Neuroanatomy Paper A PDF

        Neuroanatomy   Paper  A   Syllabic  content  3.1     © SPMM Course We...

        Neuroanatomy   Paper  A   Syllabic  content  3.1     © SPMM Course We claim copyright for our own text material, productions and adaptations. We claim no rights to Images/Figures with CC-BY-SA license if they are used in this material. ©  SPMM  Course   1   1. General anatomy of the brain A. Cortical structures The  cerebrum  has  four  major  lobes  (frontal,  temporal,  parietal  and  occipital  lobes).  The  lobar  surface  is   heavily  folded  forming  sulci  (valleys)  and  gyri  (ridges).  Primary  (major)  sulci  are  more  invariant  in  their   appearance  than  the  secondary  (minor)  sulci.     The  central  sulcus  divides  frontal  lobe  from  the  parietal  lobe.  Precentral  gyrus  (part  of  the  frontal  lobe)  is   the  primary  motor  cortex.  The  representation  of  different  body  parts  in  this  region  is  often  termed  as  a   homunculus.  Postcentral  gyrus  (part  of  the  parietal  lobe)  is  the  primary  somatosensory  cortex  with  a   similar  homunculus  representation.     The  lateral  sulcus  (Sylvian  fissure)  divides  frontal  lobe  from  the  temporal  lobe.  The  insula,  a  structure   that  is  sometimes  regarded  as  the  fifth  lobe  of  the  cerebrum,  is  located  deep  in  the  Sylvian  fissure.  Insula  is   the  seat  of  the  primary  gustatory  cortex.     Other  major  primary  sulci  include       1. Superior  and  inferior  frontal  sulci:  In  between  these  sulci  is  the  middle  frontal  gyrus  constituting   the  dorsolateral  prefrontal  cortex,  often  considered  to  be  responsible  for  executive  functions  of  the   human  brain.       2. Cingulate  sulcus  on  the  medial  side  of  the  frontal  lobe.  The  anterior  portion  of  the  adjoining   cingulate  gyrus  is  considered  to  be  the  seat  of  motivation.       3. Olfactory  and  orbital  sulci  on  the  inferior  surface  of  the  frontal  lobe.  The  orbitofrontal  cortex  is   often  considered  to  be  the  seat  of  associative  learning  and  decision-­‐‑making.     4. The  Superior  temporal  sulcus  is  forming  superior  temporal  gyrus,  the  seat  of  primary  auditory   cortex.     5. The  interparietal  sulcus  separates  superior  and  inferior  parietal  lobes.  The  inferior  parietal  lobe  is   made  of  the  angular  gyrus  and  supramarginal  gyrus  and  is  considered  to  be  important  for   visuospatial  attention.     6. Calcarine  sulcus  in  the  medial  occipital  cortex,  the  seat  of  primary  visual  (striate)  cortex     Hemispheric lateralisation ¬ Most  fundamental  brain  functions  are  represented  bilaterally.  Higher  levels  of  associative   functions  usually  lateralize  to  one  or  other  hemisphere.  For  example,  language  comprehension  is   localized  to  the  left  temporal  cortex  while  prosody  (tonal  modulation  of  speech)  seems  limited  to   the  right  hemisphere.   ¬ The  hemisphere  contralateral  to  the  dominant  hand  is  the  dominant  hemisphere,  and  it  mediates   language  and  speech  functions.     ¬ Dominance  can  be  tested  using  Annette’s  handedness  scale  or  Edinburgh  handedness  inventory.   But  handedness  is  not  always  same  as  dominance.   ©  SPMM  Course   2    ¬ In  right-­‐‑handed  people,  the  left  hemisphere  is  mostly  dominant.  In  10%  of  right-­‐‑handed  people,   the  right  hemisphere  is  dominant.  Among  left-­‐‑handed  people  only  about  20%  are  right   hemisphere  dominant,  with  64%  left  hemisphere  dominant  and  16%  showing  bilateral  dominance.   ¬ Size  asymmetry:  The  planum  temporale  is  a   Left  Hemisphere   Right  Hemisphere  lesions   triangular  region  on  the  upper  surface  of  the   lesions   superior  temporal  gyrus.  