DiencephalonDiencephalon ((““inin --betweenbetween brainbrain ””))

33rdrd VentricleVentricle CNSCNS divisionsdivisions DirectionalDirectional termsterms –– forebrainforebrain levellevel

– regional organization

 (dorsalis) – topographic and nuclear organization (Gr. thalamos , “inner chamber”))  Metathalamus – the geniculate bodies  – and  (thalamus ventralis)  – divisions, nuclei and connections TheThe DiencephalonDiencephalon TheThe DiencephalonDiencephalon

THALAMUS EPITHALAMUS

SUBTHALAMUS HYPOTHALAMUS TheThe Adhesio Interthalamica DiencephalonDiencephalon

Pineal Gland

Hypothal Sulcus Anterior Commissure Lamina Terminalis Infundibulum DiencephalonDiencephalon

dorsaldorsal surfacesurface DiencephalonDiencephalon –– superiorsuperior dorsaldorsal viewview

anterior tubercle 3rd ventricle DiencephalonDiencephalon –– laterallateral dorsaldorsal viewview DiencephalonDiencephalon

ventralventral surfacesurface MetathalamusMetathalamus

Pulvinar

Lateral Geniculate

Medial Geniculate BordersBorders ofof thalamusthalamus

Lat. ventricle 3rd Ventricle Int.capsule BordersBorders ofof thalamusthalamus

Posterior commissure Fornix

Hypothalamic sulcus

Lamina terminalis

Thalamus OriginOrigin ofof CNSCNS subdivisionssubdivisions SecondarySecondary vesiclesvesicles DiencephalonDiencephalon isis largerlarger duringduring brainbrain developmentdevelopment thanthan inin postnatalpostnatal brainbrain

Neural tube folding (5 th -8th wk) DiencephalicDiencephalic developmentdevelopment The diencephalon consists of roof and alar plates but lacks the basal and floor plates

Lateral ventricle

 Alar plate → thalamus, hypothalamus, neurohypophysis, and infundibulum  Roof plate → epiphysis, and the posterior commissure AlarAlar vs.vs. BasalBasal inin forebrainforebrain

DiencephalicDiencephalic developmentdevelopment

Embryonic Adult brain ThalamocorticalThalamocortical axonsaxons passpass throughthrough thethe ventralventral telencephalontelencephalon (VT)(VT) andand futurefuture basalbasal gangliaganglia (GP/STR)(GP/STR) beforebefore theythey reachreach thethe cortexcortex EstimatedEstimated timetime ofof developmentdevelopment ofof variousvarious brainbrain regiregionsons

2 mo 6 mo

Modified from Bayer SA et al. Neurotoxicology 14:83–144, 1993 General organization of the thalamus

 Nuclear groups   Internal medullary lamina  External medullary lamina

Reticular nucleus Internal External medullary medullary lamina lamina Midline nuclei ThalamicThalamic nucleinuclei formform nuclearnuclear groupsgroups

I. Lateral Group II. Medial Group III. Anterior Group metathalamus IV. Posterior Group V. Intralaminar Group VI. Reticular nucleus ThalamusThalamus –– sectionsection atat anterioranterior levellevel

LV LV

3v

reticular

internal medullary lamina ThalamusThalamus –– sectionsection atat midmid --levellevel

LV LV

3v

reticular

internal medullary lamina ThalamusThalamus –– sectionsection atat posteriorposterior levellevel

LV LV

3v

reticular

internal medullary lamina TThalamushalamus isis thethe criticalcritical relayrelay forfor thethe flowflow ofof sensorysensory informationinformation toto thethe neocortexneocortex

Cortex

Motor pathway Sensory pathway ThalamusThalamus isis moremore thanthan simplysimply aa relayrelay !!

