Central Nervous System

1. Principles of neural organization 2. Spinal cord 3. Brainstem V medulla oblongata V pons V midbrain 4. Cerebellum 5. Forebrain V diencephalon, hypothalamus V Principles of neural organization ° nerve cells (neurons) – at least 10 billion V cell body (perikaryon, soma) V axon – myelinated or unmyelinated V dendrites ° glial cells (neuroglia): V astrocytes less than 1 mm to more than 1 m V oligodendrocytes, Schwann cells in length V microglia V ependymal cells

Prof. Dr. Nikolai Lazarov 2 Classification of the nervous system

Prof. Dr. Nikolai Lazarov 3 Adult brain structures ° encephalon (brain): V telencephalon (‘endbrain’) V diencephalon (‘between brain’) V mesencephalon (midbrain) V pons V cerebellum V medulla oblongata ° spinal cord ° functional parts: V cerebrum V brain stem V cerebellum

Prof. Dr. Nikolai Lazarov 4 Spinal cord Spinal cord – topographic location ° topography and levels – in the vertebral canal V fetal life – the entire length of vertebral canal V at birth – near the level L3 vertebra V adult – upper ⅔ of vertebral canal (L1-L2) ° average length: V ♂ – 45 cm long V ♀ – 42-43 cm ° diameter ~ 1-1.5 cm (out of enlargements) ° weight ~ 35 g (2% of the CNS) ° shape – round to oval (cylindrical) ° terminal part: V conus medullaris V filum terminale internum (cranial 15 cm) – S2 V filum terminale externum (final 5 cm) – Co2 V cauda equina – collection of lumbar and sacral spinal nerve roots

Prof. Dr. Nikolai Lazarov 5 Spinal cord Macroscopic anatomy – enlargements

° cervical enlargement, intumescentia cervicalis: V spinal segments (C4-Th1) V vertebral levels (C4-Th1) V provides upper limb innervation (brachial plexus) ° lumbosacral enlargement, intumescentia lumbosacralis: V spinal segments (L2-S3) V vertebral levels (Th9-Th12) V segmental innervation of lower limb (lumbosacral plexus)

Prof. Dr. Nikolai Lazarov 6 Spinal cord External surface structure

° Two symmetrical halves : V divided by two external longitudinal grooves: ‹ a deeper anterior median fissure ‹ a shallower posterior median sulcus (less prominent) V joined by a commissural band of nervous tissue

Prof. Dr. Nikolai Lazarov 7 Spinal cord Segmental structure ° 31 segments: V 8 cervical V 12 thoracic V 5 lumbar V 5 sacral V 1 coccygeal ° segment ≠ vertebra: V growth of the vertebral column exceeds that of the spinal cord V all segments terminate above level L1/L2 Ù cauda equina V vary in diameter and length

Prof. Dr. Nikolai Lazarov 8 Spinal cord Internal structure of the spinal cord ° grey matter, substantia grisea V butterfly-like or H-shaped ° white matter, substantia alba ° vary in diameter and length at different levels

Prof. Dr. Nikolai Lazarov 9 Spinal cord Grey matter, substantia grisea

° composition: V neuronal perikarya V dendrites with their synapses V glial supporting cells V blood vessels ° anterior (ventral) column: V cornu anterius (columna anterior) ° posterior (dorsal) column: V cornu posterius (columna posterior) ° lateral column: V cornu laterale – Th1-L2; S2-S4 (columna intermedia) ° central canal: V canalis centralis Ù liquor cerebrospinalis V substantia gelatinosa centralis ° grey commissure: V commissura grisea

Prof. Dr. Nikolai Lazarov 10 Spinal cord General structure of the grey matter

° posterior column (dorsal horn): V apex, caput, cervix, basis V projection neurons (neurocyti funiculares ) and interneurons (neurocyti interni) ° lateral column (intermediolateral horn ): V visceromotor neurons ‹ parasympathetic ‹ sympathetic ° anterior column (ventral horn): V motor neurons ( neurocyti radiculares ) ‹ large alpha motoneurons (ACh) ‹ small gamma motoneurons (ACh) ‹ Renshaw cells (Gly) (inhibitory interneurons)

Prof. Dr. Nikolai Lazarov 11 Spinal cord White matter composition

° composition: ■ 3 columns (funiculi) – ascending and descending tracts V nerve fibers V posterior funiculus: funiculus dorsalis (posterior) V glia V blood vessels

V lateral funiculus: funiculus lateralis

V anterior funiculus: funiculus ventralis (anterior)