It  is  important  for   Aphasia   Visuospatial  deficits   language  processing  and  is  larger  on  the  left   Right-­‐‑left   Anosognosia   than  the  right  hemisphere  in  65%  brains.  It  is   disorientation   probably  the  most  asymmetrical  structure  in   Finger  agnosia   Neglect   the  human  brain,  with  some  individuals   Dysgraphia  (aphasic)   Dysgraphia  (spatial,  neglect)   Dyscalculia  (number   Dyscalculia  (spatial)   having  a  five  times  larger  planum  temporale   alexia)   on  the  left  than  on  the  right.  This  asymmetry   Limb  apraxia   Constructional  apraxia     is  reportedly  reduced  or  reversed  (right>left)   Dressing  apraxia     in  schizophrenia.     Face  recognition  (bilateral)     B. Subcortical structures Limbic system/ Papez circuit ¬ Broca  first  described  the  limbic  lobe.  Papez  and  later  Maclean  assigned  the  function  of  emotional   processing  to  limbic  structures  though  this  view  is  challenged  in  recent  times.     ¬ The  Papez  circuit  consists  of  the  hippocampus  →  fornix  →  mammillary  bodies  →   mammillothalamic  tract  →  anterior  thalamic  nucleus  →  genu  of  the  internal  capsule  →  cingulate   gyrus  →    parahippocampal  gyrus  →  entorhinal  cortex  →  perforant  pathway  →  back  to   hippocampus   ¬ The  boundaries  of  the  limbic  system  were  subsequently  expanded  outside  of  the  Papez  circuit  to   include  the  amygdala,  septum,  basal  forebrain,  nucleus  accumbens,  and  orbitofrontal  cortex.   ¬ The  limbic  system  is  thought  to  be  involved  in  various  functions  such  as  mediation  of  emotional   responses  (through  amygdala),  influencing  neuroendocrine  responses  (via  hypothalamus)  and   reward  system  regulation  (via  nucleus  accumbens).   ¬ The  limbic  system  is  often  considered  to  be  evolutionarily  older  than  the  higher  cortical  centres.     Medial temporal structures ¬ Include  the  hippocampus,  amygdala,  entorhinal  and  parahippocampal  cortex.     ¬ Hippocampus  appears  to  play  an  important  role  in  memory  processes.  It  is  one  of  the  few  brain   regions  where  the  continuous  production  of  new  neurons  is  noted  even  in  adult  life.   ¬ Amygdala  appears  crucial  for  fear  conditioning  and  emotional  regulation   Basal Ganglia ¬ The  basal  ganglia  are  a  group  of  gray  matter  nuclei  forming  the  largest  subcortical  structure  in  the   brain.  They  are  involved  in  the  planning  and  programming  of  movement,  and  also  have  a  role  in   the  processes  by  which  an  abstract  thought  is  converted  into  voluntary  action   ©  SPMM  Course   3    ¬ They  include  striatum  made  of  the  caudate  nucleus  and  putamen  and  pallidum  made  of  globus   pallidus.  Putamen  and  globus  pallidus  are  sometimes  called  lenticular/lentiform  nucleus.   ¬ The  subthalamic  nuclei  and  the  substantia  nigra  are  both  functionally  related  to  the  basal  ganglia   but  are  not  considered  to  be  a  part  of  this  structure.     ¬ Basal  ganglia  receive  crucial  inputs  from  glutamatergic  corticostriatal  projection.  Alexander   described  five  important  circuits  involving  the  basal  ganglia.  These  are   Motor  circuit   Oculomotor  circuit   Dorsolateral  prefrontal  circuit  (executive)   Anterior  cingulate  circuit  (motivation)   Lateral  orbitofrontal  circuit  (social  intelligence)     Disorder     Nature  of  basal  ganglia  dysfunction     OCD     Volumetric  changes  and  higher  blood  flow  to  the  caudate  nuclei.  Increased  caudate   metabolism  in  untreated  subjects  reduces  after  effective  treatment.     Tourette’s  syndrome   Striatal  dopaminergic  dysfunction   Huntington  chorea   Degeneration  of  the  striatum  (mainly  caudate  nucleus)  &  selective  loss  of  GABAergic   neurons   Wilson  disease   Copper  deposits  in  the  lenticular  nuclei     CO  poisoning   Acute  bilateral  anoxic  damage  to  basal  ganglia   Hemiballismus   Subthalamic  nucleus  damage  (especially  infarction)   Parkinsonism     Depigmentation  of  Substantia  Nigra;  Lewy  bodies  are  seen.  