2. Smells are surer than sounds and sights to make your heart-strings crack. - Rudyard Kipling

3. Olfactory system n Conveys specific visceral sensation (smell) via n. olfactorius. n Does not relay in the thalamus. n Connections with thalamus, hypothalamus, amygdaloid complex & hippocampal formation.

4. Structure of the olfactory system І. Receptor cells n Chemoreceptors. n Aboutо 25 billions on each side. n Located in the nasal mucosa. n Regenerate. n 1 st order neurons in the olfactory pathway. n Bipolar neurons, unmyelynated axons form nn. оlfactоrii. n In bulbus olfactorius the axons synapse with the mitral cells in olfactory glomerulus.

5. Nervi olfactorii

6. II. Bulbus olfactorius n On lamina cribrosa of os ethmoidale n Entered by olfactory nerves. n 6-layered structure. n 4 cell types: –periglomerular - inhibitory –tufted - efferent (ІІ order) –mitral - efferent (ІІ order) –granule - inhibitory n Glomerulus – polysynaptic structure, ensuring conversion of olfactory impulses on the mitral cells.

7. Bulbus olfactorius

8. Bulbus olfactorius -клетъчен състав

9. Synaptic organization of bulbus olfactorius Dendrodendrite synapses Glutamate (excitory) GABA (inhibitory)

10. Types of synapses Lateral inhibition.

11. ІІІ. Tractus olfactorius: –in sulcus olfactorius. –Axons of mitral and tufted cells. –nucl. olfactorius anterior (modulator): –terminates in trigonum olfactorium. ІV. Stria olfactoria lateralis –to primary olfactory cortex through limen insulae V. Stria olfactoria medialis –to area subcalosa and gyrus paraterminalis

12. Tractus olfactorius

13. VІ. Olfactory corex n Primary –on uncus (area 34 after Brodmann). –fibers from stria olfactoria lateralis. –contains prepiriform & periamygdaloid areas. –connectins with nucl. medialis dorsalis of thalamus, hypothalamus, hipocampal formation. n Secondary –entorhinal area of gyrus parahippocampalis (area 28). –Impulses from primary areas. –efferents to hippocampus. n Orbitofrontal cortex –Impulses from nucl. medialis dorsalis thalami –conscious preception of smell.

14. Olfactory corex

15. Orbitofrontal cortex We need our orbitofrontal cortex to make intelligent choices. Its individual cells code for value. Ann Thomson, Nature Neuroscience

16. Pathways in the olfactory system

17. Limbic system

18. n Morphological substrate of emotions and behaviour. n Role in emotional behavior, feeding, defensive reaction, sexual behaviour, memory and learning. n Functions mediated through hypothalamus and autonomic system. n Contains cortical & subcortical (nuclei) structures.

19. AffectivebehaviorEmotionHappinessandGrief

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

21. JAMES PAPEZ (1883-1958) PAUL BROCA (1824-1880)

22. Paul D. MacLean (1913- ) Limbic system - Term of Paul MacLean (1952) - Visceral brain -Triple concept of brain evolution of brain evolutionHypothalamus Nucleus accumbens Nucleus amygdaloideus Cortex orbitofrontalis Some psychiatric implications on physiological studies on fronto- temporal portions of limbic system (visceral brain). Electroencephalogr Clin Neurophysiol 4: 407-418, 1952

23. Septo-(Preoptico)-Hypothalamo- Mesencephalic Continuum Parts of the limbic system Area Areaseptalis septalis Hypothalamus Hypothalamus MidbrainMidbrain Hippocampal Hippocampalformation formation Olfactory Olfactorycortex cortex Amygdaloid Amygdaloidcomplex complex Spinalcord&Brainstem Limbic system

24. Expression of emotion Septo-hypothalamo-mesencephaliccontinuum

25. Parts of the limbic system TELENCEPHALON Lobus Limbicus Lobus Limbicus Gyrus Fornicatus Gyrus Fornicatus Gyrus Cingulatus Gyrus Cingulatus Gyrus Parahippocampalis Gyrus Parahippocampalis Hippocampal Formation Hippocampal Formation Hippocampus Hippocampus Gyrus Dentatus Gyrus Dentatus Subiculum Subiculum Hippocampal Rudiments Hippocampal Rudiments Gyrus Fasciolaris Gyrus Fasciolaris Indusium Griseum Indusium Griseum Cortex Olfactorius (Rhinencephalon) Cortex Olfactorius (Rhinencephalon) - Lobus Piriformis - Lobus Piriformis Cortex Prepiriformis Cortex Prepiriformis Cortex Periamygdaloideus Cortex Periamygdaloideus Cortex Entorhinalis Cortex Entorhinalis Basal forebrain Substantia Innominata Substantia Innominata Nucleus Basalis на Meynert Nucleus Basalis на Meynert Pallidum Ventralis Pallidum Ventralis Nucleus Accumbens (Septi) Nucleus Accumbens (Septi) Regio Septalis Area Septalis Area Septalis Gyrus Paraterminalis Gyrus Paraterminalis Gyrus Subcallosus Gyrus Subcallosus Nuclei Septalis Nuclei Septalis Dorsal, lateral and medial Dorsal, lateral and medial Nuclei Septalis Nuclei Septalis Nucleus Stria Diagonalis Broca Nucleus Stria Diagonalis Broca Nucleus Stria Terminalis Nucleus Stria Terminalis Corpus Amygdaloideum Pars Corticomedialis Pars Corticomedialis Pars Basolateralis Pars Basolateralis Nucleus Centralis Nucleus Centralis

