Smells are surer than Smells are surer than

sounds and sights to sounds and sights to

make your heart-strings make your heart-strings

crack.crack.

- - Rudyard KiplingRudyard Kipling

Olfactory systemOlfactory system

ConveysConveys specific visceral sensationspecific visceral sensation ( (smellsmell) ) viavia n. olfactorius.n. olfactorius.

Does not relay Does not relay in the thalamusin the thalamus.. Connections withConnections with thalamusthalamus, , hypothalamus, hypothalamus,

amygdaloid complexamygdaloid complex && hippocampal formationhippocampal formation..

Structure of the olfactory systemStructure of the olfactory system

І. І. Receptor cellsReceptor cells

ChemoreceptorsChemoreceptors.. AboutAboutоо 25 25 billionsbillions on each sideon each side.. Located in theLocated in the nasal mucosanasal mucosa. . RegenerateRegenerate.. 11stst order neurons order neurons in the olfactory pathwayin the olfactory pathway.. Bipolar neuronsBipolar neurons,, unmyelynated axons formunmyelynated axons form nn. nn.

оlfactоriiоlfactоrii.. InIn bulbus olfactorius the axons synapse withbulbus olfactorius the axons synapse with the the

mitral cellsmitral cells in olfactory glomerulusin olfactory glomerulus..

Nervi olfactoriiNervi olfactorii

II. Bulbus olfactoriusII. Bulbus olfactorius

OnOn lamina cribrosalamina cribrosa ofof os ethmoidaleos ethmoidale Entered by olfactory nervesEntered by olfactory nerves.. 6-layered 6-layered structurestructure.. 4 4 cell typescell types::

– periglomerularperiglomerular - - inhibitoryinhibitory– tuftedtufted - - efferentefferent (ІІ (ІІ orderorder))– mitralmitral - - efferentefferent (ІІ (ІІ orderorder)) – granulegranule - - inhibitoryinhibitory

GlomerulusGlomerulus – – polysynaptic structurepolysynaptic structure, , ensuringensuring conversionconversion of olfactory impulsesof olfactory impulses on the mitral cells.on the mitral cells.

Bulbus olfactoriusBulbus olfactorius

Bulbus olfactorius -Bulbus olfactorius -клетъчен клетъчен съставсъстав

Synaptic organization ofSynaptic organization of bulbus olfactoriusbulbus olfactorius

Dendrodendrite synapses

Glutamate (excitory)GABA (inhibitory)

Types of synapsesTypes of synapses

Lateral inhibition.

ІІІІІІ. . Tractus olfactorius:Tractus olfactorius:– inin sulcus olfactoriussulcus olfactorius..– Axons of mitral and tufted cellsAxons of mitral and tufted cells..– nucl. olfactorius anterior nucl. olfactorius anterior ((modulatormodulator))::– terminates interminates in trigonum olfactorium.trigonum olfactorium.

ІVІV. . Stria olfactoria lateralisStria olfactoria lateralis– to primary olfactory cortex throughto primary olfactory cortex through limen insulaelimen insulae

VV. . Stria olfactoria medialisStria olfactoria medialis– toto area subcalosa andarea subcalosa and gyrus paraterminalisgyrus paraterminalis

Tractus olfactorius

VІVІ. . Olfactory corexOlfactory corex PrimaryPrimary

– onon uncusuncus ((area area 3434 afterafter BrodmannBrodmann))..

– fibers fromfibers from stria olfactoria lateralis.stria olfactoria lateralis.

– containscontains prepiriformprepiriform && periamygdaloid areasperiamygdaloid areas..

– connectins withconnectins with nucl. medialis dorsalis of thalamus, nucl. medialis dorsalis of thalamus, hypothalamus, hipocampal formationhypothalamus, hipocampal formation..

SecondarySecondary– entorhinal areaentorhinal area ofof gyrus parahippocampalis gyrus parahippocampalis ((areaarea 28 28).).

– Impulses from primary areasImpulses from primary areas..

