Won Taek Lee, M.D., Ph.D. BasalGangliaBasalGanglia

Traditional Concepts of Basal Ganglia Traditional Concepts of Basal Ganglia Corpus Striatum Caudate Nucleus Caudate Nucleus Lenticular Nucleus Putamen Lenticular Nucleus Putamen Globus Pallidus Paleostriatum Pallidum Globus Pallidus Paleostriatum Pallidum Corpus Amygdaloideum Archistriatum Neostriatum Striatum Basal Ganglia Introduction Basal Ganglia Introduction

1. Putamen 2. Tail of caudate nucleus 3. Caudatolenticular gray bridge 4. Amygdaloid body 5. thalamus Lateral surface of basal ganglia

1. head of caudate nucelus caudate nucelus 2. body of caudate nucelus caudate nucelus 3. caudatolenticular gray bridge gray bridge 4. putamen 5. tail of caudate nucleus caudate nucleus 6. external segment of globus pallidus 7. internal segment of globus pallidus 8. amygdaloid body 9. nucleus accumbens septi Medial surface of basal ganglia

Components of Basal Ganglia Components of Basal Ganglia Corpus Striatum Striatum Caudate Nucleus & Putamen Striatum Caudate Nucleus & Putamen Pallidum Globus Pallidus (GP) Pallidum Globus Pallidus (GP) Substantia Nigra Pars Compacta (SNc) Pars Compacta (SNc) Pars Reticulata (SNr) Pars Reticulata (SNr) Subthalamic Nucleus (STN) Ventral Striatum and Ventral Pallidum Nucleus Accumbens Septi Nucleus Accumbens Septi Non cholinergic portion of Substantia Innominata Non cholinergic portion of Substantia Innominata Basal Ganglia Components Basal Ganglia Components

STRIATUM STRIATUM Caudate Nucleus Head, (Corpus), Tail Head, (Corpus), Tail caudatolenticular gray bridge caudatolenticular gray bridgePutamen Ventral Striatum: Nucleus Accumbens (Septi) Basal Ganglia Components Basal Ganglia Components

Striatal Compartments Striatal Compartments (Mosaic or Modular Organization) (Mosaic or Modular Organization) 1. Striosome (Patches) % of total striatal mass % of total striatal mass - low acetylcholinesterase (AchE) activity - low acetylcholinesterase (AchE) activity - high substance P (SP), neurotensin (NT), tyrosine hydroxylase - high substance P (SP), neurotensin (NT), tyrosine hydroxylase - high expression of D 1 dopamine receptor - high expression of D 1 dopamine receptor - high opiate receptor - high opiate receptor 2. Matrix - high acetylcholinesterase (AchE) activity - high acetylcholinesterase (AchE) activity - high somatostatin (SRIF) activity - high somatostatin (SRIF) activity - high D 2 dopamine receptor - high D 2 dopamine receptor Basal Ganglia Components Basal Ganglia Components

Spiny I neuron neuron Spiny II neuron neuron Aspiny I neuron neuron Aspiny II neuron neuron Aspiny III neuron neuronNeurogliform cell cell

Basal Ganglia Components Basal Ganglia Components Striosome and Matrix compartment AchE

Basal Ganglia Components Basal Ganglia Components Inputs to the spiny striatal neurons distal – extrinsic distal – extrinsic proximal - intrinsic proximal - intrinsic

PALLIDUM PALLIDUM Globus Pallidus (Pallidum) Internal or Medial Segment (GPi) Internal or Medial Segment (GPi) internal medullary lamina internal medullary lamina External or Lateral Segment (GPe) External or Lateral Segment (GPe) Ventral Pallidum Non-cholinergic portions Non-cholinergic portions of substantia innominata of substantia innominata Basal Ganglia Components

Substantia Nigra Substantia Nigra Pars Compacta (SNc) Dopaminergic Cell Group (A 9 ) Dopaminergic Cell Group (A 9 ) cf. Ventral Tegmental Area (VTA, A 10 ) cf. Ventral Tegmental Area (VTA, A 10 ) Retrorubral Area (A 8 ) Retrorubral Area (A 8 ) Pars Reticulata (SNr) Non-dopaminergic Portion Non-dopaminergic Portion GABAergic Neuron GABAergic Neuron Basal Ganglia Components

