Anat 6.5 Basal Ganglia_Quijano (1)

Anatomy  6.5    

 

Feb  14,  2012   Dr.  Quijano  

Basal Ganglia System

  OUTLINE   I.  Motor  Control   II.  Basal  Ganglia  System   A.  Components   B.  Nomenclature   III.  Connections  of  Basal  Ganglia   IV.  Basal  Ganglia  Feedback  Loops   V.  Basal  Ganglia  Diseases   A.  Parkinson’s  Disease   B.  Chorea  

Figure   1.Motor   control   system.   Alpha   motor   neurons   are   the   final   common  path  for  motor  control.  Peripheral  sensory  input  and  spinal  cord   tract   signals   that   descend   from   the   brainstem   and   cerebral   cortex   influence  the  motor  neurons.  The  cerebellum  and  basal  ganglia  contribute   to  motor  control  by  modifying  brainstem  and  cortical  activity.    

Objectives:   • Name  the  3  systems  involved  in  the  suprasegmental  mechanism  of   voluntary  motor  control.     • Describe  the  basal  ganglia    and  its  composition       • Enumerate  the  sources  of  the  afferent  fibers  to  the  basal  ganglia.         • State  the  parts  of  the  basal  ganglia  where  almost  all  the  afferent  impulses   terminate  and  where  almost  all  afferent  fibers  arise.     • Name  the  efferent  tracts  from  the  globuspallidus   • Trace  the  different  circuitry  within  the  basal  ganglia  and  name  the   neurotransmitters  involved.     • Describe  the  common  basal  ganglia  disorders    

I.MOTOR  CONTROL   • Evolution  of  Movement.  Movement  is  a  fundamental  and   essential  property  of  animal  life.     o In  simple,  unicellular  animals,  motion  depends  on  the   contractility  of  protoplasm  and  the  action  of  accessory  organs:   cilia,  flagella,  etc   o Rudimentary  multicellular  animals  possess  primitive   neuromuscular  mechanisms   o In  more  advanced  forms  of  animal  life,  reflexive  motion  is   based  on  the  transmission  of  impulses  from  the  receptor   through  the  afferent  neuron  and  ganglion  cell  to  motor   neurons  &  muscles  =  which  is  found  in  the  REFLEX  ARC.      Reflex  arc  is  seen  in  higher  form  of  animals  with  developed   Spinal  Cord.  Superimposed  on  these  reflex  circuits,  the  Brain   is  concerned  with  the  initiation  and  control  of  movement  and   the  integration  of  complex  motions.     • Motor  system  in  humans  control  complex  neuromuscular   network.  Commands  must  be  sent  to  many  muscles,  and  many   joints  must  be  stabilized.    

• Muscular  actvity  by  reflexes  (eg.  knee  jerk  reflex)  is  controlled  at   the  spinal  level.     • Stereotypic   repetitious   movement   (eg.   walking)   is   controlled   by   spinal  cord,  brainstem  and  cerebellum   • Specific,   goal   directed   movement   (fine   motor   movement   like   buttoning  your  shirt)  is  initiated  by  cerebral  cortex.       • There  are  3  Systems  in  Suprasegmental  Control   1. Pyramidal  System   o Direct  control  over  the  motor  neurons   2. Basal  ganglia  –  inhibitory  output   o Indirect  control  over  motor  neurons  (influences  motor  cortex,   which  in  turn,  brings  down  the  effect  to  the  motor  neuron   3. Cerebellum  –  excitatory  output   o Also  indirect  control    Basal  Ganglia  &  Cerebellum  modify  movement  on  a  minute-­‐to-­‐ minute  basis.      Cortical  Modulation  is  thru  recurrent  circuits.       • There  are  2  Circuits  of  Motor  System   o Pyramidal   System   –   the   primary   control   of   voluntary   movement  thru  (1)  corticospinal  or  the  pyramidal  tract  and  (2)   corticotubular  pathways   o Extrapyramidal   System   (EPS)   –   (1)   Basal   Ganglia   is   clinically   the   EPS  and  (2)  Cerebellum  

 

 

Figure  2.  Motor  control  and  its  modulation    

  Group  2  |  Agulto,  Agustin  B,  Al-­‐qaseer,  Alano,  Alastra,  Alegre,  Almario  

 