Striatal  overactivity   associated  with  bradykinesia   Fahr'ʹs  disease   Progressive  calcium  deposition  in  the  basal  ganglia.  (early  onset  cases  present  with   schizophreniform  psychoses  and  catatonia;  later  onset  cases  exhibit  dementia  and   choreoathetosis)   Thalamus ¬ A  large  oval  mass  of  grey  matter  nuclei  in  the  subcortical  region,  relaying  all  types  of  sensory   information  onto  cortex  (except  olfaction).   ¬ It  also  relays  cerebellar  and  basal  ganglia  inputs  to  the  cerebral  cortex.   ¬ The  thalamus  is  said  to  play  a  crucial  role  of  filtering  sensory  information  in  preparation  for   cortical  processing.   ¬ The  anterior  thalamus  is  a  part  of  the  limbic  system.  It  receives  the  mamillothalamic  tract  and   fornix  and  connects  to  the  cingulate  cortex.  Thus,  it  relays  information  from  hypothalamus  and   hippocampus  onto  the  frontal  cortex.   ¬ Pulvinar  is  associated  with  visual  attention.  Sleep  spindles  are  generated  in  the  reticular  nucleus  of   the  thalamus.   ©  SPMM  Course   4   Hypothalamus ¬ The  hypothalamus  regulates  physiological   INFERIOR  OLIVARY  NUCLEUS   functions  such  as  eating,  drinking,  sleeping,   and  temperature  regulation.   Inferior  olivary  nucleus  is  located  in  the   ¬ The  hypothalamus  has  chemoreceptors  that   brainstem  and  aids  in  motor  coordination  by   respond  to  variations  in  glucose  levels,   projecting  climbing  fibers  to  the  contralateral   cerebellar  cortex  via  inferior  cerebellar   osmolarity,  acid  balance,  etc.  It  also  plays  a   peduncle.   major  role  in  neuroendocrine  control.   Inferior  olivary  lesions  lead  to  appendicular   ¬ The  ventromedial  hypothalamus  acts  as  the  satiety   ataxia  due  to  motor  incoordination  of  the   centre  while  the  lateral  hypothalamus  is  the   contralateral  arm  and  leg.    Patients  with   feeding  centre.  In  animals  with  a  lesion  of   inferior  olivary  lesions  will  fail  the  finger-­‐‑nose   ventromedial  hypothalamus  hyperphagia  and   test,  mimicking  cerebellar  lesion.    But  unlike   obesity  are  noted.   cerebellar  lesions  that  result  in  ipsilateral  motor   incoordination,  the  contralateral  side  is  affected   C. Cerebellum in  olivary  lesions.   The  cerebellum  has  the  important  role  of  preparing  a   motor  plan  and  predicting  balance  needed  between   muscle  groups  to  carry  out  the  intended  action  smoothly.  Cerebellar  lesions  produce  ataxia  and  coarse   intentional  tremors,  along  with  hypotonia,  past  pointing  and  pendular  knee  jerk.       Increasingly  the  role  of  the  cerebellum  in  cognitive  processes  has  been  appreciated.  The  term  cognitive   dysmetria  (Andreasen)  refers  to  the  difficulty  in  coordinating  and  monitoring  the  process  of  receiving,   processing,  and  expressing  information  that  could  result  from  disrupted  cortico-­‐‑cerebellar  circuitry  in   schizophrenia.     D. Brain stem and cranial nerves The  brain  stem  is  made  of  the  midbrain,  pons  and  the  medulla.    Most  of  the  cranial  nerves  (9  out  of  12)   enter  or  exit  the  brain  from  the  brainstem.     The  midbrain  consists  of  superior  (conjugate  gaze  control)  and  inferior  colliculi  (auditory  source   localization).  The  substantia  nigra  is  also  located  in  the  midbrain  along  with  periaqueductal  grey  matter   that  plays  an  important  role  in  vocalization  and  freezing  response  to  threat  and  in  pain  suppression.     