Prof. Dr. Nikolai Lazarov 12 Spinal cord Reflex arcs of the spinal cord

° reflex arc – the neural pathway that mediates a reflex action ° two types of reflex arcs: V autonomic reflex arc (affecting inner organs) V somatic reflex arc (affecting muscles) ° monosynaptic vs. polysynaptic reflex arcs

‘Final common path( way )’ (of Sherrington) Prof. Dr. Nikolai Lazarov 13 Spinal cord Patellar Reflex Testing

Prof. Dr. Nikolai Lazarov 14 Spinal cord Meningeal coverings ° three meninges: V dura mater ‹epidural and subdural spaces V arachnoid mater ‹subarachnoid space Ù (liquor) V pia mater (leptomeninges) ‹perivascular spaces Ù spinal blood vessels

Prof. Dr. Nikolai Lazarov 15 Brain stem General organization of the brainstem ° 3 subdivisions: V medulla oblongata V pons V midbrain ° 10 cranial nerves attached (with the exception of nn . I and II) V motor and sensory innervation: face&neck ° pathway for: V all fiber tracts passing up and down ° 3 laminae: tectum, tegmentum, basis ° neurological functions: V survival ‹ breathing ‹ digestion ‹ heart rate ‹ blood pressure V arousal ‹ being awake and alert

Prof. Dr. Nikolai Lazarov 16 Medulla oblongata Medulla oblongata – external features

° synonyms: bulbus, myelencephalon ° shape – pyramidal or conical ° size: V 3 cm longitudinally V 2 cm transversally V 1.25 cm anteroposteriorly ° 2 parts: V lower, closed part V upper, open part ° functions: V relay station of motor tracts V contains respiratory, vasomotor and cardiac centers V controls reflex activities such as coughing, gagging, swallowing and vomiting

Prof. Dr. Nikolai Lazarov 17 Medulla oblongata Medulla oblongata – anterior aspect ° anterior median fissure ° pyramid Ù pyramidal decussation ° olive ° anterolateral sulcus Ù hypoglossal nerve (XII) ° retroolivar sulcus Ù nn. IX, X and XI

Prof. Dr. Nikolai Lazarov 18 Medulla oblongata Medulla oblongata – posterior aspect ° posterior median sulcus ° caudal, closed part – : V gracile fascicle Ù gracile tubercle V cuneate fascicle Ù cuneate tubercle V posterior intermediate sulcus V posterolateral sulcus V trigeminal tubercle V tuberculum cinereum

Prof. Dr. Nikolai Lazarov 19 Medulla oblongata Medulla oblongata – posterior aspect

° cranial, open part – : V medullary striae of ˜ obex V V hypoglossus triangle V vagus triangle V V vestibular area, acoustic tubercle Ù pons V inferior cerebellar peduncle Ù cerebellum

Prof. Dr. Nikolai Lazarov 20 Medulla oblongata Medulla oblongata – internal structure ° white and grey matter ° olive: V inferior olivary nuclear complex ° posterior column nuclei: V nucleus gracilis V nucleus cuneatus V internal arcuate fibers Ù sensory decussation Ù medial lemniscus Ù bulbothalamic tract V external arcuate fibers ‹ posterior Ù cuneocerebellar tract ‹ anterior Ù bulbocerebellar tract

° reticular nuclei: V raphe nuclei, pallidus, obscurus & magnus – SERergic (B1-B3) Prof. Dr. Nikolai Lazarov 21 Medulla oblongata Grey matter: nuclei of the cranial nerves

° glossopharyngeal nerve (IX): V inferior salivatory nucleus V nucleus ambiguus (IX, X, XI) V solitary tract nucleus (VII, IX, X) ° vagus nerve (X): V dorsal motor nucleus of the vagus ° accessorius nerve (XI) ° hypoglossal nerve (XII): V hypoglossal nucleus ° trigeminal nerve (V): V spinal trigeminal nucleus

Prof. Dr. Nikolai Lazarov 22 White matter: Medulla oblongata ascending and descending tracts ° descending (corticobulbar) tracts: V corticospinal tract Ù pyramidal decussation V reticulospinal tract ° ascending tracts: V cuneocerebellar tract V anterior and posterior spinocerebellar tracts V anterior and lateral spinothalamic tracts V spinotectal tract ° mixed tracts: V dorsal longitudinal fasciculus: ‹ descending hypothalamic axons ‹ ascending visceral sensory axons