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II.  BASAL  GANGLIA  SYSTEM:  Overview   • Basal  Ganglia  are  a  collection  of  subcortical  nuclei  of   telencephalon,  subthalamus  &  midbrain  that  modulate  motor  and   cognitive  functions  of  motor  complex.  (Gilman  &  Newman)   • The  term  is  applied  to  a  collection  of  masses  of  gray  matter   situated  within  each  cerebral  hemisphere  which  includes  the  (1)   corpus  striatum,  (2)  amygdaloid  nucleus,  and  (3)  the  claustrum.   th (Snell,  7 ed)   • Movements  influenced  by  the  basal  ganglia  include  those  related   to:     o Posture   o Automatic  movements  (eg.  swinging  of  arms  while  walking)   o Skilled  volitional  movements  of  the  trunk  and  limbs   o It  also  participates  in  cognition.       A.  Components  of  the  Basal  Ganglia   • Telencephalic  Nuclei   o Caudate  (Tail)   o Putamen  (shell)   o Globus  pallidus  (pale)   o Nucleus  accumbens  (leaning)    HISTORICALY,  the  claustrum  and  amygdale     • Nontelencephalic  Nuclei   o Subthalamic  nucleus   o Substantianigra  

 

Figure  3.  The  components  of  the  basal  ganglia.  

  B.  Nomenclature  of  the  Basal  Ganglia  

Figure  4.  Organization  of  basal  ganglia  

 

• The  term  STRIATUM  is  used  to  describe  the  Caudate  Nucleus   PLUS  the  Putamen.     • Corpus  Striatum  is  striatum  PLUS  Lentiform  Nucleus.     o “striped  body”   o lateral  to  the  thalamus  and  divided  by  sheets  of  myelinated   fibers  and  internal  capsule  into:    Caudate  nucleus  (tail)  –  C-­‐shaped  mass  of  gray  matter.  This  is   the  largest  nucleus.     o It  lies  dorsolateral  to  the  thalamus  and  is  closely  related  to   the  parts  of  the  lateral  ventricles.     o It  has  a  head,  body  and  tail   • Head o largest part and continuous and bulges at the cephalic end o continuous inferiorly with the putamen of the lentiform nucleus o caudate nucleus + putamen = neostriatum or striatum o forms the lateral wall of the anterior horn of the lateral ventricle • Body o Continuous with the head in the region of the interventricular foramen o forms part of the floor of the body of the lateral ventricle • Tail o Continuous with the body in the region of the posterior end of the thalamus o Terminates anteriorly in the amygdaloid nucleus o Follows the contour of the lateral ventricle and continues forward in the roof of the inferior horn of the lateral ventricle • Internal  capsule  is  a  small  but  crucial  band  of  projection  fibers   that  separate  the  lentiform  nucleus  from  the  medial  caudate   nucleus  and  the  thalamus.     o Recall  –  3  types  of  fibers:  (1)  commissural  fibers,  (2)  association   fibers,  and  (3)  projection  fibers   • Commisural fibers o Connect corresponding regions of the two hemispheres (corpus callosum, posterior commisure, fornix, and habenular commissure) • Association fibers o Connect various cortical regions within the same hemisphere and maybe divided into short and long groups o Short association fibers – lie immediately beneath the cortex and connect adjacent gyri; run transversely to the long axis of the sulci o Long association fibers – collected into named bundles that can be dissected in a formalin-hardened brain • Projection fibers o Afferent and efferent nerve fibers passing to and from the brainstem to the entire cerebral cortex must travel between large nuclear masses of gray matter within the cerebral hemisphere o At the upper part of the brainstem, these fibers form a compact band known as the internal capsule o Afferent  &  efferent  nerve  fibers  passing  to  and  from  the   brainstem  to  the  entire  cerebral  cortex  must  travel  between   large  nuclear  masses  of  gray  matter  within  the  cerebral   hemisphere.  At  the  upper  part  of  the  brainstem,  these  fibers   form  a  compact  band  –  the  Internal  Capsule.     o It  is  flanked  medially  by  the  caudate  nucleus  and  the  thalamus.     o Because  of  the  wedge-­‐shaped  lenticular  nucleus,  the  internal   capsule  is  bent  to  form  the  anterior  limb  and  a  posterior  limb   on  horizontal  section.    