Pons  is  positioned  beneath  the  cerebellum  and  surrounds  the  upper  half  of  the  4th  ventricle   Medulla  surrounds  inferior  part  of  the  4th  ventricle  and  is  continuous  with  the  spinal  cord.     No. Name Anatomical features I Olfactory Runs on the basal surface of frontal cortex without passing through the thalamus. Formed as an outgrowth of forebrain II Optic Also an outgrowth of the forebrain. Relays via thalamus (geniculate body) III Oculomotor Purely motor function. Supplies four of the six ocular muscles IV Trochlear Purely motor function. Supplies superior oblique (ocular muscle) V Trigeminal Both sensory and motor. Transmits facial sensation and controls jaw muscles VI Abducens Purely motor function. Supplies lateral abducens (ocular muscle) ©  SPMM  Course   5    VII Facial Both sensory and motor. Transmits taste sensation and controls facial muscles VIII Vestibular Transmits auditory sensation Cochlear Transmits balance sensation IX Glossopharyngeal Motor control of pharynx; parasympathetic control of the parotid gland; taste from the back of the tongue. X Vagus Motor control of larynx and pharynx; parasympathetic control of the viscera; visceral sensations. XI Accessory Motor control of neck muscles XII Hypoglossal Motor control of tongue muscles   E. Spinal Cord Unlike  cerebrum  where  grey  matter  is  on  the  outer  surface,  in  spinal  cord  grey  matter  occupies  the  deeper   aspect  forming  an  H  shaped  column  surrounding  the  CSF.  The  white  matter  bundles  form  anterior,  lateral   and  dorsal  columns  around  the  grey  matter  zone.  The  dorsal  column  carries  proprioceptive  sensory  fibres;   the  anterior  and  lateral  columns  are  made  of  ascending  spinothalamic  tracts  carrying  touch,  pressure,   pain  and  temperature  sensations.     F. Cerebrospinal fluid CSF  is  secreted  by  the  choroid  plexus  in  the  lateral,  third  and  fourth  ventricles  and  at  a  rate  of  300  ml/day,   which  is  almost  protein  free.   Route:    From  lateral  ventricle  to  3rd  ventricle  via  interventricular  foramina  of  Monroe;  From  3rd  to  4th   ventricle  via  cerebral  aqueduct  of  Sylvius;  From  4th  ventricle  to  subarachnoid  space  via  foramen  of   Magendie  (single)  and  foramina  of  Luschka  (two  lateral).     The  body  of  the  lateral  ventricle  lies  immediately  below  the  corpus  callosum,  and  the  two  lateral  ventricles   are  separated  by  septum  pellucidum.  The  third  ventricle  lies  between  thalamus  and  hypothalamus.  The   fourth  ventricle  lies  above  the  pons  and  just  below  the  cerebellum.   Obstruction  to  CSF  circulation  commonly  occurs  within  third  or  fourth  ventricle  (foramen  of  Monroe),   leading  to  non-­‐‑communicating  hydrocephalus.  Impairment  of  CSF  reabsorption  in  the  subarachnoid   space  due  to  partial  occlusion  of  the  arachnoid  villi  leads  to  communicating  hydrocephalus.                   ©  SPMM  Course   6   2. Blood supply to the brain A. Major branches The  internal  carotid  artery  enters  the  circle  of  Willis  and  divides  to  form  the  anterior  cerebral  and  middle   cerebral  arteries.     The  anterior  cerebral  artery  supplies  the  medial  and  superior  strip  of  the  lateral  aspect  of  the  cerebral   cortex  up  to  the  parietal/occipital  border.   The  middle  cerebral  artery  supplies  most  of  the  lateral  aspect  of  the  cerebral  cortex.  This  includes  the   Broca’s  and  Wernicke’s  areas  in  the  dominant  hemispheres.     The  posterior  cerebral  artery  arises   from  basilar  artery  and  supplies  the   Carotid  system   Vertebrobasilar   inferomedial  temporal  lobe  and  the   TIA TIA occipital  lobe.   The  medulla  is  supplied  by  posterior   Amaurosis  fugax  (due  to   Diplopia,  vertigo,  vomiting blockade  of  retinal  arteries) Choking  and  dysarthria inferior  cerebellar  arteries  and  anterior   Aphasia Ataxia spinal  branches  of  vertebral  arteries.   