ItIt actsacts asas aa gatekeepergatekeeper forfor informationinformation toto thethe cerebralcerebral cortex,cortex, preventingpreventing oror enhancingenhancing thethe passagepassage ofof specificspecific informationinformation dependingdepending onon thethe behavioralbehavioral statestate ThalamicThalamic nucleinuclei –– laterallateral groupgroup

  ventral posterolateral nucleus (VPL)  ventral posteromedial nucleus (VPM)  ventral posteroinferior nucleus (VPI)  ventral lateral nucleus (VL)  (VA) I. Lateral Group  Dorsal nuclear group II. Medial Group  Lateral dorsal nucleus (LD) III. Anterior Group  Lateral posterior nucleus (LP) IV. Posterior Group  Pulvinar -lateral posterior complex V. Intralaminar Group VI. Reticular nucleus ConnectionsConnections ofof thethe laterallateral thalamicthalamic nucleinuclei VentralVentralNuclearNuclear GroupGroup

Cortex

SMA - supplementary motor area MI (M1) – PM – SI (S1) – primary somatosensory cortex

SomatosensorySomatosensory mapmap (( somatotopicsomatotopic organization)organization) inin VPLVPL && VPMVPM

VPL

+taste fibers

VPM ConnectionsConnections ofof thethe laterallateral thalamicthalamic nucleinuclei DorsalDorsal NuclearNuclear GroupGroup

y y

Pulvinar

ThalamicThalamic nucleinuclei –– medialmedial groupgroup

 Mid DorsomedialDorsomedial NucleusNucleus (MD)(MD)  pars magnocellularis (MDmc)  pars parvocellularis (MDpc)  pars paralaminaris (MDpl )  I. Lateral Group MidlineMidline NuclearNuclear GroupGroup ((poorlypoorly developeddeveloped inin humans)humans) II. Medial Group  paratenial nucleus III. Anterior Group  reunience nucleus IV. Posterior Group  submedial nucleus V. Intralaminar Group  rhomboid nucleus VI. Reticular nucleus MidlineMidline thalamicthalamic nucleinuclei

Interthalamic adhesion

Midline nuclei ThalamicThalamic nucleinuclei –– anterioranterior && posteriorposterior groupsgroups

Mid  AnteriorAnterior NuclearNuclear GroupGroup  anteroventral nucleus (AV)  anterodorsal nucleus (AD)  anteromedial nucleus (AM)

I. Lateral Group  PosteriorPosterior NuclearNuclear GroupGroup II. Medial Group (medial(medial toto thethe Pulvinar,Pulvinar, III. Anterior Group mergemerge withwith MGB)MGB)  IV. Posterior Group suprageniculate nucleus  nucleus limitans V. Intralaminar Group nucleus limitans  posterior nucleus VI. Reticular nucleus ConnectionsConnections ofof thethe thalamicthalamic nucleinuclei MedialMedial && AnteriorAnterior NucleiNuclei

y y y

y ThalamicThalamic nucleinuclei –– intralaminarintralaminar groupgroup

 Caudal Nuclear Group (most important in humans ) Mid  centromedian nucle us  parafascicular nucle us  Rostral Nuclear Group  paracentral I. Lateral Group  centrolateral II. Medial Group  centromedial III. Anterior Group IV. Posterior Group V. Intralaminar Group VI. Reticular nucleus Afferent Efferent ConnectionsConnections ofof thethe thalamicthalamic intralaminarintralaminar nucleinuclei

 ReceiveReceive fromfrom manymany subcorticalsubcortical andand corticalcortical areasareas  ProjectProject toto  other thalamic nuclei  cortex  (t he projection is topographically organized : → ; parafascicular nucleus → caudate )

Intralaminar & midline nuclei are non-specific thalamic nuclei ThalamicThalamic nucleinuclei –– reticularreticular nucleusnucleus

 A continuation of the of the brain stem into the diencephalon  Unique among thalamic nuclei !!! its do not leave the thalamus  Receives collaterals of corticothalamic projections and thalamocortical

I. Lateral Group projections II. Medial Group  Sends to other thalamic nuclei III. Anterior Group  GABAergic (inhibitory) → plays a role IV. Posterior Group in integrating and gating activities of V. Intralaminar Group thalamic nuclei VI. Reticular nucleus Tricorn MetathalamusMetathalamus Shape