Prof. Dr. Nikolai Lazarov 23 Pons Pons – external features ° synonym: pons Varolii ° rostral part of ° basal pons: V shape – "knob-like“ V size: 2 cm long (1543-1575) V composition – transverse fibers ° dorsal pons: V covered by cerebellum V upper half of fourth ventricle ° middle cerebellar peduncle ° functions: V relay station from medulla to higher cortical structures V assists in the control of movements V control of sleep and arousal V contains respiratory center and regulates respiration Prof. Dr. Nikolai Lazarov 24 Pons Pons – anterior aspect

° sulcus basilaris Ù basilar artery ° median eminence Ù corticospinal fibers, ‘pyramidal tract’ ° middle cerebellar peduncle ° trigeminal nerve exit

Prof. Dr. Nikolai Lazarov 25 Pons Pons – dorsal view and tectum

° tectum = superior NB: tectum is Latin for roof , medullary velum tegmentum for covering ° tegmentum = dorsal part of the pons V median sulcus V medial eminence V sulcus limitans V V superior fovea V "the blue spot“ V vestibular area V auditory tubercle V striae medullares

Prof. Dr. Nikolai Lazarov 26 Pons Pontine basis: nuclei pontis

° pontine nuclei – ~20 million neurons: V excitatory glutamatergic neurons V inhibitory GABAergic (5%) neurons ° noradrenergic nuclei – in upper pontine tegmentum: V nucleus coeruleus (A6) V parabrachial nuclei, lateral and medial

Prof. Dr. Nikolai Lazarov 27 Pontine tegmentum: Pons motor cranial nerve triad ° motor nuclei: V trigeminal motor nucleus (V) V abducens nucleus (VI) V facial nucleus (VII) ° internal loop of facial nerve

Prof. Dr. Nikolai Lazarov 28 Pontine tegmentum: Pons sensory cranial nerve nuclei ° trigeminal nuclei (V): V main sensory (pontine) nucleus V mesencephalic trigeminal nucleus V spinal trigeminal nucleus ° cochlear nuclei (VIII): V ventral cochlear nucleus V dorsal cochlear nucleus ° vestibular nuclei (VIII): V superior vestibular nucleus (Bechterew) V inferior vestibular nucleus (Roller) V medial vestibular nucleus (Schwalbe) V lateral vestibular nucleus (Deiters) Ù posterior spinocerebellar tract

Prof. Dr. Nikolai Lazarov 29 Pons Fourth ventricle

° embryonic origin – rhombencephalon ° formation – tentorial space between: V dorsal pons & upper medulla oblongata V cerebellum ° lateral boundaries: V caudal part: ‹ gracile&cuneate tubercles ‹ fasciculus cuneatus ‹ inferior cerebellar peduncle V cranial part: ‹ superior cerebellar peduncle ° roof (dorsal wall): V cranial portion: ‹ superior cerebellar peduncle ‹ V caudal portion: } fastigium ‹ inferior medullary velum ‹ Ù choroid plexuses ° ventral floor – rhomboid fossa ° communication openings: V (of Magendie) Ù central V lateral apertures (of Luschka) canal V (of Sylvius) Ù IIIrd ventricle

Prof. Dr. Nikolai Lazarov 30 Midbrain Midbrain – general features ° location – between forebrain and hindbrain ° the smallest region of the brainstem – 6-7g ° the shortest brainstem segment ~ 2 cm long ° least differentiated brainstem division ° human midbrain is archipallian – shared general architecture with the most ancient of vertebrates ° embryonic origin – mesencephalon ° main functions: V a sort of relay station for sound and visual information V serves as a nerve pathway of the cerebral hemispheres V controls the eye movement V involved in control of body movement

Prof. Dr. Nikolai Lazarov 31 Midbrain Midbrain – gross anatomy ° dorsal part – tectum (quadrigeminal plate): V superior colliculi V inferior colliculi Ù cerebral aqueduct (of Sylvius) ° ventral part – cerebral peduncles: V dorsal – tegmentum (central part) V ventral – cerebral crus Ù substantia nigra

Prof. Dr. Nikolai Lazarov 32 Midbrain Cerebral crus – internal structure ° Cerebral peduncle: V crus cerebri V tegmentum mesencephali V substantia nigra ° two thick semilunar white matter bundles ° composition – somatotopically arranged motor tracts: V corticospinal } pyramidal tracts – medial ⅔ V corticobulbar V corticopontine fibers: ‹ frontopontine tracts – medially ‹ temporopontine tracts – laterally ° interpeduncular fossa (of Tarin ) V posterior perforated substance