Group  2  |  Agustin  B,  Al-­‐Qaseer,  Alegre,  Almario,  Almazan,  Almodiente,  Altabano,  Alvarez

 

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• Lentiform  Nucleus   o Thumb-sized mass of gray matter wedged against the internal capsule o Wedge-shaped mass of gray matter whose broad convex base is directed laterally and its blade medially o Buried deep in the white matter of the cerebral hemisphere and o Related medially to the internal capsule which separates it from the caudate nucleus and the thalamus o Related laterally to a thin sheet of white matter, the external capsule which separates it from a thin sheet of gray matter called the the claustrum o Divided into putamen and globus pallidus  Putamen • Larger and darker lateral portion • Has the same histological appearance as the caudate nucleus, with numerous and densely packed small neurons • Contains granules with Ach that account for its darker color  Globus Pallidus • Lighter medial region • Contains sparsely distributed large cells and traversed by many myelinated fibers • Paleness due to the high concentrations of myelinated fibers • A cell sparse lamina separates the globus pallidus itself into: external globus pallidus and internal globus pallidus NOTES:   • Almost all efferents from GB arise from GPi (w/c contain the inhibitory neurotransmitter, GABA • GPi sends (1) Major inhibitory output from BG back to thalamus and (2) few projections to area of midbrain to assist in postural control • Both GPe and GPi receive info from caudate and putamen • They both are in communication with subthalamic nucleus • They also provide output to substantia nigra • Posterior limb of internal capsule: separates lentiform nucleus from thalamus • anterior limb of the internal capsule: separates lentiform from head of caudate nucleus.

  • Striatum  (aka  Neostriatum,  Dorsal  Striatum)  =  Putamen  +  Caudate   o Acetylcholine  is  the  neurotransmitter  of  interneurons   o An  acetylcholinesterase  (AChE)  stains  for  the  enzyme  that   degrades  acetylcholine  (ACh).     o It  receives  major  inputs  to  the  basal  ganglia  provided  by   afferents  from  the  cerebral  cortex,  thalamus  and  substantia   nigra.   o Receives  excitatory  input  from  neurons  in  all  areas  of  the   isocortex,  causing  excitation  w  ith  GABA  as  the  neurotrans   mitter   o Stimulation  of  cerebral  cortical  neurons  evoke  sequences  of   excitatory(fromglutamatergiccorticalefferents),followedby   inhibitory  postsynaptic  potentials  (from  GABA-­‐ergic   interneurons  in  striatum)   o Projections  have  a  topographic  organization  that  is  continued   by  neurons  that  project  from  the  substantia  nigra  pars   reticulate  and  to  the  internal  and  external  globus  pallidus   o Neurons  from  the  striatum  to  the  external  pallidum  provide   inhibition  using  GABA  and  encephalin   o Neurons  from  striatum  to  the  internal  pallidum  also  inhibit   using  GABA  and  Substance  P     Projection   Areas   Putamen   Areas  4,  6  (lateral  and  medial)  and  3,1,2   Caudate  nucleus   Frontal  eye  fields  and  association  areas  of  the   frontal  and  parietal  lobes  

  • Amygdaloid  Nucleus   o Situated in the temporal close to the uncus o Considered part of the limbic system o Influences the body’s response to environmental changes     • Claustrum   o Thin sheet of gray matter that is separated from the lateral surface of the lentiform nucleus by the external capsule o Lateral to the claustrum is the subcortical white matter of the insula o Function is still unknown

Figure  5.  Striatum  (putamen  and  capsule)  

 

  NON-­‐TELENCEPHALIC  NUCLEUS:   • Subthalamic  Nuclei   o part  of  diencephalon   o largest  nuclear  mass  in  the  subthalamus   o Shape  of  a  biconvex  lens  between  thalamus  &  tegmentum,  just   rostral  to  midbrain   o Has important connections with corpus striatum; as a result needed for the integration of smooth movements of different parts of the body o Disorders:  Ballism/Hemiballism   o Main  mass  of  midbrain  between  cerebral  peduncles  and   cerebral  aqueducts   o Functionally  closely  related  to  the  activities  of  the  basal  nuclei   o Neurons  are  glutaminergic  and  excitatory   o Have  many  connections  to  the  globus  pallidus  and  substantia   nigra   • Substantia  Nigra   o Non-­‐telencephalic  nucleus  =  lies  in  upper  midbrain;  between   the  cerebral  peduncle  &  tegmentum   o The nucleus is composed of medium-size multipolar neurons that possess inclusion granules of melanin pigment within their cytoplasm o In  a  brain  specimen,  SN  neurons  appear  brownish-­‐black  due  to   neuromelanin   o The  SN  neurons  are  dopaminergic  and  inhibitory  (  +  ;  -­‐  )   o It is concerned with muscle tone and is connected to the cerebral cortex, spinal cord, hypothalamus, and basal nuclei o Neuromelanin gives its color: “black substance” o Have many connections to the corpus striatum o It has 2 superior and 2 inferior colliculi o 2  parts  of  the  Substantia  Nigra  