26. Lobus Limbicus Lobus Limbicus Lobus Limbicus Gyrus Fornicatus Gyrus Fornicatus Gyrus Cinguli Gyrus Cinguli Gyrus Parahippocampalis Gyrus Parahippocampalis Area Entorhinalis Area Entorhinalis Isthmus Isthmus Hippocampal Formation Hippocampal Formation Hippocampus Proper Hippocampus Proper (Ammon’s horn) (Ammon’s horn) Gyrus Dentatus Gyrus Dentatus Subiculum Subiculum Hippocampal Rudiments Hippocampal Rudiments Gyrus Fasciolaris Gyrus Fasciolaris Indusium Griseum Indusium Griseum Класификация на кората Isocortex - Neocortex Isocortex - Neocortex Allocortex Allocortex Archicortex Archicortex Hippocampus Gyrus Dentatus Gyrus Dentatus Paleocortex Paleocortex Bulbus Olfactorius Bulbus Olfactorius Lobus Piriformis Lobus Piriformis Mesocortex (Juxtallocortex, Mesocortex (Juxtallocortex, Periallocortex, Mesallocortex) Periallocortex, Mesallocortex) GyrusCinguli Gyrus Cinguli

27. Parts of the limbic system

28. Limbic cortex n On medial aspect of the hemispheres n Archicortex –In some parts paleo- & neocortex. n External ring n Internal ring

29. Limbic cortex External ring External ring - gyrus cinguli - area subcallosa - gyrus parahippocampalis - uncus. Internal ring Internal ring - gyrus paraterminalis - indusium griseum - Hippocampal formation.

31. Hippocampus Proper (Ammon’s horn, (Ammon’s horn, Cornu Ammonis) Cornu Ammonis) Gyrus Dentatus Subiculum Hippocampal formation

32. Hippocampus – cortical fold in the lateral ventricle caused by sulcus hippocampi - 3-layered archicortex - stratum pyramidale - efferents, forming alveus and fimbria hippocampi - stratum moleculare - stratum radiatum - Subiculum (paleocortex) - affrents from hippocampus - efferents to corpora mamillaria and nucl. anterior thalami Parasubiculum (paleocortex) - transition to gyr. parahippocampalis

33. 1. uncus 2. gyrus dentatus 3. fornix 4. corpus callosum 5. gyrus fasciolaris 6. sulcus hippocampalis hippocampalis 7. gyrus parahippocampal parahippocampal 8. sulcus collateralis Hippocampal formation

34. Hippocampal formation ( lateral view )

35. Hippocampal formation (medial view)

36. Archicortex - 3 layers Archicortex - 3 layers Hippocampus Proper Hippocampus Proper Str. Moleculare Str. Moleculare Str. Pyramidale Str. Pyramidale Str. Polymorphe Str. Polymorphe Gyrus Dentatus Gyrus Dentatus Str. Moleculare Str. Moleculare Str. Granulare Str. Granulare Str. Polymorphe Str. Polymorphe Subiculum Subiculum Transient between hippocampal archicortex and entorhinal paleocortex Transient between hippocampal archicortex and entorhinal paleocortex Hippocampal formation - Archicortex

37. Classification of the cortex Isocortex Isocortex 6-layered cortex 6-layered cortex homotypical and homotypical and heterotypical heterotypical Allocortex Allocortex Paleocortex Paleocortex olfactory cortex olfactory cortex - lobus piriformis - lobus piriformis Archicortex Archicortex 3-layered 3-layered - hippocampal formation - hippocampal formation

38. Archicortex - after Ramon y Cajal 7. stratum moleculare moleculare 6. stratum lacunosum lacunosum 5. stratum radiatum radiatum 4. stratum pyramidalis pyramidalis 3. stratum oriens 2. alveus 1. ependyma

39. Hippocampus and memory Х.M. - пациент с антеградна и ретроградна амнезия, възникнала след мозъчна операция за лечение на епилептични припадъци.

