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(1)

2011.10.14.. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 1 Development of Complex Curricula for Molecular Bionics and Infobionics Programs within a consortial* framework**

Consortium leader

PETER PAZMANY CATHOLIC UNIVERSITY

Consortium members

SEMMELWEIS UNIVERSITY, DIALOG CAMPUS PUBLISHER

The Project has been realised with the support of the European Union and has been co-financed by the European Social Fund ***

**Molekuláris bionika és Infobionika Szakok tananyagának komplex fejlesztése konzorciumi keretben

***A projekt az Európai Unió támogatásával, az Európai Szociális Alap társfinanszírozásával valósul meg.

(2)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 2

BEVEZETÉS A FUNKCIONÁLIS NEUROBIOLÓGIÁBA

INTRODUCTION TO

FUNCTIONAL NEUROBIOLOGY

By Imre Kalló

Contributed by: Tamás Freund, Zsolt Liposits, Zoltán Nusser, László Acsády, Szabolcs Káli, József Haller, Zsófia Maglóczky, Nórbert Hájos, Emilia Madarász, György Karmos, Miklós Palkovits, Anita Kamondi, Lóránd Erőss, Róbert

Gábriel, Zoltán Kisvárdai, Zoltán Vidnyánszky

(3)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 3

Cerebellum:

its structure and neuronal network

Imre Kalló & Miklós Palkovits

Pázmány Péter Catholic University, Faculty of Information Technology

I. Macroscopic and microscopic structure

II. Functonal characterization of afferent and efferent connections

III. Cerebellar neuronal network.

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2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 4

Role of the cerebellum in the central organisation of movement

It occupies a determinative site in the hierarchy of movement regulation

Its basic function:

- initiation, coordination, execution, learning of movement - ongoing control of posture

It is in close relationship with the sensory and motor systems it receives information from

- muscles and joints through the spinal cord - special neurons of the spinal cord

- motor areas of the cerebral cortex

- neurons of the brainstem (oliva inferior, formatio reticularis) - vestibular system

- visual- and auditory system - associative cortical areas it provides information to

- the ascending and descending motor systems

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2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 5

Primary motor cortex

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2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 6

Descending lateral corticospinal pathway

Ref: Principles of Neural Science, 4th ed. Edited by Eric R. Kandel, James H. Schwartz, and Thomas M. Jessell. New York, McGraw-Hill Professional Publishing, 2000

(7)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 7

Site of motor planning and generation of motor programs

A Motor planning B Motor programs

Ref: Principles of Neural Science, 4th ed. Edited by Eric R. Kandel, James H. Schwartz, and Thomas M. Jessell. New York, McGraw-Hill Professional Publishing, 2000

(8)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 8

Subdivisions of thalamus with motor functions

thalamus

sma = supplementer motor area pma = premotor area

VA-VL = Ventral anterior and lateral nuclei VP = Ventral posterior complex

VPLo = Ventral posterolateral nucleus, pars oralis

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2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 9

Basic neuronal connections

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2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 10

Regulatory circuits

VLo = Ventral lateral nucleus, pars oralis VLc = Ventral lateral nucleus, pars caudalis

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2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 11

Location and gross anatomy of the cerebellum (rat)

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2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 12 Brainstem

Spinal cord

The cerebro-cerebellar circuit

Ref: Principles of Neural Science, 4th ed. Edited by Eric R. Kandel, James H. Schwartz, and Thomas M. Jessell. New York, McGraw-Hill Professional Publishing, 2000

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2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 13

Location and gross

anatomy of the

cerebellum (human)

(14)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 14

Phylogenetic subdivisions of the cerebellum

ARCHICEREBELLUM - posture

PALEOCEREBELLUM - muscle tone NEOCEREBELLUM - regulated

movement

(15)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 15

Functional anatomical subdivisions of the cerebellum

VESTIBULOCEREBELLUM = archicerebellum FLOCCULO-NODULAR LOBE

(balance, eyemovement) SPINOCEREBELLUM = paleocerebellum MEDIAL (VERMIS) + INTERMEDIATE CORTEX

(execution of movement) CEREBROCEREBELLUM = neocerebellum LATERAL CORTEX

(planning and control of movement)

(16)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 16

Structure of the cerebellum

Macroscopic structure

- vermis, hemispheres, lobes, folia

- peduncles - nuclei

(17)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 17

Microscopic anatomy of the

cerebellum:

structure of the vermis and the cerebellar lobes

are similar

vermis

(18)