Group  2  |  Agustin  B,  Al-­‐Qaseer,  Alegre,  Almario,  Almazan,  Almodiente,  Altabano,  Alvarez

 

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 Substancia  Nigra  pars  compacta  (SNc)  –    this  is  the  part  that   degenerates  in  Parkinson’s  disease.  It  is  treated  by  giving  oral   dopamine  precursors.   o Receives  input  from  striatum  and  sends  it  back  to  striatum   or  sends  it  to  the  outside  of  the  basal  ganglia  to  control   head  and  eye  movement    SubstanciaNIgra  pars  reticulata  (SNr)  –  porjects  to  superior   colliculi  and  uses  GABA  as  a  neurotransmitter     III.    CONNECTIONS  OF  BASAL  GANGLIA   Generalization  (REMEMBER!)   ALMOST  ALL  of  the  input  or  afferent  fibers  are  received  by  the   STRIATUM.  The  GLOBUS  PALLIDUS  (mainly  the  interna,  or  medial   part)  forms  the  major  site  from  which  the  output  or  efferent  fibers   leave  the  basal  nuclei.     • Afferent  fibers  TO  the  striatum  or  basal  ganglia:   1.  Cerebral  cortex  –  the  corticostriate  fibers    Preferentially:  From  the  cerebral  cortex  to  the  putamen    Only  some  fibers  (from  Area  8)  will  go  to  caudate  nucleus    Primary  Motor  cortex  (MI)  =  Area  4    Supplementary  Motor  Cortex  (MII)  =  Area  6    Pre  Motor  Area  =  Area  6    Somotosensory  cortices  =  Area  3,1,2    Uses  Glutamate  as  its  neurotransmitter  (strongly  excitatory)    

 

Figure  7.  Some  of  the  major  connections  between  the  cerebral  cortex,  the   basal  nuclei,  the  thalamic  nuclei,  the  brainstem,  and  the  spinal  cord.  

    Figure  8.  Basal  nuclei  pathways  showing  the  known  neurotransmitters.      

Figure  6.  Schematic  diagram  of  prinicipal  connections  of  basal  ganglia.      

2.  Thalamus  (only  from  intralaminar  nuclei/centromedian)  –   thalamostriate  fibers   3.  Substantia  nigra  –  nigrostriate  fibers  using  dopamine  as  its   neurotransmitter.  Overall  effect  is  inhibitory.  Involved  in   Parkinson’s  disease.   4.  Brainstem  striatal  fibers  using  serotonin.  Inhibitory.  

 

• Efferent  fibers  FROM  the  Striatum:   1. Striatopallidal  fibers    GPE  =  strong  inhibitory  input    GPI   2. Stiratonigral  fibers  –  inhibitory     • Efferent  fibers  FROM  the  Globus  Pallidus  =  Pallidofugal  fibers   1. Fasciculus  Lenticularis  –  to  subthalamus  (across  posterior  limb   of  internal  capsule)   2. Ansa  Lenticularis  –  to  thalamic  nuclei  (loop  around  the  ventral   aspect  of  posterior  limb  of  internal  capsule;  ansa=”loop”)   3. Pallidosubthalamic  fibers  –  to  subthalamic  nucleus  (STN)   4. Pallidotegmental  fibers  –  to  caudal  tegmentum  (from  ansa   lenticularis,  it  could  go  down  to  tegmentum  and  form  the   pallidotegmental  fibers)    Fasciculus  lenticularis  +  Ansalenticularis  =  Thalamic  fasciculus  

   ALMOST  all  impulses  terminate  in  the  Striatum  are  excitatory    Interneurons  within  the  striatum  are  excitatory  and  use  Ach.    