– efferents to hippocampus.efferents to hippocampus. Orbitofrontal cortexOrbitofrontal cortex

– Impulses fromImpulses from nucl. medialis dorsalis thalaminucl. medialis dorsalis thalami– conscious preception of smell.conscious preception of smell.

Olfactory corexOlfactory corex

Orbitofrontal cortexOrbitofrontal cortex

We need our orbitofrontal cortex to make intelligent We need our orbitofrontal cortex to make intelligent choices. Its individual cells code for value.choices. Its individual cells code for value.

Ann Thomson, Nature NeuroscienceAnn Thomson, Nature Neuroscience

Pathways in the olfactory systemPathways in the olfactory system

Limbic system

Limbic systemLimbic systemLimbic systemLimbic system

Morphological substrate Morphological substrate of emotionsof emotions and behaviourand behaviour..

Role inRole in emotional behavioremotional behavior, , feedingfeeding, , defensive defensive

reactionreaction, , sexual behavioursexual behaviour, , memorymemory and learningand learning..

Functions Functions mediatedmediated through through hypothalamus andhypothalamus and

autonomic systemautonomic system..

ContainsContains corticalcortical && subcorticalsubcortical ( (nucleinuclei) ) structuresstructures..

AffectiveAffectivebehaviorbehavior

EmotionEmotion

HappinessHappinessandandGriefGrief

IntroductionIntroductionIntroductionIntroduction

ConceptConceptBroca (1877) - ‘La Grand Lobe Limbique’Broca (1877) - ‘La Grand Lobe Limbique’

Papez (1937) - ‘Limbic Circuit’ - Papez (1937) - ‘Limbic Circuit’ - emotionemotionMacLean (1952) - ‘Limbic System’ – MacLean (1952) - ‘Limbic System’ – visceral brainvisceral brain

Nauta (1972) - ‘Septo-hypothalamo-mesencephalic continuum’Nauta (1972) - ‘Septo-hypothalamo-mesencephalic continuum’

JAMES PAPEZ (1883-1958)

PAUL BROCA (1824-1880)

Paul D. MacLean (1913- )Paul D. MacLean (1913- )

Limbic systemLimbic system- - Term ofTerm of Paul MacLeanPaul MacLean (1952) (1952)

- - Visceral brainVisceral brain-Triple conceptTriple concept

of brain evolutionof brain evolution

HypothalamusHypothalamus

Nucleus accumbensNucleus accumbens

Nucleus amygdaloideusNucleus amygdaloideus

Cortex orbitofrontalisCortex orbitofrontalis

Some psychiatric implications onSome psychiatric implications onphysiological studies on fronto-physiological studies on fronto-temporal portions of limbic systemtemporal portions of limbic system(visceral brain). Electroencephalogr(visceral brain). ElectroencephalogrClin Neurophysiol 4: 407-418, 1952Clin Neurophysiol 4: 407-418, 1952

Septo-(Preoptico)-Hypothalamo- Mesencephalic ContinuumSepto-(Preoptico)-Hypothalamo- Mesencephalic ContinuumSepto-(Preoptico)-Hypothalamo- Mesencephalic ContinuumSepto-(Preoptico)-Hypothalamo- Mesencephalic Continuum

Parts of the limbic systemParts of the limbic systemParts of the limbic systemParts of the limbic system

AreaAreaseptalisseptalis

AreaAreaseptalisseptalis HypothalamusHypothalamus HypothalamusHypothalamus

MidbrainMidbrain MidbrainMidbrain HippocampalHippocampalformationformation

HippocampalHippocampalformationformation

Olfactory Olfactory cortexcortex

Olfactory Olfactory cortexcortex

AmygdaloidAmygdaloidcomplexcomplex

AmygdaloidAmygdaloidcomplexcomplex

SpinalSpinalcordcord

&&BrainBrainstemstem

SpinalSpinalcordcord

&&BrainBrainstemstem

Limbic system

Expression ofExpression ofemotionemotion

Septo-Septo-

hypothalamo-hypothalamo-

mesencephalicmesencephalic

continuumcontinuum

Parts of the limbic systemParts of the limbic systemParts of the limbic systemParts of the limbic system