Pulvinar

Medial Geniculate

Lateral Geniculate MetathalamicMetathalamic nucleinuclei

 MedialMedial GeniculateGeniculate NucleusNucleus (MG)(MG)  ventralventral oror principalprincipal nucleusnucleus  dorsaldorsal nucleusnucleus  medialmedial nucleusnucleus  LateralLateral GeniculateGeniculate NucleusNucleus (LG)(LG)  dorsaldorsal nucleusnucleus (LGd)(LGd)  ventralventral nucleusnucleus (LGv)(LGv) LateralLateral GeniculateGeniculate NucleusNucleus (LGd)(LGd) →→ VisualVisual PathwayPathway

Dorsal Nucleus (LGd)

dorsolateral Magnocellular Part 1, 2 Parvocellular Part 3, 4, 5, 6 contralateral afferents 1, 4, 6 ipsilateral afferents 2, 3, 5

ventromedial Ventral Nucleus ( LGv ) part of thalamic reticular nucleus VisualVisual PathwayPathway

1. 2. Optic chiasm 3. Optic tract 4. Lateral geniculate body 5. 6. Visual cortex VisualVisual pathwaypathway viavia LGNLGN

loops Ocular dominance columns in primary visual cortex (V1)

C I I C

I = from ipsilateral C = from contralateral retina OverviewOverview ofof thalamicthalamic connectivityconnectivity

AN = Anterior nn. LD = Lateral dorsal n. LP = Lateral posterior n. Pul = Pulvinar DM = Dorsomedial n. Mid = Midline nn. VA = Ventral anterior n. VL = Ventral lateral n. VPL = Ventral posterolateral n. VPM = Ventral posteromedial n. LGB = Lateral geniculate body MGB = Medial geniculate body IL = Intralaminar nn. CM = Centromedian n. SummarySummary ofof thethe connectionsconnections ofof thethe thalamicthalamic nucleinuclei

Specific nuclei (sensory or motor) Association nuclei (sensory or motor

Non-specific nuclei OverviewOverview ofof majormajor functionsfunctions thalamicthalamic nucleinuclei

non- specific limbic autonomic motor

somatosensory R taste

visual internal regulator higher visual auditory ThalamicThalamic radiationsradiations = fibers which reciprocally connect the thalamus & cortex via the internal capsule

EpithalamusEpithalamus && subthalamussubthalamus SubthalamusSubthalamus  BasalBasal GangliaGanglia

 SubthalamicSubthalamic nucleusnucleus  ZonaZona incertaincerta  FieldsFields ofof ForelForel SubthalamusSubthalamus SubthalamusSubthalamus Red Nucleus Subthalamus

• Location: diencephalic- mesencephalic border • Abuts the posterior limb of the internal capsule • Shaped like a lens

Substantia Nigra

Internal Capsule (posterior limb) ConnectionsConnections ofof subthalamussubthalamus

Afferent Efferent (fiber bundles containing efferents to the thalamus ))

HH prerubralprerubral fieldfield H1H1 thalamicthalamic fasciculusfasciculus H2H2 lenticularlenticular fasciculusfasciculus

H = “Haube ” (German, cap) The connections of are connections of the

A lesion in the contralateral subthalamic nucleus leads to hemiballismus → violent flinging involuntary movements of one side of the body.

Kandel, Schwartz, Jessell; Principles of Neural Science, 4 th ed. ZonaZona incertaincerta (zone(zone ““inin betweenbetween ””))

 Rostral continuation of the mesencephalic reticular formation that extends laterally into the reticular nucleus of the thalamus  Involved in control of movement – its stimulation has been shown to suppress limb tremor (has GABA ergic )  Has reciprocal connections with neocortex, thalamus, brain stem, basal ganglia, , hypothalamus, basal , and Limbic System Limbic       medial lateral medial lateral     Habenular nuclei Habenular Pinealgland Habenular nuclei Habenular commissure Habenular Pinealgland      