Group  2  |  Agustin  B,  Al-­‐Qaseer,  Alegre,  Almario,  Almazan,  Almodiente,  Altabano,  Alvarez

 

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(e.g.  striatum  inhibits  GPI/SNr  which  is  an  inhibitor  of  thalamus,  so   thalamus  will  be  released  from  the  inhibiting  effect  of  GPI/SNr)    

• Basal  Ganglia  efferent  fibers  TO  the  brainstem:   o Superior  colliculus  –  regulation  of  saccadic  eye  movements   o Pedunculopontinetegemental  neuron  (PPTN)  –  coordinates   status  of  arousal  with  fundamental  motor  patterns  (REM)  

Figure  9.  Principal  physiologic  circuitry  and  neurotransmitters  in  the  basal   ganglia.  

 

  IV.  BASAL  GANGLIA  FEEDBACK  LOOPS   1. Cortico  +  striato  –  pallido  –  thalamo  +  cortical  pathway     o It  is  the  long  loop   o From  cortex  to  striatum,  and  thalamus  to  cortex,  it  is  excitatory   o From  striatum  to  globus  pallidus,  and  pallidus  to  thalamus,  it  is   inhibitory   2. Direct  loop  (nigrostriatal  fibers)   o Cortico  +  striato  –  pallido/snr  –  thalamo  +  cortical  pathway   o D1  receptors  on  striatum  are  stimulated,  which  are  excitatory   o Cortex→  striatum→  SNr-­‐SNc→  striatum(D1)→  G  pallidus→   thalamus→  back  to  cortex  

Figure  10.  Direct  and  indirect  Loop   Black  arrows  represents  excitatory  effect,  red  arrows  represents  inhibitory   effect.   REMEMBER:     • excitatory  stimulus  to  an  inhibitor,  will  increase  its  ability  to  inhibit  (e.g.   cortex  to  striatum)   • inhibitory  stimulus  to  an  inhibitor,  will  decrease  its  ability  to  inhibit,  thus   releasing/exicitng/stimulating  the  succeeding  nuclei  

 

3. Indirect  loop  (nigrostriatal  fibers)  –  the  subthalamic  nucleus   influence  the  outflow  of  the  globus  pallidus  interna.     o Cortico  +  striato  –  pallido  ext  –  stn  +  pallido  int/snr  –  thalamo   –  cortical  pathway   o D2  receptors  are  stimulated,  which  are  inhibitory   o Cortex→  striatum→  SNr-­‐SNc→  striatum(D2)  →  G   pallidus(ext.)→    subthalamic  nucleus→  G  pallidus  (int.)→   thalamus→  cortex   o The  striatal  efferent  fibers  reach  the  external  segment  of  the   GP  and  after  synspases,  pallidal  efferent  fibers  cross  the   posterior  limb  of  the  internal  capsule  to  reach  the  subthalamic   nucleus  (STN).     o Neurons  of  the  STN  project  excitatory  glutamatergic  fibers  back   to  both  GP,  but  primarily  to  the  internal  segment,  and  to  the   substantia  nigra  reticulate  (SNr)  where  they  excite  GABAergic   projections  to  the  thalamus  and  thereby  inhibit  it.     o The  STN  also  receive  direct  input  from  the  cerebral  cortex.     Memory  trick  for  Neurotransmitters:     • All  excitatory  stimulus  uses  glutamate   • All  inhibitory  stimulus  uses  GABA   • EXCEPT  for  Dopamine  from  SNCompacta   o Dopamine  in  INdirect  loop  (D2)  is  Inhibitory  (IN-­‐IN)   o Dopamine  in  direct  loop  (D1)  is  excitatory   OVERALL  basal  ganglia  effect:  INHIBITORY   The  Basal  ganglia  function  is  described  as  the  “brake  hypothesis.”     Ex:  To  sit  still,  put  the  brakes  on  and  all  movements  except  those   reflexes  that  maintain  an  upright  posture.  To  move,  apply  a  brake  to   some  postural  reflexes  and  release  brake  on  voluntary  movement.     The  disturbances  could  lead  to:   1.  Presence  of  extraneous  unwanted  movements   2.  Absence  or  difficulty  with  intended  movements     V.  BASAL  GANGLIA  DISEASES   • The  are  three  functional  categories  (Manter&Gatz):   o Parkinsonism  –  degeneration  of  the  substantia  nigra   o Hyperkinetic  movement  (Ballism,  chorea,  athetosis)  –  from   striatal  or  subthalamic  dysfunction   o Dystonia  –  from  pallidal  dysfunction     • Two  General  Types  (Snell):   o Hypokinetic  disorders  –  lack  or  slowness  of  movement   o Hyperkinetic  movemnt  –  excessive  and  abnormal  movements   (ballism,  chorea,  athetosis)    Parkinson’s  disease  includes  both  types     A.  Parkinson’s  Disease   • Results  from  slow  and  steady  loss  of  dopaminergic  neurons  in   SNc.     • Aka  Paralysis  Agitans   • Concerned  with  lesions  on  the  basal  ganglia   • Symptoms  usually  include  the  ff:   o Tremors  when  at  rest  (pin-­‐rolling  movement)   o Rigidity  due  to  simultaneous  contraction  of  flexors  and   extensors  (cogwheel  rigidity)   o Bradykinesia  or  slow  movement   st o Festinating  gait  –  difficulty  initiating  1  steps,  but  once  under   way,  pace  becomes  more  rapid  (short,  shuffling  steps)  and  has   trouble  stopping  