Hemiparesis Alexia  without  agraphia Pons  is  supplied  by  the  basilar  artery   Hemisensory  loss Hemisensory  loss Hemianopic  visual  loss Hemianopic  visual  loss that  runs  along  the  midline  of  the  pons.   Transient  global  amnesia   Tetraparesis   Loss  of  consciousness  (rare) B. Effect of lesions   Artery   Supply   Lesion  effects   Anterior  Cerebral  Artery   Medial  surface  (ventromedial   Bilateral  infarct  produces  quadriparesis  (legs  weaker   (ACA)   frontal  lobe,  the  cingulum,  the   than  arms)  and  akinetic  mutism  (ventromedial  or   premotor  cortex,  and  medial   cingulate  syndrome)   motor  strip)   Recurrent  artery  of   Head  of  the  caudate  nucleus   Initially  an  agitated,  confused  state;  evolves  to   Huebner  (branch  of  ACA)   akinesia,  abulia,  with  mutism  and  personality  changes   Anterior  branches  of  the   Lateral  prefrontal  cortex   Planning  deficits,  impairment  of  working  memory,   upper  division  of  the   and  apathy.  (DLPFC  dysfunction)   Middle  Cerebral  Artery     Anterior  communicating   Basal  forebrain   Akinesia  and  personality  change  (orbitofrontal   artery   dysfunction)  with  a  confabulatory  amnesia   resembling  Wernicke-­‐‑Korsakoff  syndrome.   Posterior  inferior   Lateral  medulla   Wallenberg'ʹs  lateral  medullary  syndrome.  Acute   cerebellar  artery  (PICA)   vertigo  with  cerebellar  signs.  Ipsilateral  face   thrombosis   numbness,  diplopia,  nystagmus,  Horner’s  syndrome   and  IX/X  nerve  palsy  with  contralateral  spinothalamic   sensory  loss  and  mild  hemiparesis.     ©  SPMM  Course   7   3. White matter pathways There  are  3  major  types  of  white  matter  pathways.  Projection  fibers  run  vertically  connecting  higher  and   lower  centres  of  the  brain.        Association  fibers  interconnect  different  regions  within  the  same  hemisphere   of  the  brain.    Commissural  fibers  interconnect  similar  regions  in    the  opposite  hemisphere.     Corpus  callosum  is  the  largest  bundle  of  fibres  that  connect  the  two  cerebral  hemispheres;  the  other  such   bundles  are  anterior  commissure  (interconnects  olfactory  bulbs),  posterior  commissure  (interconnects   midbrain  pretectal  nuclei),  hippocampal  commissure  and  habenular  commissure  (interconnects  posterior   dorsal  thalamic  nuclei).     The  pericallosal  artery  derived  from  the  anterior  cerebral  artery  provides  blood  supply  to  the  anterior   aspect  and  most  of  the  body  of  the  corpus  callosum.  Left  sided  apraxia  and  agnosia  may  be  seen  in  cases   of  vascular  disruption.     Posterior  cerebral  artery  territory  supplies  splenium  (posterior  aspect  of  the  corpus  callosum)  and   disrupted  supply  here  prevents  right  visual  cortex  accessing  the  dominant  hemispheric  processes  such  as   language  resulting  in  alexia  and  color  anomia  but  with  preserved  ability  to  copy  words  as  motor   information  is  relayed  via  anterior  corpus  callosum     Fornix  is  an  important  white  mater  tract  that  connects  hippocampus  to  the  hypothalamus  via  mammillary   bodies.  Thus,  it  relays  cortical  input  to  regulate  neuroendocrine  and  autonomic  systems.     Arcuate  fasciculus  connects  Broca’s  and  Wernicke’s  areas.  Damage  results  in  conduction  aphasia.     Uncinate  fasciculus  is  a  major  frontotemporal  tract  that  connects  orbitofrontal  cortex  to  the  anterior   temporal  lobes.  It  plays  an  important  role  in  social  cognition  and  language.                         ©  SPMM  Course   8   4. Cell types in the nervous system A. Cortical layers The  human  brain  contains  approximately  1011  neurons  (nerve  cells)  and  approximately  1012  glial  cells.   According  to  the  distribution  of  the  various  types  of  neurons  (i.e.  the  cytoarchitecture),  Brodmann  divided   the  cortex  into  47  ‘specialised’  areas.       