Subthalamus Subthalamus Subthalamic Nucleus (STN) zona incerta Field of Forel H ansa lenticularis H ansa lenticularis H1thalamic fasciculus H1thalamic fasciculus H2lenticular fasciculus H2lenticular fasciculus Basal Ganglia Components

Putamen Globus pallidus external segment external segment internal segment internal segment Subthalamic Nucleus Substantia nigra Internal capsule Components of Basal Ganglia

Basal Ganglia Components Subthalamic Nucleus 1. epithalamus 2. dorsal thalamus 3. subthalamus 3-1. subthalamic nucleus 3-2. zona incerta 3-3. globus pallidus 4. hypothalamus 5. putamen arrow: internal capsule Origin of subthalamic nucleus and putamen (Kuhlenbeck)

Input Portion Input Portion STRIATUM STRIATUM (Caudate Nucleus and Putamen) (Caudate Nucleus and Putamen) Output Portion Output Portion 1. PALLIDUM (Globus Pallidus) 1. PALLIDUM (Globus Pallidus) 2. SNr (Substantia Nigra, Pars Reticulata) 2. SNr (Substantia Nigra, Pars Reticulata) Basal Ganglia Connections

STRIATUM STRIATUM Afferents from 1. Cerebral Cortex [Corticostriatal Projection] 1. Cerebral Cortex [Corticostriatal Projection] 2. Thalamus (CM-PF complex) [Thalamostriatal Projection] 2. Thalamus (CM-PF complex) [Thalamostriatal Projection] 3. SNc (Substantia Nigra, pars compacta), 3. SNc (Substantia Nigra, pars compacta), Ventral Tegmental Area (VTA, A 10 ) Ventral Tegmental Area (VTA, A 10 ) and A 8 (Retrorubral Area) [Nigrostriatal Projection] and A 8 (Retrorubral Area) [Nigrostriatal Projection] 4. Dorsal Raphe Nucleus (B 6, B 8 ) [Raphestriatal Projection] 4. Dorsal Raphe Nucleus (B 6, B 8 ) [Raphestriatal Projection] 5. Amygdaloid Nuclear Complex [Amygdalostriatal Projection] 5. Amygdaloid Nuclear Complex [Amygdalostriatal Projection] Efferents to 1. Pallidum (GPi & GPe) [Striopallidal Projection] 1. Pallidum (GPi & GPe) [Striopallidal Projection] 2. SNr [Strionigral Projection] 2. SNr [Strionigral Projection] 3. SNc from striosome 3. SNc from striosome Basal Ganglia Connections

Afferent Connections of Basal Ganglia

Input-OutputRelationship of Basal Ganglia 1. striopallidal fiber 2. strionigral fiber 3. strionigral fiber from striosome from striosome to SNc to SNc 4. ventrostrio- ventro-pallidal fiber ventro-pallidal fiber

PALLIDUM (Globus Pallidus) PALLIDUM (Globus Pallidus) Afferents from 1. Striatum [Striatopallidal Projection] 2. STN [Subthalamopallidal Projection] Efferents to 1. Thalamus (VLo, VApc, CM) [Pallidothalamic Projection] 2. STN [Pallidosubthalamic Projection] SNr (Substantia Nigra, Pars Reticulata) SNr (Substantia Nigra, Pars Reticulata) Afferents from Striatum [Striatonigral Projection] Efferents to 1. Thalamus (VLm, VAmc, MD) [Nigrothalamic Projection] 2. Brain Stem Nucleus: Tectum (Superior Colliculus) & Pedunculopontine Nucleus (PPN) Pedunculopontine Nucleus (PPN) Basal Ganglia Connections