Group  2  |  Agustin  B,  Al-­‐Qaseer,  Alegre,  Almario,  Almazan,  Almodiente,  Altabano,  Alvarez

 

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o Postural  disturbances  –  stooped  posture  with  loss  of  arm  swing   when  walking   o Masked  face  –  expressionless   o Depression  and  anxiety  problems  with  memory  loss  and   dementia   o No  loss  of  muscle  power  nor  sensiblities   • Parkinson’s  usually  develop  late  in  life.     • REMEMBER:  Parkinson’s  disease  involves  the  nigrostriatal   dopaminergic  pathway  

Figure  11.  Section  of  the  brain  affected  by  Parkinson’s  disease  

 Basal  ganglia  affects  final  common  path  or  LMN  INDIRECTLY    Basal  ganglia  effects  are  contralateral  to  the  side  of  the  lesion    Strength  persists  in  muscles  but  there  is  emergence  of  involuntary   movement.  

 

  B.  Chorea   • A  form  of  striatal  disorder   • Exhibits  involuntary,  quick,  jerky,  irregular  nonrepetitive   movements.  Ex:  swift  grimaces  and  sudden  movements  of  limbs   and  head.     • May  affect  limbs  (refers  more  to  distal  movements),  face,  tongue     • Huntington’s  disease  –  hereditary,  defect  on  chromosome  4   (protein  huntingtin).     o Degeneration  of  neurons  of  caudate  nucleus   o Disease  is  characterized  by  chorea  and  progressive  dementia     • Sydenham’s  Chorea  aka  St.  Vitus  Dance   o Disease  of  childhood   o Associated  with  rheumatic  fever  (streptococcal  antigens  have   same  membrane  proteins  of  striatal  neurons)   o Choreic  movements   o Disease  is  transient  and  with  full  recovery     • Athetosis   o Characterized  by  slow  writhing  worm-­‐like  involuntary   movement  of  extremities,  trunk,  and  neck   o Involves  the  cerebral  cortex  and  the  basal  ganglia   o Ex:  TICS,  Tourette’ssyndrom   o Aka  choreoathetosis     • Dystonia   o Fixed  posture  or  sustained  postural  contraction  of  limb,  neck   and  facial  muscles   o Most  commonly  secondary  to  cerebral  palsy     • Ballism  or  Hemiballismus   o Involuntary  flailing  movements  of  arm/s  and  leg/s   o Caused  by  damage  (i.e.  stroke)  of  opposite  subthalamic   nucleus.       Group  2  |  Agustin  B,  Al-­‐Qaseer,  Alegre,  Almario,  Almazan,  Almodiente,  Altabano,  Alvarez

 

Figure   12.   A.   Conceptual   model   of   activity   in   the   basal   ganglia   and   associated   and   associated   thalamocortical   regions   under   normal   circumstances.   Dark   arrows   indicate   inhibitory   connections,   and   open   arrows   indicate   excitatory   connections.   B.   Changes   in   activity   in   Parkinson’s   disease.   As   a   result   of   degeneration   of   the   pars   compacta   of   the   substantia   nigra,   differential   changes   occur   in   the   two   striatopallidal   projections   (as   indicated   by   altered   thickness   of   the   arrows),   including   increased  output  from  GPi  to  the  thalamus.  D,  direct  pathway;  I,  indirect   pathway;  GPe,  external  segment  of  globus  pallidus;  GPi,  internal  segment   of   globus   pallidus;   SNr,   substantia   nigra   (pars   reticulate);   SNc,   subsantia   nigra   (pars   compacta);   STN,   subthalamic   nucleus;   VL,   ventrolateral   thalamus.    

 

 

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