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Cerebellar lobes, peduncles and deep nuclei

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Microscopic anatomy of

the

cerebellum:

middle cerebellar

peduncle

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Deep cerebellar nuclei

(21)

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Microscopic anatomy of

the

cerebellum:

Deep cerebellar

nuclei

(22)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 22

Cerebellar nuclei

FASTIGIUS (MEDIALIS)

EMBOLIFORMIS (ANTERIOR INTERPOSITUS)

GLOBOSUS (POSTERIOR INTERPOSITUS)

LATERALIS (DENTATUS)

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Functional anatomical subdivisions of cerebellum

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2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 24

Structure of the cerebellum MACROSCOPIC STRUCTURE

- vermis, hemispheres, lobes, folia - pedunculi

- nuclei

MICROSCOPIC STRUCTURE - cerebellar cortex

- layers

- cell types

(25)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 25

Layers of the cerebellar cortex:

1-3

Medulla: 4

f

e d

c

(26)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 26

Cell types of the cerebellar

cortex:

Note the size, and the number of cells in the

different

layers

(27)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 27

CELL TYPES

Cerebellar cortex

Purkinje cell -

granule cell +

basket cell -

Golgi cell -

stellate cell -

glial cells White matter

glial cells Cerebellar nuclei

neuron +

glial cells

(28)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 28

Characteristics of the cerebellar neurons

Cell types Layers Function Innervated neurons

Projection neuron

Purkinje cells Purkinje inhibitory Deep cerebellar and

vestibular nuclei Interneurons

Granule cells Granule cell excitatory Purkinje-, stellate- basket and Golgi cells

Basket cells Molecular inhibitory Purkinje cells

Stellate cells Molecular inhibitory Purkinje cells

Golgi cells Granule cell inhibitory Granule cells

(29)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 29

M

G

Cell types of the cerebellar

cortex:

location of different cell

types

P

(30)

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Two types of cerebellar afferents: mossy fibers

and climbing fibers

Cerebellar

glomerulus

(31)

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Purkinje cells

(32)

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Neuronal connections of the Purkinje cells

afferents efferents

(33)

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Neuronal connections of

the Purkinje cells

(34)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 34

Characteristics of the cerebellar neurons

Cell types Layers Function Innervated neurons

Projection neuron

Purkinje cells Purkinje inhibitory Deep cerebellar and

vestibular nuclei Interneurons

Granule cells Granule cell excitatory Purkinje-, stellate- basket and Golgi cells

Basket cells Molecular inhibitory Purkinje cells

Stellate cells Molecular inhibitory Purkinje cells

Golgi cells Granule cell inhibitory Granule cells

(35)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 35

Neuronal connections of

the granule cells

(36)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 36

Structure of the cerebellar

glomerulus

(37)

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Neuronal connections of

the granule cells

(38)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 38

Activation of Purkinje cells by the axons of granule cells (paralell

fibers)

Red: Dendritic trees of Purkinje cells innervated by granule cells

Green and Blue: Dendritic trees of

Purkinje cells innervated by inferior olive neurons located in different subdivisions of the nucleus

(39)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 39

Characteristics of the cerebellar neurons

Cell types Layers Function Innervated neurons

Projection neuron

Purkinje cells Purkinje inhibitory Deep cerebellar and

vestibular nuclei Interneurons

Granule cells Granule cell excitatory Purkinje-, stellate- basket and Golgi cells

Basket cells Molecular inhibitory Purkinje cells

Stellate cells Molecular inhibitory Purkinje cells

Golgi cells Granule cell inhibitory Granule cells

(40)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 40

Distribution of basket cells in the cerebellar cortex

Basket cells are marked by cJUN-immunoreactivity

(41)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 41

The cell body of basket cells are in the Purkinje cell layer M

G

(42)

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Lateral inhibition by

basket cells

(43)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 43

Characteristics of the cerebellar neurons

Cell types Layers Function Innervated neurons

Projection neuron

Purkinje cells Purkinje inhibitory Deep cerebellar and

vestibular nuclei Interneurons

Granule cells Granule cell excitatory Purkinje-, stellate- basket and Golgi cells