41. Connection in the hippocampal formation 1. Internal connections trisynaptic pathway 2. Afferent connections perforant and alveolar pathway perforant and alveolar pathway 3. Efferent connctions fornix fornix

42. Internal connections Classical 3-neuron pathway 1. Енторинална кора (perforant pathway)  granule cell of gyrus dentatus  granule cell of gyrus dentatus 2. Granules cells (mossy fiber)  CA3 pyramid cells  CA3 pyramid cells 3. Pyramid cells (Schaffer collateral)  CA1 pyramid cells  CA1 pyramid cells  subiculum  cortex entorhinalis

43. Afferents From Cortex Entorhinalis Alveolar pathway Alveolar pathway from medial EC from medial EC to CA1 and Subiculum to CA1 and Subiculum Perforant pathway Perforant pathway from medial EC from medial EC to CA1, CA2, CA3 & to CA1, CA2, CA3 & Gyrus Dentatus Gyrus Dentatus

44. Efferents FORNIX Alveus Alveus Fimbriae Fimbriae Crus Crus Commissurа Commissurа Corpus Corpus Column Column

45. Efferents Fornix -from pyramid cells of hippocampus & subiculum -from pyramid cells of hippocampus & subiculum - 1.2 million fibers - 1.2 million fibers Postcommissiral Fornix – basic bundle Postcommissiral Fornix – basic bundle to Corpus Mammillare to Corpus Mammillare Thalamus Anterior Thalamus Anterior Nuclei Septi Lateralis Nuclei Septi Lateralis Hypothalamus Hypothalamus Tegmentum of midbrain Tegmentum of midbrain

46. Efferents Precommissural Fornix – smaller - mainly from hippocampus proper to Nuclei Septi to Nuclei Septi Area Preoptica Lateralis Area Hypothalamica Anterior Nucleus Striae Diagonalis Broca Nucleus Accumbens Nucleus Accumbens Medial aspect of frontal lobe Medial aspect of frontal lobe Nucleus Caudatus & Putamen Nucleus Caudatus & Putamen Amygdala & Claustrum

47. Efferent FORNIX FORNIX from pyramid cells from pyramid cells hippocampus & subiculum hippocampus & subiculum Alveus, Fimbriae, Crus Alveus, Fimbriae, Crus Commissure, Corpus, Column Commissure, Corpus, Column Precommissural Fornix Precommissural Fornix to Nuclei Septal, to Nuclei Septal, Nucleus Accumbens Nucleus Accumbens Area Hypothalamica Anterior Area Hypothalamica Anterior Nucleus Olfactorius Anterior Nucleus Olfactorius Anterior Postcommissural Fornix Postcommissural Fornix to Corpus Mammillare to Corpus Mammillare Thalamus Anterior Thalamus Anterior Hypothalamus Hypothalamus Nucleus Striaе Terminalis Nucleus Striaе TerminalisAfferent Entorhinal Cortex Entorhinal Cortex Alveolar pathway Alveolar pathway medial EC medial EC to CA1 and Subiculum to CA1 and Subiculum Perforant pathway Perforant pathway from lateral EC from lateral EC to CA1, CA2, CA3 and to CA1, CA2, CA3 and GyrusDentatus GyrusDentatus Gyrus Dentatuse Gyrus Dentatuse Mossy fiber - CA3 Mossy fiber - CA3 - Schaefer fiber (CA3-CA1) - Schaefer fiber (CA3-CA1) Others Others Hypothalamus, Nuclei Septi, Hypothalamus, Nuclei Septi, Substantia Innominata Substantia Innominata Midbrain Midbrain Summary of connections

48. Subcortical limbic structures 1. Amygdaloid complex 2. Mammillary body 3. Septal area 4. Nucleus anterior, nucleus medialis dorsalis & nuclei intralaminares thalami 5. Nucleus accumbems 6. Substantia innominata 7. Nuclei habenulae 8. Hypothalamus 9. Midbrain limbic nuclei

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

50. Amygdaloid complex

51. Within uncus Within uncus n Process sensory information n Determines emotional level, especially negative n Modulates affective expression Autonomic, endocrine and affective reactions Autonomic, endocrine and affective reactions –Aggression when stimulated –Calm, fearless in damage

52. Amygdaloid complex А. Corticomedial part B. Basolateral part C. Connections - Stria terminalis - Ventral amygdalofugal pathway

53. Connections of the Amygdala

54. Amygdaloid Nuclear Complex Emotion & Amygdala

55. AutismAutism Dysfunction of amygdala MercuryRising

58. Limbic subcortical nuclei (cont.) Conections Corpus amygdaloideum (stria terminalis) Habenula (stria medullaris) Corpus amygdaloideum, hippocampus (diagonal band of Брока) Orbitofrontal cortex, hypothalamus, midbrain (medial forebrain bundle) Area septalis Area septalis Septum precommissurale Septum precommissurale Nucleus tractus diagonalis (Broca) Septum pellucidum Septum pellucidum Nuclei septi pellucidi

59. - above substantia perforata anterior - Large cholinergic neurons - Afferents fron olfactory and limbic structures - Duffuse cortical projections - Damaged in cortical dementia (Alzhaeimer disease) (Alzhaeimer disease) Nucleus basalis of Meynart

60. - ventral striatum - Connection between limbic and extrapyramid system - Regulates processes of reward, motivation and addiction. Cocain and nicotine cause release of dopamin from its cotical part. Nucleus accumbens. Center of pleasure

61. PathwaysPathways 1. Fornix 2. Stria terminalis 3. Ventral amygdalofugal pathway 4. Stria medullaris thalami 5. Diagonal band of Broca 6. Fasciculus retroflexus

62. Limbic circuit of Papez