TELENCEPHALONTELENCEPHALON Lobus LimbicusLobus Limbicus Gyrus FornicatusGyrus Fornicatus Gyrus CingulatusGyrus Cingulatus Gyrus ParahippocampalisGyrus Parahippocampalis Hippocampal FormationHippocampal Formation HippocampusHippocampus Gyrus DentatusGyrus Dentatus SubiculumSubiculum Hippocampal RudimentsHippocampal Rudiments Gyrus FasciolarisGyrus Fasciolaris Indusium GriseumIndusium Griseum

Cortex Olfactorius (Rhinencephalon)Cortex Olfactorius (Rhinencephalon)

- Lobus Piriformis- Lobus Piriformis

Cortex PrepiriformisCortex Prepiriformis

Cortex PeriamygdaloideusCortex Periamygdaloideus

Cortex EntorhinalisCortex Entorhinalis

Basal forebrainBasal forebrain Substantia InnominataSubstantia Innominata Nucleus Basalis Nucleus Basalis нана Meynert Meynert Pallidum VentralisPallidum Ventralis Nucleus Accumbens (Septi)Nucleus Accumbens (Septi)Regio SeptalisRegio Septalis Area SeptalisArea Septalis GyrusGyrus ParaterminalisParaterminalis Gyrus SubcallosusGyrus Subcallosus Nuclei SeptalisNuclei Septalis DorsalDorsal, , laterallateral andand medialmedial Nuclei SeptalisNuclei Septalis Nucleus Stria Diagonalis BrocaNucleus Stria Diagonalis Broca Nucleus Stria TerminalisNucleus Stria TerminalisCorpus Amygdaloideum Corpus Amygdaloideum Pars CorticomedialisPars Corticomedialis Pars BasolateralisPars Basolateralis Nucleus CentralisNucleus Centralis

LobLobusus Limbic LimbicususLobLobusus Limbic Limbicusus

Lobus LimbicusLobus Limbicus Gyrus FornicatusGyrus Fornicatus

GyrusGyrus CinguliCinguli Gyrus ParahippocampalisGyrus Parahippocampalis AreaArea EntorhinalisEntorhinalis IsthmusIsthmus Hippocampal FormationHippocampal Formation Hippocampus ProperHippocampus Proper (Ammon’s horn)(Ammon’s horn) Gyrus DentatusGyrus Dentatus SubiculumSubiculum Hippocampal RudimentsHippocampal Rudiments GyrusGyrus FasciolarisFasciolaris Indusium GriseumIndusium Griseum

Класификация на коратаКласификация на кората

Isocortex Isocortex - Neocortex- Neocortex

AllocortexAllocortex

ArchicortexArchicortex

HippocampusHippocampus

Gyrus DentatusGyrus Dentatus

PaleocortexPaleocortex

BulbusBulbus OlfactoriusOlfactorius

Lobus PiriformisLobus Piriformis

Mesocortex (Juxtallocortex,Mesocortex (Juxtallocortex,

Periallocortex, Mesallocortex)Periallocortex, Mesallocortex)

GyrusGyrus CinguliCinguli

Parts of the limbic systemParts of the limbic systemParts of the limbic systemParts of the limbic system

Limbic cortexLimbic cortexLimbic cortexLimbic cortex

OnOn medial aspectmedial aspect of the hemispheresof the hemispheres

ArchicortexArchicortex

– In some partsIn some parts paleo- &paleo- & neocortex.neocortex.

External ringExternal ring

Internal ringInternal ring

Limbic cortexLimbic cortexLimbic cortexLimbic cortex

External ringExternal ring-- gyrus cinguli gyrus cinguli

-- area subcallosa area subcallosa

-- gyrus parahippocampalis gyrus parahippocampalis

-- uncus.uncus.

Internal ringInternal ring

-- gyrus paraterminalisgyrus paraterminalis

-- indusium griseumindusium griseum

- - Hippocampal formationHippocampal formation..