The  neocortex  (most  of  the  cerebrum)  is  made  up  of  six  layers,  with  pial  surface  above  layer  1  to  the  white   matter  below  layer  6.    Layers  2  and  4  are  mainly  afferent  (receiving  inputs)  while  5  and  6  are  mainly   efferent  (sending  outputs).   The  pyramidal  neurons  with  their  triangular-­‐‑shaped  cell  bodies  make  up  nearly  75%  of  the  cortical   neurons.  Stellate  cells  (25%)  are  present  in  all  the  layers  except  layer  1.     Layer   Name   Predominant  cells   1   Molecular/agranular   Glial  cells,  dendrites  from  neurons  of  deeper  layers  and  the   horizontal  cells  of  Cajal.   2   External  Granular  layer   Granule  cells  and  small  pyramidal  cells  (these  get  larger  as  you   move  down)   3   External  Pyramidal  layer     Small  and  medium  sized  pyramidal  cells.   4   Internal  Granular  layer   Some  pyramidal  cells,  mostly  granule  cells.  Receives     thalamocortical  inputs.     5   Internal  Pyramidal  layer   Largest  pyramidal  cells  (esp.  in  motor  cortex:  Betz  cells)   6   Multiform  layer   A  mixture  of  all  cells,  spindle  cells,  Martinotti  cells.  The  major   source  of  corticothalamic  fibres.  Gives  rise  to   association/commissural  and  projection  fibres.       The  cerebellar  cortex  is  three  layered.    The  molecular  layer  consisting  of  basket  cells  and  stellate  cells,   Purkinje  layer  consisting  of  Purkinje  cells  and  a  Granular  layer  consisting  of  granule  and  Golgi  cells.   B. Special neuronal cell types Purkinje  cells  are  a  class  of  GABAergic  neurons  located  in  the  cerebellar  cortex  only.  Purkinje  cells  form     the  sole  output  of  all  motor  coordination  in  the  cerebellum  they  connect  to  the  deep  cerebellar  nuclei  via     inhibitory  projections.     Granule  cells  are  found  within  the  granular  layer  of  the  cerebellum,  layer  4  of  the  cerebral  cortex,  the   dentate  gyrus  of  the  hippocampus,  and  in  the  olfactory  bulb.     Large  pyramidal  cells  called  Betz  cells  are  seen  in  the  primary  motor  cortex.  Betz  cells  are  pyramidal  cell   neurons  located  within  the  fifth  layer  of  the  grey  matter  in  the  primary  motor  cortex.  These  neurons  are   ©  SPMM  Course   9   the  largest  in  the  central  nervous  system,  sometimes  reaching  100  µμm  in  diameter.  Betz  cells  represent   about  10%  of  the  total  pyramidal  cell  population  in  layer  V  of  the  human  primary  motor  cortex.   Stellate  cells  are  found  in  layer  IV  of  the  cerebral  cortex  (from  thalamus  feeding  forward  to  pyramidal   cells)  and  also  in  the  cerebellum.     C. Glial cells BLOOD  BRAIN  BARRIER   These  are  cells  with  supportive  metabolic  functions;     they  also  participate  in  modulating  neuronal   The  blood-­‐‑  brain  barrier  is  located  in  endothelial  cells   functions  e.g.  via  the  production  of  neurosteroids.   of  capillaries  of  the  brain.  Unlike  the  endothelial  cells   There  are  3  types  of  glial  cells:   found  elsewhere,  brain’s  endothelial  cells  have  tight   junctions  with  high  electrical  resistance  providing  an   1. Astrocytes  are  the  most  numerous  of  the   effective  barrier  against  molecules.    In  addition,  brain   three  types.  These  are  star-­‐‑shaped  cells  that   capillaries  are  in  contact  with  foot  processes  of   enable  nutrition  of  neurons,  breakdown  of   astrocytes  that  separate  the  capillaries  from  the   some  neurotransmitters,  and  maintaining  the   neurons.     blood-­‐‑brain  barrier.     Lipid  soluble  molecules  (ethanol  and  caffeine)  can   2. Oligodendrocytes  are  seen  in  CNS  (not  in   penetrate  the  barrier  relatively  easily  via  the  lipid   peripheral  nerves,  where  Schwann  cells   membranes  of  the  cells.  