Efferent Connections of Basal Ganglia

Pallidothalamic Fibers Pallidothalamic Fibers from GPi to VLo, VApc, CM from GPi to VLo, VApc, CM Ansa Lenticularis from outer (lateral) portion of GPi from outer (lateral) portion of GPi fibers sweep ventromedially and rostrally around fibers sweep ventromedially and rostrally around the posterior limb of the internal capsule the posterior limb of the internal capsule enters Forel’s field H enters Forel’s field H Lenticular Fasciculus from inner (medial) portion of GPi from inner (medial) portion of GPi perforate internal capsule perforate internal capsule enters Forel’s field H 2 enters Forel’s field H 2 Thalamic fasciculus ansa lenticularis, lenticular fasciculus ansa lenticularis, lenticular fasciculus and cerebellothalamic fibers and cerebellothalamic fibers Forel’s field H 1 Forel’s field H 1 Basal Ganglia Connections

habenularnucleushabenularnucleus tectum (superior colliculus) tectum PPN (pedunculopontine nucleus) PPN amygdaloid body rapheraphe CerebralCortexCerebralCortex STNSTN PallidumSNrPallidumSNr STRIATUMSTRIATUM Connections of the Basal Ganglia SNcSNc ThalamusThalamus

Basal Ganglia (Main Motor Circuit) Connections Supplementary Motor Area (SMA) Primary (M I) THALAMUS (VLo, VApc, CM) STRIATUM(Putamen) PALLIDUM(GPi) pyramidal tract tract LMN ansa ansalenticularis lenticular lenticularfasciculus

Basal Ganglia (Prefronatal Complex Loop) Connections PrefrontalAssociationCortex Primary Motor Area (M I) THALAMUS (VLm, VAmc, MD) STRIATUM(CaudateNucleus) SNr (Substantia Nigra, pars reticulata) pyramidal tract tract LMN

GP, SNr StriatumMotorCortex VA-VLcomplex - GABA -GABA + glutamate ? glutamate + glutamate + Basal Ganglia (Microcircuitary) Connections

Basal Ganglia (Limbic Loop) Connections Orbitofrontal Cortex Anterior Cingulate Gyrus Hippocampal Formation THALAMUS (VAmc, MD) Ventral Striatum Caudate Nucleus Ventral Pallidum GPi, SNr

Basal Ganglia (Oculomotor Loop) Connections Frontal Eye Field (area 8) Primary Motor Area (M I) THALAMUS (VLm, VAmc, MD) STRIATUM(CaudateNucleus) SNr (Substantia Nigra, pars reticulata) pyramidal tract tract LMNTectum

Basal Ganglia (SNc and CM-PF nuclear complex) Connections Pallidum Striatum THALAMUS(CM-PF) Pallidum Striatum SNc

Basal Ganglia (Brain Stem Efferents) Phylogeny GPi SNr Tectum(superiorcolliculus) SpLnDCP DIP (thalamus) NeostriatumIntermediale (motor cortex) aves (birds) GPi SNr Tectum(superiorcolliculus) nPC VA-VL complex (thalamus) motorcortex mammals

Basal Ganglia (STN) Connections SNrGPi STN GPe subthalamic subthalamic fasciculus fasciculus OutputPortionofBasalGanglia Cerebral Coretx Thalamus (CM-PF) PPN SubthalamicNucleus

Basal Ganglia (Ventral Striatum and Ventral Pallidum) Connections VentralPallidumVentralStriatum HippocampalFormation BasolateralAmygdala Temporal & Frontal Cortex SNc, VTA & Dorsal Raphe Thalamus(MD) BasolateralAmygdala PPN & VTA Thalamus(MD)

Basal Ganglia (Brain Stem Efferents) Connections PPN(midbrain locomotor locomotor region) region) Tectum(superiorcolliculus) GPi, SNr Striatum (caudate nucleus) LowerMotorNeuron viareticularformation tectospinaltract Basal Ganglia Brain Stem & Spinal Cord

SMA (supplementary motor area) (supplementary motor area)SMA Basal Ganglia and Pyramidal Tract upper motor neuron upper motor neuron UMN UMN lower motor neuron lower motor neuron LMN LMN pyramidal tract tract BASAL BASALGANGLIA CIRCUIT CIRCUIT