Epithalamus Epithalamus Epithalamus Habenular Epithalamus commissure Epithalamus (roof of pineal recess) Pineal gland (secretes )

Posterior commissure (eye movements and light reflex) EpithalamusEpithalamus

3rd Ventricle EpiphysisEpiphysis ((pinealpineal glandgland ))

 PinealocytesPinealocytes –– secretesecrete melatoninmelatonin  nightnight ↑↑//dayday ↓↓  otherother hormoneshormones  thyrotropin -releasing (TRH)  leuteinizing hormone –releasing hormone (LHRH)  –release inhibitory factor (SRIF)  InterstitialInterstitial cellscells –– glialglial --likelike  BloodBlood vesselsvessels TheThe pinealpineal glandgland cc alcifiesalcifies afterafter thethe ageage ofof 1616 years.years. ThisThis factfact isis usedused inin thethe detectiondetection ofof midlinemidline shiftsshifts inin skullskull xx --raysrays →→ inin casecase ofof aa spacespace --occupyingoccupying lesionlesion displacingdisplacing thethe pinealpineal ..

Pineal gland (calcified) PinealPineal glandgland

neuroglia

acervulus (brain sand) PinealPineal glandgland saggital section

Posterior Commissure

cross-section HabenulaHabenula (Latin(Latin diminutivediminutive ofof habena,habena, ““aa smallsmall strapstrap oror reinrein ””))

 Receive the stria medullaris thalami – from septal (medial olfactory) area in frontal lobe  Project habenulo -interpeduncular tract (fasciculus retroflexus of Meynert) to the interpeduncular nucleus of the  The two habenular nuclei are connected by the habenular commissure  Involved in limbic system – and behavior ConnectionsConnections ofof habenularhabenular nucleinuclei

Septal nuclei BloodBlood supplysupply toto thalamusthalamus

medial territory

lateral territory BloodBlood supplysupply toto thalamusthalamus

 BBasilarasilar rootroot ofof thethe posteriorposterior cerebralcerebral a.a. →→ paramedianparamedian branchesbranches (medial(medial territory)territory)  PPosteriorosterior cerebralcerebral arteryartery →→ geniculothalamicgeniculothalamic branchbranch ((posterolateralposterolateral territoryterritory ))  PPosteriorosterior communicatingcommunicating arteryartery →→ tuberothalamictuberothalamic branchbranch ((anterolateralanterolateral territoryterritory ))  IInternalnternal carotidcarotid arteryartery →→ anterioranterior choroidalchoroidal branchbranch (lateral(lateral territory)territory) IntracerebralIntracerebral hemorrhagehemorrhage DejerineDejerine --RoussyRoussy syndromesyndrome

 PosteiorPosteior cerebralcerebral arteryartery suppliessupplies VPL,VPL, VPM,VPM, MG,MG, LGLG ,, pulvinarpulvinar  PCAPCA infarctinfarct →→ DejerineDejerine --RoussyRoussy syndromesyndrome  PurePure hemisensoryhemisensory lossloss ++ nono hemiparesishemiparesis VenousVenous drainagedrainage ofof thalamusthalamus →→ vv.vv. profundaeprofundae cerebricerebri HypothalamusHypothalamus

4 cm 3 of neural tissue, 0.3% of the total brain

3rd Ventricle HypothalamusHypothalamus –– ventralventral viewview HypothalamusHypothalamus –– ventralventral viewview (landmarks)(landmarks)

Optic Chiasm

Infundibulum

Mammillary Bodies BordersBorders ofof hypothalamushypothalamus

Hypothal Sulcus

Midbrain Interpeduncular fossa Lamina Terminalis Optic Chiasm TheThe hypothalamushypothalamus servesserves thisthis integrativeintegrative functionfunction bbyy regulationregulation ofof 55 basicbasic physiologicalphysiological needsneeds