Basket cells Molecular inhibitory Purkinje cells

Stellate cells Molecular inhibitory Purkinje cells

Golgi cells Granule cell inhibitory Granule cells

(44)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 44

Localization and connectivity of stellate cells in the

cerebellar cortex

(45)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 45

Characteristics of the cerebellar neurons

Cell types Layers Function Innervated neurons

Projection neuron

Purkinje cells Purkinje inhibitory Deep cerebellar and

vestibular nuclei Interneurons

Granule cells Granule cell excitatory Purkinje-, stellate- basket and Golgi cells

Basket cells Molecular inhibitory Purkinje cells

Stellate cells Molecular inhibitory Purkinje cells

Golgi cells Granule cell inhibitory Granule cells

(46)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 46

Localization and connectivity of Golgi cells in the cerebellar

cortex

(47)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 47

Pathways of the cerebellum: the afferent connections

Pathways:

cerebrum (cortico-ponto-cerebellar) mossy fibers

spinal cord (spino-cerebellar) mossy fibers

oliva inferior (olivo-cerebellar) climbing fibers formatio reticularis (reticulo-cerebellar) mossy fibers vestibular system (vestibulo-cerebellar) mossy fibers

(48)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 48

The cerebro-ponto-cerebellar

pathway

(49)

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The cerebrocerebellum

(50)

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Information processing in the cerebro-cerebellar

pathway

(51)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 51

Pathways of the cerebellum: the afferent connections

Pathways:

cerebrum (cortico-ponto-cerebellar) mossy fibers

spinal cord (spino-cerebellar) mossy fibers

oliva inferior (olivo-cerebellar) climbing fibers formatio reticularis (reticulo-cerebellar) mossy fibers vestibular system (vestibulo-cerebellar) mossy fibers

(52)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 52

Structure, location and function of

the spinocerebellar pathway

(53)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 53

Spinocerebellum

(54)

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Origin of

spinocerebellar tracts

(55)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 55

Pathways of the cerebellum: the afferent connections

Pathways:

cerebrum (cortico-ponto-cerebellar) mossy fibers

spinal cord (spino-cerebellar) mossy fibers

oliva inferior (olivo-cerebellar) climbing fibers

formatio reticularis (reticulo-cerebellar) mossy fibers vestibular system (vestibulo-cerebellar) mossy fibers

(56)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 56

The olivo-

cerebellar tract

(57)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 57

Pathways of the cerebellum: the afferent connections

Pathways:

cerebrum (cortico-ponto-cerebellar) mossy fibers

spinal cord (spino-cerebellar) mossy fibers

oliva inferior (olivo-cerebellar) climbing fibers formatio reticularis (reticulo-cerebellar) mossy fibers vestibular system (vestibulo-cerebellar) mossy fibers

(58)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 58

The reticulo-cerebellar tract

(59)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 59

Pathways of the cerebellum: the afferent connections

Pathways:

cerebrum (cortico-ponto-cerebellar) mossy fibers

spinal cord (spino-cerebellar) mossy fibers

oliva inferior (olivo-cerebellar) climbing fibers formatio reticularis (reticulo-cerebellar) mossy fibers vestibular system (vestibulo-cerebellar) mossy fibers

(60)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 60

The vestibulocerebellum

(61)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 61

z z z

z z vestibular afferents

Termination fields of the afferent pathways in the

cerebellum

cortico-pontin afferents

spinal cord and brainstem afferents

(62)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 62

Pathways of the cerebellum: the efferent connections

Cerebello-cerebral pathway:

Purkinje cell → cerebellar nuclei →

→ thalamo-cortical

→ rubro-spinal

Cerebello-vestibular pathway:

→ Purkinje cell → vestibular nuclei → vestibulo-spinal

(63)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 63

Ventral motor nuclei of the thalamus

Execution of motor impulses

Integration of informations deriving from the cerebellum

and basal ganglia

Modulation of motor impulses

Co-ordination of motor impulses

(64)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 64

Dentato-thalamic and dentato-rubral

pathways

(65)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 65

Pathways of the cerebellum: the efferent connections

Cerebello-cerebral pathway:

Purkinje cell → cerebellar nuclei →

→ thalamo-cortical

→ rubro-spinal

Cerebello-vestibular pathway:

→ Purkinje cell → vestibular nuclei → vestibulo-spinal

(66)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 66

Pathways of the cerebellum: the efferent connections

Cerebello-cerebral pathway:

Purkinje cell → cerebellar nuclei →

→ thalamo-cortical

→ rubro-spinal

Cerebello-vestibular pathway:

→ Purkinje cell → vestibular nuclei → vestibulo-spinal

(67)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 67

Structure, location and function of the cerebello-

vestibular pathway

(68)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 68 regions informations nucleus

vermis vestibular fastigial medial system: coordination of

labyrinth, vestibularis nucleus, movements

spinal cord reticular formation,

(upper part motor cortex

Spinocerebellum of the body)

cranial nerves (head, neck)

intermediate spinal cord interpositus lateral system: coordination of

cortex (lower part nucleus ruber (magno- movements

of the body) cellular), distal motor cortex

Cerebrocerebellum lateral cortex cerebral dentate integrative system: initiation of

cortex nucleus ruber (parvo- movements,

cellular), planning and

premotor cortex temporal-tuning

(area 6) of movements

Vestibulocerebellum flocculonodular vestibular lateral medial system: posture,

lobe labyrinth vestibular motoneurons vestibular

reflexes

(69)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 69

Cerebellar network model

Activation of Purkinje cells - climbing fibers

- stimulation of single Purkinje cells - Golgi cell, inhibition by basket cells

- mossy fibers - glomerulus – activation by T-axons

(70)

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Cerebellar network model

(71)

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Cerebellar network model

(72)

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Cerebellar network model

(73)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 73

Cerebellar network model

Activation of Purkinje cells (signal divergence) - climbing fibers

- stimulation of single Purkinje cells - Golgi cell, inhibition by basket cells

-mossy fibers - glomerulus – activation by T-axons

- Output – signal originating from Purkinje cells (signal convergence) - cerebellar nuclei → efferent pathways

(74)

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Cerebellar network model

(75)

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Cerebellar network model

(76)

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Cerebellar network model

Basal ganglia

Premotor cortical areas Sensory

associative cortex

Cerebro-

cerebellum Cerebellum Motor cortex Motoneurons

Receptors Sensory cortical areas

Peripheral receptors

Planning and programing

Execution Movement

Feedback signals Sensory signals

Cerebellar network model

(77)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 77

Cerebellar network model

Planning and programing

Execution Movement

Feedback signals Sensory signals

Peripheral receptors

Sensory cortical areas Receptors

Motoneurons Premotor

cortical areas

Cerebro- cerebellum Sensory association

cortex

Basal ganglia

Spino- cerebellum

Motor cortex Cere-

bellum

(78)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 78

Cerebellar network model

Planning and programing

Execution Movement

Feedback signals Sensory signals

Peripheral receptors

Sensory cortical areas Receptors

Motoneurons Premotor

cortical areas

Cerebro- cerebellum Sensory association

cortex

Basal ganglia

Spino- cerebellum

Motor cortex Cere-

bellum

(79)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 79

Cerebellar network model

Planning and programing

Execution Movement

Feedback signals Sensory signals

Peripheral receptors

Sensory cortical areas Receptors

Motoneurons Premotor

cortical areas

Cerebro- cerebellum Sensory association

cortex

Basal ganglia

Spino- cerebellum

Motor cortex Cere-

bellum

(80)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 80

Cerebellar network model

Planning and programing

Execution Movement

Feedback signals Sensory signals

Peripheral receptors

Sensory cortical areas Receptors

Motoneurons Premotor

cortical areas

Cerebro- cerebellum Sensory association

cortex

Basal ganglia

Spino- cerebellum

Motor cortex Cere-

bellum

(81)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 81

Cerebellar network model

Planning and programing

Execution Movement

Feedback signals Sensory signals

Peripheral receptors

Sensory cortical areas Receptors

Motoneurons Premotor

cortical areas

Cerebro- cerebellum Sensory association

cortex

Basal ganglia

Spino- cerebellum

Motor cortex Cere-

bellum

(82)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 82

Cerebellar network model

Planning and programing

Execution Movement

Feedback signals Sensory signals

Peripheral receptors

Sensory cortical areas Receptors

Motoneurons Premotor

cortical areas

Cerebro- cerebellum Sensory association

cortex

Basal ganglia

Spino- cerebellum

Motor cortex Cere-

bellum

(83)

2011.10.14. TÁMOP – 4.1.2-08/2/A/KMR-2009-0006 83

Cerebellar network model

Planning and programing

Execution Movement

Feedback signals Sensory signals

Peripheral receptors

Sensory cortical areas Receptors

Motoneurons Premotor

cortical areas

Cerebro- cerebellum Sensory association

cortex

Basal ganglia

Spino- cerebellum

Motor cortex Cere-

bellum

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