Prof. Dr. Nikolai Lazarov 33 Midbrain Midbrain tegmentum – internal structure V crus cerebri V tegmentum mesencephali V substantia nigra ° location: V ventral to the cerebral aqueduct V dorsal to the substantia nigra ° grey matter content: NB: tegmentum is Latin for covering V periaqueductal grey matter V nuclei of cranial nerves III & IV V midbrain reticular formation V red nucleus, nucleus ruber: ‹ parvocellular part – rostral third ‹ magnocellular part – caudal portion V ventral tegmental area

Prof. Dr. Nikolai Lazarov “The Red and the Black” – Stendhal (1830) 34 Midbrain Tectum, quadrigeminal plate

V superior colliculi (Latin, higher hills) V inferior colliculi (lower hills) ° Location: V rostral half of the tectum, beneath the thalamus V brachium of superior colliculus Ù lateral geniculate body V alternate grey and white layers V superior colliculus nucleus V oculomotor nucleus V accessory oculomotor nucleus (of Edinger-Westphal ) ° Functions: V primary integrating center for visual responses V visual coordination of eye and head movements – start reflex

Prof. Dr. Nikolai Lazarov corpora quadrigemina = "quadruplet bodies" 35 Cerebellum Cerebellum – gross anatomy ° Regional location: V posterior cranial fossa, covered by cerebellar tentorium V beneath the occipital lobes of cerebral hemispheres V behind the pons and medulla oblongata V roof of the fourth ventricle ° Connections with brainstem structures (three paired fiber bundles – peduncles): V midbrain – superior cerebellar peduncle (brachium conjunctivum) V pons – middle cerebellar peduncle (brachium pontis ) V medulla – inferior cerebellar peduncle (restiform body ) ° average weight ~130 g (10% of the total brain volume) ° cerebellum:cerebrum = 1:8 (adult); 1:20 (infant) ° more than 50% of all neurons in the brain ° origin: embryonic hindbrain (rhombencephalon) ° major integrative center for the coordination of muscular activity

Prof. Dr. Nikolai Lazarov 36 Cerebellum Cerebellum – divisions ° three sagital subdivisions: V median portion, cerebellar vermis V two lateral parts, cerebellar hemispheres ° three transverse subdivisions (lobes): V anterior lobe V posterior lobe V flocculonodular lobe

Prof. Dr. Nikolai Lazarov 37 Cerebellum Cerebellum – surface topography ° Foliar pattern: V folia cerebelli (transverse leaf-like laminae) ° Cerebellar fissures: V fissura prima – V-shaped V horizontal fissure V pre- and postpyramidal fissure (fissura secunda ) V posterolateral fissure ° Vermis lobules: V superior surface: ‹ lingula ‹ central lobule ‹ monticulus: • culmen • declive ‹ folium vermis V inferior surface: ‹ tuber vermis ‹ pyramid ‹ uvula ‹ nodule

Prof. Dr. Nikolai Lazarov 38 Cerebellum Cerebellum – surface topography

° Hemisphere lobules: V superior surface: ‹ (vinculum lingulae) ‹ alae of the central lobule ‹ anterior quadrangular lobule ‹ lobulus simplex (posterior quadrangular lobule) ‹ superior semilunar lobule V inferior surface: ‹ inferior semilunar lobule ‹ gracile lobule (paramedianus) ‹ biventral lobule ‹ tonsil ‹ flocculus

Prof. Dr. Nikolai Lazarov 39 Cerebellum Phylogenetic and functional divisions

° Archicerebellum: V flocculonodular lobe = flocculus + nodulus (+ part of uvula ) V functionally related to maintenance of balance: vestibulocerebellum ° Paleocerebellum: V anterior lobe = lingula, central lobule, culmen, pyramid, uvula (of vermis) + quadrangular lobules (of cerebellar hemispheres) V regulates body and limb movements, involved in control of muscle tone via the spinal cord: spinocerebellum ° Neocerebellum: V posterior lobe = the rest of cerebellum V most concerned with planning movement and coordination of somatic motor function: cerebrocerebellum (pontocerebellum)

Prof. Dr. Nikolai Lazarov 40 Cerebellum Cerebellum – internal structure ° grey matter: V cerebellar cortex, cortex cerebelli V intracerebellar (deep) nuclei, nuclei cerebelli ° white matter, medullary substance (corpus medullare): V primary laminae – “arbor vitae” (tree of life) V intrinsic fibers, fibrae propriae V projection fibers V myelinated axons of the Purkinje cells V afferent fibers – ‘climbing’ and ‘mossy’