 It controls blood pressure and electrolyte composition by a set of regulatory mechanisms that range from control of drinking and salt appetite to the maintenance of blood osmolality and vasomotor tone  It regulates body temperature by means of activities ranging from control of metabolic thermogenesis to behaviors such as seeking a warmer or cooler environment  It controls energy metabolism by regulating feeding, digestion, and metabolic rate  It regulates reproduction through hormonal control of mating, pregnancy, and  It controls emergency responses to stress , including physical and immunological responses to stress by regulating blood flow to muscle and other tissues and the secretion of adrenal stress FFornixornix dividesdivides thethe hypothalamushypothalamus intointo medialmedial andand laterallateral regionsregions /zones/zones

 MedialMedial –– aa clustercluster ofof nucleinuclei organizedorganized into:into:  ppreopticreoptic nuclearnuclear groupgroup  ssuprachiasmaticuprachiasmatic (supraoptic(supraoptic ;; anterior)anterior) groupgroup  ttuberaluberal (intermediate)(intermediate) nuclearnuclear groupgroup  mmamillaryamillary (posterior)(posterior) nuclearnuclear groupgroup  LateralLateral  medialmedial forebrainforebrain bundlebundle (axons)(axons)  laterallateral hypothalamichypothalamic areaarea (neurons)(neurons) RRegionsegions ofof thethe medialmedial hypothalamushypothalamus

 

  MMedialedial hypothalamushypothalamus –– preopticpreoptic regionregion

 Just caudal to the lamina terminalis  Nuclei  preoptic nuclei (continuous with one of the circumventricular organs - organum vasculosum laminae terminalis, OVLT; receive hormonal inputs)  medial – GnRH → (reproduction & sexual )  lateral – sleep and wakefulness (damage → insomnia)  preoptic periventricular nucleus → part of the parvocellular neurosecretory system MMedialedial hypothalamushypothalamus – ssuprachiasmaticuprachiasmatic (supraoptic(supraoptic ;; anterior)anterior) regionregion

 → ADH secretion into neurophypophysis → retention of water in kidneys (; polydipsia, polyuria); (part of magnocellular system)  Paraventricular nucleus → secretion → contraction of uterine smooth musculature during labour and promot ion of milk ejection (part of magnocellular system)  Anterior nucleus – center → tumors lead to refusal of patients to drink despite severe dehydration  (poorly developed in humans ) - circadian rhythm cross-section regulator ( sleep -wake /day -night cycle s) → receives bilaterally from retina; projects to tuberal hypothalamic nculei (VIP -ergic 3V fibers); influences pineal gland via sympathetic fibers (C8 -T1 level of spinal cord) → melatonin secretion TheThe paraventricularparaventricular nucleusnucleus containscontains 33 distinctdistinct cellcell populationspopulations

  

Anterior pituitary MMedialedial hypothalamushypothalamus –– ttuberaluberal (intermediate)(intermediate) regionregion

 Ventromedial nucleus - satiety center (lesions lead to ↑ appetite & obesity); receives from via  Dorsomedial nucleus – TRH release; n euroendocrine control of catecholamines (projects to spinal cord autonomic neurons)   control of anterior pituitary via tubero - infundibular tract and the hypophyseal portal system (parvocellular system): ACTH, dopamine, β-LPH , β- Fornix Endorphin 3V  major target of actions regulating food intake by acting on food promoting (orexinergic) and food inhibiting (anorexinergic) arcuate neurons MagnocellularMagnocellular vsvs parvocellularparvocellular neurosecretoryneurosecretory systemssystems

tuberoinfundibular tract

Hypothalamus → Hypothalamus → portal blood system → (neurohypophysis) anterior pituitary (adenohypophysis) Information flow between brain and

arcuate n. – PIH parvocellular paraventricular n. periventricular, ventromedial, periventricular & arcuate periventricular n. – GIH dorsomedial nuclei nuclei arcuate n. – GRH pituitary TSH = PRH

Dopamine MMedialedial hypothalamushypothalamus –– mammilarymammilary (posterior)(posterior) regionregion