Basal Forebrain Area Components BASAL FORBRAIN AREA (Heimer) Ventral Striatum, Part of Ventral Striatum, Part of Ventral Pallidum Ventral Pallidum Basal Nucleus of Meynert (Ch4) Basal Nucleus of Meynert (Ch4) Extended Amygdala Extended Amygdala cf. Cholinergic Cell Groups (Mesulam) cf. Cholinergic Cell Groups (Mesulam) (Magnocellular Basomedial Telencephalic Complex ) 1. Ch1 (Medial Septal Nucleus) 1. Ch1 (Medial Septal Nucleus) 2. Ch2 (Nucleus of Diagonal Band of Broca) 2. Ch2 (Nucleus of Diagonal Band of Broca) 3. Ch3 (Nucleus of Diagonal Band of Broca) 3. Ch3 (Nucleus of Diagonal Band of Broca) 4. Ch4 (Basal Nucleus of Meynert) 4. Ch4 (Basal Nucleus of Meynert) 5. Ch5 (Pedunculopontine Tegmental Nucleus) 5. Ch5 (Pedunculopontine Tegmental Nucleus)

Basal Ganglia Functional Consideration Functional Consideration Functional Consideration 1. Selection of “Preprogramed (learned) motor plans” Basal Gangla Circuit ---- Selection Mechanism Basal Gangla Circuit ---- Selection Mechanism Selection Inability Akinesia and Hypokinesia Selection Inability Akinesia and Hypokinesia Faulty Selection Hyperkinesia Faulty Selection Hyperkinesia 2. Generation (learning) of motor programs Programming of several motor fragments into Programming of several motor fragments into complex motor routines complex motor routines Cerebral Palsy Disordered motor program Cerebral Palsy Disordered motor program

SYDENHAM’S CHOREA - Complication of Rheumatic Fever Rheumatic Fever - Fine, disorganized, and random movements of random movements of extremities, face and extremities, face and tongue tongue - Accompanied by Muscular Hypotonia Muscular Hypotonia - Typical exaggeration of associated movements associated movements during voluntary activity during voluntary activity - Usually recovers spontaneously spontaneously in 1 to 4 months in 1 to 4 months Clinical Feature Principal Pathologic Lesion: Corpus Striatum

Clinical Feature Principal Pathologic Lesion: Corpus Striatum (esp. caudate nucleus) Corpus Striatum (esp. caudate nucleus) and Cerebral Cortex and Cerebral Cortex - Predominantly autosomal dominantly inherited chronic fatal disease inherited chronic fatal disease (Gene: chromosome 4) (Gene: chromosome 4) - Insidious onset: Usually Choreic movements in onset - Frequently associated with emotional disturbances emotional disturbances - Ultimately, grotesque gait and sever dysarthria, progressive dementia dysarthria, progressive dementia ensues. ensues. HUNTINGTON’S CHOREA

HEMIBALLISMHEMIBALLISM - Usually results from CVA (Cerebrovascular Accident) (Cerebrovascular Accident) involving subthalamic nucleus involving subthalamic nucleus - sudden onset - Violent, writhing, involuntary movements of wide excursion movements of wide excursion confined to one half of the body confined to one half of the body - The movements are continuous and often exhausting but cease and often exhausting but cease during sleep during sleep - Sometimes fatal due to exhaustion - Could be controlled by phenothiazines and stereotaxic phenothiazines and stereotaxic surgery surgery Clinical Feature Lesion: Subthalamic Nucleus

Muhammad Ali in Alanta Olympic Parkinson’s Disease Disease of mesostriatal dopaminergic system PD normal

Substantia Nigra, Substantia Nigra, Pars Compacta (SNc) Pars Compacta (SNc) DOPAminergic Neuron Slowness of Movement - Difficulty in Initiation and Cessation of Movement of Movement Clinical Feature (1) Parkinson’s Disease - Paralysis Agitans

Clinical Feature (2) Resting Tremor Parkinsonian Posture Rigidity-Cogwheel Rigidity Parkinson’s Disease Paralysis Agitans