Prof. Dr. Nikolai Lazarov 41 Cerebellum Cerebellar cortex

° Molecular layer, stratum moleculare – 300-400 µm: V outer stellate neurons and basket cells (GABA) V Fañanás glial cells (astrocytes) – feather-like

° Purkinje cell layer, stratum purkinjense: V Purkinje cells V Bergmann glial cells

° Granular layer, stratum granulosum – 100 µm: V granule cells – 10 11 (Glu) V Golgi type II cells (GABA)

Prof. Dr. Nikolai Lazarov 42 Cerebellum Cortical inputs – afferent fibers Vclimbing fibers: ‹ originate from the inferior olivary nucleus ‹ direct excitatory contacts with Purkinje cells Vmossy fibers: ‹ excitatory synaptic contacts with granule cells ‹ rosettes Ù cerebellar glomerulus

Prof. Dr. Nikolai Lazarov 43 Cerebellum Deep cerebellar nuclei

° Dentate nucleus , nucleus dentatus ° Interpositus nucleus: V emboliform nucleus, nucleus emboliformis V globose nucleus, nucleus globosus ° Fastigial nucleus, nucleus fastigii

Prof. Dr. Nikolai Lazarov 44 Diencephalon Diencephalon – gross structure and parts

Prof. Dr. Nikolai Lazarov 45 Thalamus Thalamus – external features ° two egg-shaped lobes of grey matter Vthird ventricle medially Gr. θάλαμος = room, chamber Vhypothalamus Ùhypothalamic sulcus

° Thalamus dorsalis: V rostral pole = tuberculum anterius ° nuclear complex – 2% of the total brain thalami Vabout 80% V caudal pole = pulvinar thalami of diencephalic mass (“ cushioned seat ”) ‹~30 mm long V interthalamic adhesion ‹~20 mm wide V lamina affixa ‹~20 mm tall V thalami

Prof. Dr. Nikolai Lazarov 46 Thalamus Thalamus – internal structure

° internal medullary lamina Ù three major nuclear masses: (medial) – Y-shaped: V anterior V medial V lateral nuclear groups

° external medullary lamina (lateral): Ù reticular nucleus of the thalamus

Prof. Dr. Nikolai Lazarov 47 Metathalamus Metathalamus – geniculate bodies

° Medial geniculate body: subcortical acoustic center (thalamic relay) V inferior colliculi Ù inferior brachium Ù acoustic radiation Ù auditory cortex

° Lateral geniculate body: primary processing center for visual information V superior colliculi Ù brachium of superior colliculus Ù optic radiation Ù visual (striate) cortex

Prof. Dr. Nikolai Lazarov 48 Epithalamus Epithalamus

° stria medullaris thalami ° habenular trigone: V habenular nuclei, medial and lateral ° habenula V habenular commissure ° , corpus pineale (epiphysis) ° V subfornical organ (circumventricular organs)

Prof. Dr. Nikolai Lazarov 49 Subthalamus Subthalamus (ventral thalamus)

° subthalamic nucleus (corpus Luysi ): basal ganglia V contralateral hemiballismus ° zona incerta ° nuclei reticulares ° nuclei campi perizonales (H1- and Н2-fields of Forel)

Prof. Dr. Nikolai Lazarov 50 Hypothalamus Hypothalamus – gross anatomy

Gr. ὑποθαλαμος = hypo-, cognate to Latin sub- "under" V most ventral portion of the diencephalon V weight 4-5 g – less than 1% of the total volume ° preoptic area, area preoptica ° optic chiasm, chiasma opticum ° tuber cinereum, median eminence ° infundibular tract, infundibulum Ù hypophysis cerebri ° mammillary bodies, corpora mammillaria

Prof. Dr. Nikolai Lazarov 51 Hypothalamus Hypothalamus – functional significance ° 0.5% of the total volume of human brain ° main function – homeostasis (maintaining the body's status quo) ° central control of: V visceral functions V endocrine effects – release/inhibiting factors ° neurosecretion: V pituitary hormones – oxytocin, vasopressin ° temperature regulation – dual thermostat ° instinctive and cyclic behaviors: V regulation of food (appetite ) and water intake V control of sexual behavior and reproduction V biological clock (sleep-waking cycle) V expression of emotion, fear, rage, aversion, pleasure and reward