In  contrast,  water-­‐‑soluble   replace  them).  They  produce  myelin  sheaths   molecules  such  as  sodium  and  potassium  ions  are  unable   that  help  in  saltatory  conduction  (pole  to  pole   to  transverse  the  barrier  without  using  specialized   jumping),  which  quicken  the  process  of  signal   carrier-­‐‑mediated  transport  mechanisms.   transmission.       Inflammation  such  as  meningitis  weakens  the  blood   3. The  microglia  are  descendants  of   brain  barrier.   macrophages.  They  are  scavenger  cells  that     clear  neuronal  debris  following  cell  death.   There  are  some  areas  of  the  brain  that  do  not  have  a   4. Ependymal  cells  are  a  special  type  of  glia  that   blood-­‐‑  brain  barrier.  These  are  so  called  circum-­‐‑ cover  the  ventricles  and  facilitate  CSF   ventricular  organs  e.g.  subfornical  organ,  area   circulation  via  their  ciliary  processes.   postrema  (chemo  receptor  trigger  zone),  median   eminence  and  posterior  pituitary.                   ©  SPMM  Course   10   5. Major neurochemical pathways A. Dopaminergic pathways Depending  on  the  length  of  the  projections,  dopaminergic  pathways  can  be  classified  into   1. Long  paths:  Nigrostriatal,  mesocortical  and  mesolimbic  pathways.     2. Short  paths:  Tuberoinfundibular  and  incertohypothalamic  pathway.     3. Ultrashort  paths:  These  are  found  in  the  amacrine  cells  in  the  retina  and  in  the  olfactory  system.   The  nigrostriatal  pathway  is  the  extrapyramidal  pathway  that  is  crucial  for  motor  control;  this  accounts  for   most  of  the  brain’s  dopamine.       Pathway   Origin  and  destination   Effect  of  dopamine  (DA)  blockade   Nigrostriatal   Substantia  Nigra  to  striatum  and   DA  deficiency  (e.g  Parkinson’s)  or  blockade  due   amygdala  via  medial  forebrain  bundle   to  antipsychotics  can  cause  extrapyramidal  side   effects     Mesolimbic   Ventral  tegmental  area  (VTA)  to   Blockade  of  DA  in  this  tract  produces  the   Nucleus  accumbens  and  hippocampus   desirable  antipsychotic  effect  by  controlling   via  medial  forebrain  bundle   positive  psychotic  symptoms   Mesocortical   Ventral  tegmental  area  (VTA)  to   Low  levels  of  DA  or  DA  blockade  in  this  tract  is   cingulate  cortex  and  prefrontal  regions     associated  with  negative  symptoms  (alogia,   via  medial  forebrain  bundle   anhedonia,  amotivation  and  apathy)   Tuberoinfundibular   Hypothalamus  to  the  pituitary  via   Dopamine  acts  as  PIH  –  prolactin  inhibitory   portal  vessels     hormone.  DA  blockade  will  serve  to  increase     prolactin  levels.   Incertohypothalamic   Internal  connections  within   Disturbed  thermoregulation  and  possibly   hypothalamus   weight  gain       B. Cholinergic pathways The  two  major  cholinergic  pathways  are   1. Brainstem  pathway:  This  forms  a  part  of  the  ARAS    -­‐‑  ascending  reticular  activating  system  that  is   important  to  maintain  wakefulness  and  REM  sleep  state.    It  originates  from  pedunculopontine   and  laterodorsal  tegmental  nuclei  and  innervates  thalamic  relay  neurons  and  reticular  nuclei.     2. Basal  forebrain  pathway:  Originates  at  the  Nucleus  Basalis  of  Meynert  in  basal  forebrain  and   projects  to  the  hippocampus,  frontal  cortex  and  amygdala.  Degeneration  of  this  pathway  is   implicated  in  Alzheimer'ʹs  disease.     ©  SPMM  Course   11    C. Serotonergic pathways Most  of  the  brain’s  serotonergic  neurons  originate  in  the  midbrain  dorsal  and  median  raphe  nuclei  and   ascend  to  innervate  the  entire  cortex,  basal  ganglia,  thalamus,  and  also  descend  to  the  spinal  cord.   