Hippocampus Proper Hippocampus Proper

(Ammon’s horn, (Ammon’s horn,

Cornu Ammonis)Cornu Ammonis)

Gyrus DentatusGyrus Dentatus

SubiculumSubiculum

Hippocampal formationHippocampal formation

Hippocampal formationHippocampal formationHippocampal formationHippocampal formation Hippocampus Hippocampus –– cortical fold in the lateral cortical fold in the lateral

ventricleventricle caused bycaused by sulcus hippocampisulcus hippocampi

- 3-layered- 3-layered aarchicortexrchicortex-- sstratum pyramidale tratum pyramidale - - efferentsefferents, , formingforming

alveusalveus and and fimbria hippocampifimbria hippocampi

-- sstratum molecularetratum moleculare- stratum radiatumstratum radiatum

- Subiculum (paleocortex)Subiculum (paleocortex)-- affrents from affrents from h hippocampusippocampus

-- efferents to efferents to co corpora mamillaria andrpora mamillaria and nucl. anterior thalaminucl. anterior thalami

Parasubiculum (paleocortex)Parasubiculum (paleocortex)-- transition to transition to gyr. parahippocampalisgyr. parahippocampalis

1. uncus1. uncus

2. gyrus dentat2. gyrus dentatusus

3. fornix3. fornix

4. corpus callosum4. corpus callosum

5. gyrus fasciolaris5. gyrus fasciolaris

6. sulcus 6. sulcus

hippocampalishippocampalis

7. gyrus 7. gyrus

parahippocampal parahippocampal

8. sulcus collateralis8. sulcus collateralis

Hippocampal formationHippocampal formation

Hippocampal formationHippocampal formation ((lateral viewlateral view))

Hippocampal formationHippocampal formation (medial view)(medial view)

Archicortex - 3 Archicortex - 3 layerslayers

Hippocampus ProperHippocampus Proper Str. MoleculareStr. Moleculare

Str. PyramidaleStr. Pyramidale

Str. PolymorpheStr. Polymorphe

Gyrus DentatusGyrus Dentatus Str. MoleculareStr. Moleculare

Str. Str. GranulareGranulare

Str. PolymorpheStr. Polymorphe

SubiculumSubiculum TransientTransient betweenbetween hippocampalhippocampal archicortex archicortex and entorhinaland entorhinal paleocortex paleocortex

Hippocampal formationHippocampal formation - - ArchicortexArchicortex

Classification of the cortexClassification of the cortex

IsocortexIsocortex 66-layered cortex-layered cortex

homotypicalhomotypical andand

heterotypicalheterotypical

Allocortex Allocortex

PaleocortexPaleocortex olfactory cortexolfactory cortex

- lobus piriformis- lobus piriformis

ArchicortexArchicortex 33-layered-layered

- - hippocampal formationhippocampal formation

Archicortex Archicortex - - afterafter Ramon y Cajal Ramon y Cajal

7. stratum 7. stratum molecularemoleculare

6. stratum 6. stratum lacunosumlacunosum

5. stratum 5. stratum radiatumradiatum

4. stratum4. stratum pyramidalispyramidalis

3. stratum oriens3. stratum oriens

2. alveus2. alveus

1. ependyma1. ependyma

Hippocampus and memoryHippocampus and memory

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

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

Connection in the hippocampal formationConnection in the hippocampal formation

1. 1. Internal connectionsInternal connectionstrisynaptic pathwaytrisynaptic pathway

2. 2. Afferent connectionsAfferent connections perforantperforant andand alveolar pathwayalveolar pathway

3. 3. Efferent connctionsEfferent connctions

fornixfornix

Internal connectionsInternal connections

Classical 3-neuron pathwayClassical 3-neuron pathway

1. 1. Енторинална кораЕнторинална кора ( (perforant pathwayperforant pathway)) granule cell ofgranule cell of gyrus dentatusgyrus dentatus

2. 2. Granules cellsGranules cells (mossy fiber) (mossy fiber) CA3 CA3 pyramid cellspyramid cells