Prof. Dr. Nikolai Lazarov 52 Diencephalon

° embryonic origin – prosencephalon ° location – between the two thalami (lateral walls) and hypothalamus

Prof. Dr. Nikolai Lazarov 53 Diencephalon Third ventricle ° anterior boundary – lamina terminalis ° posterior boundary – posterior commissure V pineal recess Ù pineal gland V cerebral aqueduct ° floor – parts of the hypothalamus V V infundibular recess ° roof – layer of ependyma, covered by the tela choroidea ventriculi tertii Ù choroid plexus of the third ventricle ° communication with: V fourth ventricle – cerebral aqueduct (of Sylvius ) V – interventricular foramina (of Monro )

Prof. Dr. Nikolai Lazarov 54 Reticular formation Reticular formation – terminology

NB: reticulum means netlike structure Why is the reticular formation Because their fibers indeed a reticular formation? build a net.

Prof. Dr. Nikolai Lazarov 55 Reticular formation Reticular formation – nuclei

° Median column of reticular nuclei – raphe nuclei (serotonergic): V nucleus raphes obscurus et pallidus in medulla V nucleus raphes magnus in pons V nucleus raphes centralis superior and V nucleus raphes dorsalis in midbrain ° Medial column: V medullary gigantocellular (magnocellular) nucleus V pontine gigantocellular nucleus V nucleus tegmenti pontis V nucleus pontis caudalis V nucleus pontis oralis V nucleus cuneiformis V nucleus subcuneiformis ° Lateral column – parvocellular : V nucleus pontis centralis V nuclei parabrachiales V nucleus tegmentalis pedunculopontinus

Prof. Dr. Nikolai Lazarov 56 Reticular formation Reticular formation – functions

° controls ~25 specific behaviors: V sleep V walking V eating V urination&defecation V sexual activity ° additional functions: V arousal V attention V cardiac reflexes V motor functions V regulates awareness V relays nerve signals to the cerebral cortex ° one of the phylogenetically oldest portions of the brain

Prof. Dr. Nikolai Lazarov 57 Telencephalon Cerebrum – general overview ° weight ~ 1100 g ° 80% of the total brain mass ° cerebral hemispheres: V pallium ‹superficial grey matter (cerebral cortex) ‹deep grey matter (basal ganglia) ‹white matter ‹ventricular cavity (lateral ventricle) V longitudinal fissure of the cerebrum: ‹falx cerebri ‹corpus callosum

Prof. Dr. Nikolai Lazarov 58 Telencephalon Cerebral hemispheres ° three surfaces: V superolateral (convex) V medial (flat and vertical) V inferior (irregular): ° six lobes: ‹orbital part V frontal lobe V parietal lobe ‹tentorial part V occipital lobe V temporal lobe V insular lobe ° main sulci: V limbic lobe V central sulcus (of Rolando ) V lateral sulcus (of Sylvius ) V parietooccipital sulcus V cingulate sulcus Ù collateral sulcus

Prof. Dr. Nikolai Lazarov NB: sulcus (Latin: "furrow", pl. sulci ) 59 Telencephalon Cerebral cortex

V surface area : approx. 2200-2850 cm2 V thickness: ‹ 1.5 mm – frontal and temporal poles ‹ 5 mm – in the precentral gyrus V total number of cortical neurons: V 2.6-20 billion

V 0.6x10 9 synapses per mm3 V 60000 synapses over one pyramidal neuron V one pyramidal nerve cell – 600 neurons

NB: The human brain contains roughly 90 billion neurons, Prof. Dr. Nikolai Lazarov which transmit information across roughly 150 trillion synapses ! 60 Telencephalon Cortical cell types ° pyramidal cells – 66% of the total neocortical cell population (glutamate- and aspartatergic) V small-sized (10-15 µm) V medium-sized (20-40 µm) V large-sized (50-80 µm) V giant pyramidal cells of Betz (80-120 µm) – in the precentral gyrus (motor cortex) ° stellate (granule) cells – 33% of the total neocortical population (Golgi type II cells) V small in size (8-14 µm) – interneurons (GABA, VIP, SP, CCK, ENK) ‹ horizontal cells of Cajal – small and fusiform; in the most superficial cortical layer ‹ fusiform cells – “modified pyramidal cells ”; spindle-shaped, in the deepest cortical layer ‹ cells of Martinotti – small and multipolar; in practically all cortical layers ‹ basket cells – horizontally extended ‹ neurogliaform stellate cells – small in size ° pleomorphic cells – modified pyramidal cells; – large-sized and varying in shape, in the deepest layer