 Mamillary nuclei  medial (large) – receives from via fornix and sends to anterior thalamus via mamillothalamic tract (MMT) → involved in memory  lateral (small) - descending projection to the midbrain and , the mammillotegmental tract (reticular formation)  tuberomammillary nucleus (histaminergic) – widespread projections to cortex → maintain s arousal (antihistamine drugs cause drowsiness) 3V  Posterior nucleus - the main source of descending hypothalamic fibers to the brain stem : dorsal longitudinal fasciculus MTT

Tuberomammilary n. TheThe fornixfornix

Hippocampus → mammillary medial nucleus HypothalamusHypothalamus -- MammillothalamicMammillothalamic tracttract ((ofof VicqVicq d'Azyrd'Azyr ))

ANTERIOR NUCLEUS

Mamillothalamic tract

MAMMILLARY BODY

Mammillary medial nucleus → anterior thalamic nuclei DorsalDorsal longitudinallongitudinal fasciculusfasciculus –– integrationintegration ofof hypothalamichypothalamic && autonomicautonomic functionfunction

Posterior nucleus LateralLateral regionregion ofof hypothalamushypothalamus

 LiesLies laterallateral toto thethe fornixfornix andand mamillothalamicmamillothalamic tracttract  TheThe medialmedial forebrainforebrain bundlebundle connectsconnects thethe hypothalamushypothalamus withwith thethe septalseptal areaarea ,, cortex,cortex, amygdalaamygdala rostrallyrostrally andand brainbrain stemstem reticularreticular formationformation caudalcaudallyly  LateralLateral hypothalamichypothalamic areaarea  contains orexin (hypocretin) -ergic neurons → stimulate food intake; inhibit anorexigenic neurons in ventromedial nucleus and exite orexigenic neurons in arcuate nucleus  controls activities of monoaminergic and cholinergic systems affecting sleep → destruction is associated with the sleep disorder of narcolepsy MedialMedial && laterallateral hypothalamichypothalamic nuclearnuclear groupsgroups

HypothalamusHypothalamus  LimbicLimbic SystemSystem

Interthalamic adhesion

Tuber cinereum

Infundibulum Optic nerve AfferentsAfferents toto thethe hypothalamushypothalamus

(amygdala)

(amygdala) AfferentsAfferents toto hypothalamushypothalamus

To reticular formation

Posterior nucleus

Medial forebrain bundle EfferentsEfferents fromfrom hypothalamushypothalamus EndocrineEndocrine pathwayspathways –– posteriorposterior pituitarypituitary EndocrineEndocrine pathwayspathways –– anterioranterior pituitarypituitary FunctionsFunctions ofof hypothalamichypothalamic nucleinuclei Nucleus Key functions Preoptic nuclei: Medial Parvocellular hormone control Lateral Sleep-wakefulness Paraventricular Magnocellular hormones (oxytocin, ); parvocellular; direct autonomic control Anterior Thirst Supraoptic Magnocellular hormones (oxytocin, vasopressin) Suprachiasmatic Circadian rhythm Ventromedial Appetitive/consummatory behaviors Dorsomedial Feeding, drinking, and body weight regulation Arcuate Parvocellular hormones; visceral functions Mammillary Memory Tuberomammillary Sleep-wakefulness (histamine) Lateral hypothalamic Various, including arousal, food intake; contain orexin SummarySummary ofof hypothalamushypothalamus functionsfunctions The 3rd Ventricle

 NNarrowarrow verticalvertical cleftcleft betweenbetween thethe twotwo halveshalves ofof thethe diencephalondiencephalon Lat. ventricle Fornix 3rd Ventricle  BordersBorders  thalamus  pl. choroideus  hypothalamus  lamina terminalis Lateral ventricle communicates with the 3 rd ventricle via the foramen of Monro

Four Parts: • Lateral Ventricle (2) • TheThe 33 rdrd ventricleventricle hashas 44 recessesrecesses

Foramen of  OOpticptic Monro  IInfundibularnfundibular  PPinealineal  SSuprapinealuprapineal Pineal recess RecessesRecesses ofof thethe 33 rdrd ventricleventricle

Suprapineal

Pineal

Optic Infundibular