3. 3. Pyramid cellsPyramid cells (Schaffer collateral) (Schaffer collateral)

CA1 CA1 pyramid cellspyramid cells

subiculum subiculum cortex entorhinalis cortex entorhinalis

AfferentsAfferents

FromFrom Cortex Entorhinalis Cortex Entorhinalis

Alveolar pathwayAlveolar pathway from medialfrom medial EC EC toto CA1 CA1 andand Subiculum Subiculum

Perforant pathwayPerforant pathway from medialfrom medial EC EC toto CA1, CA2, CA3 CA1, CA2, CA3 &&

Gyrus DentatusGyrus Dentatus

EfferentsEfferents

FORNIXFORNIX

AlveusAlveus

FimbriaeFimbriae

CrusCrus

CommissurCommissurаа

Corpus Corpus

ColumnColumn

EfferentsEfferents

FornixFornix -- from pyramid cells offrom pyramid cells of hippocampus & subiculum hippocampus & subiculum

- 1.2 million - 1.2 million fibersfibers

PostcommissiralPostcommissiral Fornix Fornix – – basic bundlebasic bundle

toto Corpus MammillareCorpus Mammillare

Thalamus AnteriorThalamus Anterior

Nuclei Septi LateralisNuclei Septi Lateralis

Hypothalamus Hypothalamus

Tegmentum Tegmentum of midbrainof midbrain

EfferentsEfferents

PrecommissuralPrecommissural Fornix Fornix – – smallersmaller

- - mainly frommainly from hippocampus proper hippocampus proper

toto Nuclei Septi Nuclei Septi

Area Preoptica LateralisArea Preoptica Lateralis

Area Hypothalamica AnteriorArea Hypothalamica Anterior

Nucleus Striae Diagonalis BrocaNucleus Striae Diagonalis Broca

Nucleus AccumbensNucleus Accumbens

Medial aspect of frontal lobeMedial aspect of frontal lobe

Nucleus Caudatus &Nucleus Caudatus & PutamenPutamen

Amygdala & ClaustrumAmygdala & Claustrum

EfferentEfferent FORNIXFORNIX from pyramid cellsfrom pyramid cells hippocampus & subiculumhippocampus & subiculum Alveus, Fimbriae, CrusAlveus, Fimbriae, Crus Commissure, Corpus, ColumnCommissure, Corpus, Column PrecommissuralPrecommissural Fornix Fornix toto Nuclei Septal, Nuclei Septal, Nucleus AccumbensNucleus Accumbens Area Hypothalamica AnteriorArea Hypothalamica Anterior Nucleus Olfactorius AnteriorNucleus Olfactorius Anterior PostcommissuralPostcommissural Fornix Fornix toto Corpus Mammillare Corpus Mammillare Thalamus AnteriorThalamus Anterior HypothalamusHypothalamus Nucleus StriaNucleus Striaее Terminalis Terminalis

AfferentAfferent Entorhinal CortexEntorhinal Cortex Alveolar pathwayAlveolar pathway medialmedial EC EC toto CA1 CA1 andand Subiculum Subiculum Perforant pathwayPerforant pathway from lateralfrom lateral EC EC toto CA1, CA2, CA3 CA1, CA2, CA3 andand GyrusDentatus GyrusDentatus

GyrusGyrus DentatuseDentatuse Mossy fiber Mossy fiber - CA3- CA3 - - Schaefer fiber Schaefer fiber (CA3-CA1)(CA3-CA1)

OthersOthers Hypothalamus, Nuclei Septi, Hypothalamus, Nuclei Septi, Substantia InnominataSubstantia Innominata MidbrainMidbrain

Summary of connectionsSummary of connections

Subcortical limbic structuresSubcortical limbic structuresSubcortical limbic structuresSubcortical limbic structures

11. . Amygdaloid complexAmygdaloid complex

2. 2. Mammillary bodyMammillary body

3. 3. Septal areaSeptal area

4. 4. Nucleus anterior, Nucleus anterior, nnucleus medialis dorsalis & ucleus medialis dorsalis & nuclei intralaminares thalami nuclei intralaminares thalami