D. Noradrenergic pathways Noradrenergic  projection  originates  at  the  locus  coeruleus  (pons)  and  ascends  to  most  of  the  cortex  via   medial  forebrain  bundle.  Similar  to  the  serotonin  system,  noradrenergic  projections  also  descend  to  the   spinal  cord.       E. Glutamatergic system Glutamate  is  the  most  common  excitatory  neurotransmitter  in  the  brain.  As  a  result,  almost  all  cortical   descending  tracts  (from  pyramidal  cells)  rely  on  glutamate  for  neurotransmission.  This  large  output  of   corticofugal  fibres  makes  up  most  of  the  corona  radiata.  All  of  the  association  and  commissural  fibres   also  use  glutamatergic  transmission.  Many  thalamic  neurons  are  also  glutamatergic.  Thus  thalamocortical   projections  are  also  glutamatergic.  In  addition  cerebellar  output  from  deep  nuclei,  subthalamic  nuclei  to   globus  pallidus  projections,  and  brainstem  to  spinal  cord  projections  are  also  predominantly   glutamatergic.   F. GABAergic system GABA  is  the  primary  inhibitory  neurotransmitter  in  the  brain.    Unlike  other  neurotransmitters,  there  are   no  specific  neurochemical  pathways  where  GABA  is  dominant.  Instead,  GABA  is  the  major  transmitter  for   cerebral  interneurons  that  are  ubiquitous  throughout  the  cortex.   Interneurons  are  usually  short  neurons  that  serve  to  connect  two  other  neurons,  thus  forming  an  essential   part  of  the  complex  wiring  pattern  of  the  cortex.  They  carry  neither  motor  nor  sensory  information  but   serve  to  modulate  local  neural  circuitry.     2  major  cortical  interneuron  subtypes  are  noted:  parvalbumin  (PV)-­‐‑expressing  interneurons  (~40%  of  all   interneurons)  and  somatostatin  (SST)-­‐‑expressing  interneurons  (30%  of  interneurons,  also  called   Martinotti  cells).     A  reduction  in  the  expression  of  PV-­‐‑interneurons  in  the  frontal  cortex  is  now  a  well-­‐‑replicated  feature  of   schizophrenia.  PV-­‐‑interneurons  are  of  2  subtypes:  Basket  cells  and  Chandelier  cells.   Basket  cells  receive  direct  input  from  thalamocortical  projections.  They  form  synapses  with  the  soma  or   dendrites  of  the  pyramidal  neurons  and  serve  to  provide  the  excitatory-­‐‑inhibitory  balance  to  the  cortex.   Chandelier  cells  form  synapses  with  the  proximal  axonal  hillock  of  pyramidal  neurons.  They  may  have   an  overall  excitatory  role  by  serving  to  short-­‐‑circuit  the  action  potential  propagation  though  their  role  is   still  unclear.       ©  SPMM  Course   12                DISCLAIMER: This material is developed from various revision notes assembled while preparing for MRCPsych exams. The content is periodically updated with excerpts from various published sources including peer-reviewed journals, websites, patient information leaflets and books. These sources are cited and acknowledged wherever possible; due to the structure of this material, acknowledgements have not been possible for every passage/fact that is common knowledge in psychiatry. We do not check the accuracy of drug related information using external sources; no part of these notes should be used as prescribing information.   Notes prepared using excerpts from: ! Heide  et  al.  Dissecting  the  uncinate  fasciculus:  disorders,  controversies  and  a  hypothesis.  Brain.   2013  Jun;136(Pt  6):1692-­‐‑707.     ! Ruigrok  TJ.  Cerebellar  nuclei:  the  olivary  connection.  Prog  Brain  Res.  1997;114:167-­‐‑92.   ! Lewis  DA  et  al.  Cortical  parvalbumin  interneurons  and  cognitive  dysfunction  in  schizophrenia.   Trends  in  Neurosciences  2012  Jan;35(1):57-­‐‑67.     ! Andreasen  NC  et  al.  "ʺCognitive  dysmetria"ʺ  as  an  integrative  theory  of  schizophrenia:  a   dysfunction  in  cortical-­‐‑subcortical-­‐‑cerebellar  circuitry?  Schizophr  Bull.  1998;24(2):203-­‐‑18.   ©  SPMM  Course   13