Prof. Dr. Nikolai Lazarov 61 Telencephalon Cytoarchitectonic mapping

° neocortex (Latin for "new bark" or "new rind") – 6-layered; neopallium ("new mantel") – 90% of hemispheric surface isocortex (Greek isos = "equal rind"); phylogenetically newer part of the cortex ° allocortex, archipallium – the older, original part of the cerebral cortex; (Gr. allos = “different, other, another”) ; fewer than six layers – 3- or 4-layered: V paleocortex, paleopallium – 1% of the cerebral cortex (Gr. palaios = "ancient, old“); 4-layered, Ù olfactory cortex (rhinencephalon) V archaeocortex, archipallium – 3-4% of the cortex (Gr. arche = “beginning”); 3-layered, Ù hippocampal cortex ° mesocortex – intermediate in form between the allocortex and the isocortex ; 5-6-layered, Ù cingulate gyrus Prof. Dr. Nikolai Lazarov 62 Telencephalon Laminar pattern in the cerebral cortex

Cortical layers ( Brodmann ): ° Meynert – 5 layers (laminae) I. Molecular layer ° B. Lewis – 6 layers (plexiform lamina) II. External granular lamina III. External pyramidal lamina IV. Internal granular lamina V. Internal pyramidal (ganglionic) lamina VI. Multiform (fusiform) lamina

Prof. Dr. Nikolai Lazarov 63 Telencephalon Myeloarchitecture: cortical fiber structure

° Flechsig – 35 myelogenic areas ° C. and O. Vogt – 400 areas ° stria laminae molecularis (plexiformis), (plexus of Exner ) ° stria laminae granularis externa е (band of Bechterew ) ° stria laminae granularis interna е (external band of Baillarger, or band of Gennari ) ‹ in sulcus calcarinus (area striata – band of Vicq d’Azyr) ° stria laminae pyramidalis interna е (ganglionaris), (internal band of Baillarger )

Prof. Dr. Nikolai Lazarov 64 Telencephalon Cerebrum – white matter

° Three vast fiber systems:

V association fibers – fibrae associationes telencephali

V commissural fibers – fibrae commissurales telencephali

V projection fibers – fibrae projectiones telencephali

Prof. Dr. Nikolai Lazarov 65 Telencephalon Corpus callosum

° broad, thick plate of myelinated fibers ~ 10 cm in length

Vrostrum corporis callosi

Vgenu corporis callosi

Vtruncus corporis callosi

Vsplenium corporis callosi

Vforceps minor (frontal)

Vforceps major (occipital)

Vindusium griseum – limbic system

‹stria longitudinalis medialis (Lancisii )

‹stria longitudinalis lateralis

Prof. Dr. Nikolai Lazarov 66 Telencephalon Projection fibers ° internal capsule: V anterior limb – 1.5 cm ‹ radiatio thalami anterior ‹ tractus frontopontinus (of Arnold ) ‹ fibrae corticostriatae V genu capsulae internae ‹ fibrae corticonucleares V posterior limb: ‹thalamolentiform part • fibrae corticospinales • fibrae corticorubrales • fibrae corticoreticulares ‹retrolentiform part • radiatio thalami posterior • tractus parietooccipitopontinus ‹sublentiform part • radiatio optica (tract of Gratiolet ) • radiatio acustica • fibrae corticotectales • fibrae temporopontinae (tract of Türk )

Prof. Dr. Nikolai Lazarov 67 Telencephalon Basal nuclei (“Basal ganglia”)

° Classically: V nucleus caudatus V nucleus lentiformis V claustrum V corpus amygdaloideum – limbic system

° The International Basal Ganglia Society: V nucleus caudatus V nucleus lentiformis V nucleus subthalamicus V substantia nigra

Prof. Dr. Nikolai Lazarov 68 Telencephalon Caudate nucleus

° arcuate mass of grey matter ° length ~ 7 сm ° parts: V head (caput nuclei caudati) V body (corpus nuclei caudati) V tail (cauda nuclei caudati)

Prof. Dr. Nikolai Lazarov 69 Telencephalon Lentiform nucleus

° putamen + nucleus caudatus = striatum (neostriatum) ° globus pallidus = pallidum (palleostriatum): V globus pallidus lateralis (pallidum externum) V globus pallidus medialis (pallidum internum)

Prof. Dr. Nikolai Lazarov 70 Telencephalon Lateral ventricle

V Left lateral ventricle – first ventricle? V Right lateral ventricle – second ventricle? NB: Since they are symmetric, a numbering system was not used for the lateral ventricles !

