central) Nucleus (B6, B8)
Dorsal Raphe Nucleus (B7)
Ventral Tegmental Area (VTA, A10)
Dorsal Tegmental Nucleus (Gudden)
Interpeduncular Nucleus
Periaqueductal Gray

61. Olfactory Cortex (Rhinencephalon)
Prepiriform Cortex - Area 51
Gyrus Ambiens
Lateral Olfactory Gyrus
(Lateral Olfactory Nucleus)
Periamygdaloid Cortex
Cortical Amygdaloid Nucleus
Entorhinal Area (Cortex) - Area 28

62. Olfactory System - Olfactory Pathways
Modality: Olfaction
Receptor: Olfactory Cell of Olfactory Epithelium
Cranial Nerve: I (Olfactory Nerve)
1st Neuron: Olfactory neuron --- Olfactory nerve (I)
2nd Neuron: Olfactory Bulb --- Mitral & Tufted Cell
olfactory tract
olfactory striae
lateral & intermediate olfactory striae
Termination: Primary Olfactory Area (Rhinencephalon)
piriform lobe (prepiriform cortex, entorhinal cortex)
corticomedial amygdala
anterior perforated substance (olfactory tubercle)

63. Olfactory System - Olfactory Pathways
A. olfactory epithelium
B. olfactory bulb
C. nucleus of diagonal band
of Broca
D. periamygdaloid cortex
E. cirticomedial amygdala
F. entorhinal area
G. septal nuclei
I. olfactory nerve
1. olfactory tract
2. lateral olfactory stria
3. intermediate olfactory stria
4. medial olfactory stria

64. Olfactory System - Connections of Primary Olfactory Cortex
A. olfactory epithelium
B. olfactory bulb
C. nucleus of diagonal band
of Broca
D. periamygdaloid cortex
E. cirticomedial amygdala
F. entorhinal area
G. mediodorsal thalamic
nucleus (MD)
I. olfactory nerve
1. olfactory tract
2. lateral olfactory stria
3. intermediate olfactory stria
4. thalamocortical radiation

65. Archicortex and Paleocortex
hedgehog
tupaia
(tree shrew)
lemur

66. Connections of the Limbic System

67. Septo-(Preoptico)-Hypothalamo- Mesencephalic Continuum
Olfactory
Cortex
Septo-(Preoptico)-Hypothalamo- Mesencephalic Continuum
Spinal
Cord
&
Brain
Stem
Hippocampal
Formation
Septal
Region
Hypo-
thalamus
Limbid
Midbrain
Area
Amygaloid
body
Limbic System

68. Papez Circuit Entorhinal Cortex (Area 28) Hippocampal Formation
alveolar path
perforant path
cingulum
Hippocampal
Formation
Cingulate
Gyrus
fornix
thalamocortical
radiation
Mammillary
Body
Anterior
Thalamic Nuclei
mammillothalamic tract

69. Papez Circuit A. Hippocampal Formation B. mammillary body
C. thalamic anterior nucleus
D. cingulate gyrus
1. fornix
2. mammillothalamic tract
3. thalamocortical radiation
4. cingulum

70. Functional Aspects of Limbic System
Limbic Function
Functional Aspects of Limbic System
1. Emotion - Affective Behavior
Amygdala
Limbic and Prefrontal Cotex
- Desire, Motivation, Goal-directed Behavior
Hypothalamus and Brain Stem
- ANS - maintenance of self (appetites)
maintenance of species (sexual function)
cf. Klüver-Bucy Syndrome
2. Memory and Learning
Papez Circuit
cf. Korsakoff’s syndrome

71. Behavioral changes of maintenance of self (appetites)

72. Behavioral changes of maintenance of self (aggression)
sham rage silent attack

73. Limbic Function Klüver-Bucy syndrome
 Monkey or cats with bilateral damage of temporal lobes
including amygdala and hippocampal formation
 Fail to display normal fear of anxiety (docility)
- attempt to pick up snakes and lighted matches
 Regression to oral stage
- put almost anything into mouth
 Marked increase in both the amount and diversity of
sexual activity

74. Klüver-Bucy syndrome in cats: Mating behavioral changes

75. Heinrich Klüver Paul Clancy Bucy
( ) ( )

76. Limbic Function
Cognitive and
Emotional
Processes

77. Evolution and Limbic System
Limbic Function
Evolution and Limbic System
- Triune Concept of MacLean
Protoreptilian Brain
(R Complex) ---- Instinct
Paleomammalian Brain
--- Limbic System ---- Emotion
Neomammalian Brain
--- Neocortex --- Analytical, Reasoning