5. Nucleus accumbems5. Nucleus accumbems

6. Substantia innominata6. Substantia innominata

7. Nuclei habenulae7. Nuclei habenulae

8. 8. HypothalamusHypothalamus

9. 9. Midbrain limbic nucleiMidbrain limbic nuclei

Amygdala

L. almond

K. F. Burdach’s

term

Amygdaloid complexAmygdaloid complex

Amygdaloid complexAmygdaloid complexAmygdaloid complexAmygdaloid complex

WithinWithin uncusuncus

Process sensory informationProcess sensory information

Determines emotional levelDetermines emotional level, , especially negativeespecially negative

Modulates affective expressionModulates affective expression

AutonomicAutonomic, , endocrineendocrine andand affective reactionsaffective reactions

– Aggression when stimulatedAggression when stimulated

– CalmCalm, , fearless in damagefearless in damage

Amygdaloid complexAmygdaloid complexAmygdaloid complexAmygdaloid complex

А. А. Corticomedial partCorticomedial part

BB. . Basolateral partBasolateral part

CC. . ConnectionsConnections

- Stria terminalis- Stria terminalis

- - Ventral amygdalofugal pathwayVentral amygdalofugal pathway

Connections of the AmygdalaConnections of the AmygdalaConnections of the AmygdalaConnections of the Amygdala

Amygdaloid Nuclear ComplexAmygdaloid Nuclear ComplexAmygdaloid Nuclear ComplexAmygdaloid Nuclear Complex

EmotionEmotion& & AmygdalaAmygdala

AutismAutismAutismAutism

Dysfunction ofDysfunction of

amygdalaamygdala

MercuryMercuryRisingRising

Limbic subcortical nucleiLimbic subcortical nuclei ((contcont.).)Limbic subcortical nucleiLimbic subcortical nuclei ((contcont.).)

ConectionsConectionsCorpus amygdaloideumCorpus amygdaloideum (stria terminalis) (stria terminalis)

Habenula (stria medullaris)Habenula (stria medullaris)

Corpus amygdaloideum, hippocampus (diagonal band ofCorpus amygdaloideum, hippocampus (diagonal band of Брока Брока))

Orbitofrontal cortexOrbitofrontal cortex, , hypothalamushypothalamus, , midbrain (medial forebrain bundle) midbrain (medial forebrain bundle)

Area septalisArea septalis Septum precommissuraleSeptum precommissurale

NNucleus tractus diagonalis ucleus tractus diagonalis (Broca)(Broca)

Septum pellucidumSeptum pellucidum

Nuclei septi pellucidiNuclei septi pellucidi

- aboveabove substantia perforata anterior substantia perforata anterior

- Large cholinergic neuronsLarge cholinergic neurons

- Afferents fron olfactory and limbic Afferents fron olfactory and limbic

structuresstructures

- Duffuse cortical projectionsDuffuse cortical projections- Damaged in cortical dementiaDamaged in cortical dementia ((Alzhaeimer diseaseAlzhaeimer disease))

Nucleus basalis ofNucleus basalis of MeynartMeynartNucleus basalis ofNucleus basalis of MeynartMeynart

- - ventralventral striatumstriatum-- Connection betweenConnection between limbiclimbic andand extrapyramid systemextrapyramid system- Regulates processes of reward, motivation and addiction. Cocain and nicotine cause release of dopamin from its cotical part.

Nucleus accumbens. Center of Nucleus accumbens. Center of pleasurepleasure

PathwaysPathwaysPathwaysPathways

11. . FornixFornix

2. Stria terminalis2. Stria terminalis

3. Ventral amygdalofugal pathway3. Ventral amygdalofugal pathway

4. 4. Stria medullaris thalamiStria medullaris thalami

5. 5. Diagonal band ofDiagonal band of BrocaBroca

6. Fasciculus retroflexus6. Fasciculus retroflexus

Limbic circuit ofLimbic circuit of PapezPapezLimbic circuit ofLimbic circuit of PapezPapez