Prof. Dr. Nikolai Lazarov 71 Telencephalon Lateral ventricle ° embryonic origin – prosencephalon ° arched-shaped – general shape of hemispheres ° parts: V anterior horn (cornu) ~3 cm; triangular shape into the frontal lobe Ù V central part ~4 cm; into the parietal lobe; collateral trigone V posterior horn (cornu) – 1.2-2 cm; into the occipital lobe Ù V inferior horn (cornu) – 3-4 cm; into the temporal lobe Ù ; collateral eminence ° composition – cerebrospinal fluid: V plexus choroideus ventriculi lateralis – missed in the anterior and posterior horns ° communication with: V third ventricle – interventricular foramina (of Monro )

Prof. Dr. Nikolai Lazarov 72 Telencephalon Limbic system

° Papez circuit, 1937: V a route the limbic system communicates between the hippocampus, thalamus, hypothalamus, and cortex ° Functions – cortical control of: V long-term memory Jamez Papez ° Limbic system: (1883-1958) Lat. limbus = "border“, "belt“ V learning V emotions ° paleopallium (old mammalian) brain ° cortical structures – limbic lobe ° subcortical nuclei: V hippocampal formation and fornix V amygdaloid nuclear complex V septal nuclei V hypothalamus, epithalamus V various thalamic nuclei V part of the basal ganglia

Prof. Dr. Nikolai Lazarov 73 Telencephalon Hippocampal formation

° Hippocampus, seahorse: Gr. ιππος , hippos = horse, καμπος , kampos = sea monster ° location – inside the medial temporal lobe ° three major regions: V hippocampus proper (Ammon’s horn) – CA1-CA4 fields of Lorente de Nó V dentate gyrus ‹ three-layered cortices V subiculum – transition zone ° hippocampal functions : V behavioral inhibition (anxiety) V learning and recent memory V spatial coding

Prof. Dr. Nikolai Lazarov 74 Telencephalon Fornix ° Fornix, Lat. = “vault”, “arch” V C-shaped bundle of fibres (axons) V the sole efferent system V carries signals from the hippocampus to the mammillary bodies and septal nuclei ° Structure: V crus of the fornix V body of the fornix V (hippocampal) commissure V anterior fibers, "precommissural fornix" Ù the septal nuclei and nucleus accumbens V posterior fibres, "postcommissural fornix“ (column of the fornix) Ù the mammillary bodies Prof. Dr. Nikolai Lazarov 75 Telencephalon Amygdala (amygdaloid nuclear complex)

° Lat. corpus amygdaloideum Gr. αμυγδαλή , amygdal ē, “almond”, “tonsil” ° Location – deep within the medial temporal lobes ° Amygdala nuclei: V corticomedial nuclear group – basal ganglia V basolateral nuclear group: ‹ lateral amygdaloid nucleus ‹ basal amygdaloid nucleus ‹ accessory basal amygdaloid nucleus V central nucleus, medial and lateral ° Functions: V fear reactivity and other emotional functions V feeding V sexual behavior

Prof. Dr. Nikolai Lazarov 76 Telencephalon Localization of cerebral functions

Michelangelo’s Creation of Adam Meshberger’s interpretation (1508-1512) JAMA 264:1837-1841, 1990

Prof. Dr. Nikolai Lazarov 77 Telencephalon Functional differentiation of the cerebral cortex

° Main cortical areas: V Sensory areas Û afferent projections V Motor areas Ù efferent projections V Associational (‘silent’) areas V ‘Visuopsychic’ cortex

Prof. Dr. Nikolai Lazarov 78 Telencephalon Cerebral asymmetry (hemispheric dominance)

° Left hemisphere : ° Right hemisphere : V verbal V almost non-verbal V linguistic description V musical V mathematical V geometrical V sequential V spatial comprehension V analytical V temporal synthesis V direct link to ‘consciousness’ V link to ‘consciousness’?

Roger W. Sperry – ‘’split-brain” Nobel Prize in Medicine or Physiology 1981 "for his discoveries Prof. Dr. Nikolai Lazarov concerning the functional specialization of the cerebral hemispheres" 79 Sex differences in the cerebrum

Prof. Dr. Nikolai Lazarov 80 Thank you…

Prof. Dr. Nikolai Lazarov 81