Paper  A(2)  Basic  Neurosciences  

Neuroanatomy  &  Neurochemistry  
 
 
I.  Neuroanatomy  ...............................................................................................................  2  
General  Neuroanatomy:  ................................................................................................  2  
1.1   Microanatomy  ........................................................................................................  2  
1.2   Functional  Neuroanatomy:  ....................................................................................  3  
1.3   Specific  Deficits  associated  with  focal  lesions:  ....................................................  6  
1.4   Functions  of  the  major  Gyri:  .................................................................................  9  
1.5   Diencephalic  structures  ........................................................................................  9  
1.6   White  matter  pathways  .........................................................................................  11  
1.7   Cranial  nerves:  ......................................................................................................  12  
1.8   The  Blood  supply  of  the  brain  .............................................................................  16  
II.   Neurochemistry  ........................................................................................................  18  
2.1   Monoamine  Neurotransmitters:  .........................................................................  19  
2.2   Dopamine:  .............................................................................................................  19  
2.3   Noradrenaline:  ......................................................................................................  21  
2.4   Serotonin:  ..............................................................................................................  21  
2.5   Histamine  ..............................................................................................................  23  
2.6   Acetylcholine:  .......................................................................................................  23  
2.7   Amino  acid  neurotransmitters:  ..........................................................................  24  
 
Paper A2: Neuroanatomy & Neurochemistry

I.  Neuroanatomy  

General  Neuroanatomy:  
The   human   nervous   system   can   be   divided   into   two   basic   parts:   the   central   nervous  
system,  which  consists  of  the  brain  and  spinal  cord,  and  the  peripheral  nervous  system,  
which   consists   of   cranial   and   spinal   nerves   and   other   neuronal   processes   and   cell  
bodies  lying  outside  the  central  nervous  system.  
The  cerebral  cortex  is  the  outermost  layer  of  grey  matter  of  the  cerebral  hemispheres.  
The   brain   stem   consists   of   the   medulla   oblongata,   pons   and   mesencephalon.   The  
cerebellum  consists  of  two  lateral  cerebellar  hemispheres  and  a  median  vermis.  
1.1   Microanatomy  
Cells   in   the   CNS   can   be   divided   into   two   general   types—neurons   and   neuroglia.  
Neurons  constitute  the  basic  unit  for  neural  communication  and  are  the  primary  target  
of   psychotropic   agents.   Neuroglia   are   considered   primarily   supportive   (e.g.,   provide  
regulatory   and   metabolic   functions   and   structural   support)   but   also   have   an  
increasingly   recognized   role   in   modulating   neural   communication.   Some   estimates  
suggest  that  brain  volume  is  somewhat  evenly  divided  between  neurons  and  neuroglia,  
although  neuroglia  out  number  neurons  in  some  brain  areas  by  10:1.  
Neurones:    
Neurones  are  the  cells  in  the  nervous  system  which  are  responsible  for  sending  
messages.  They  have  three  major  purposes:  
§ to  gather  and  send  information  from  the  senses  such  as  touch,  smell,  sight  etc.    
§ to  send  appropriate  signals  to  effector  cells  such  as  muscles,  glands  etc.    
§ to  process  all  information  gathered  and  provide  a  memory  and  cognitive  
ability  thus  allowing  us  to  take  voluntary  action  on  information  received.    
 
Neurones  are  divided  into  different  regions  each  having  a  different  function  and  are  
characterised  as  having:    
§ a  cell  body  containing  the  nucleus  and  most  of  the  organelles  responsible  for  
maintaining  the  cell.    
§ a  long  process  or  axon  stretching  out  of  the  cell,  sometimes  over  a  very  long  
distance  which  is  responsible  for  transmitting  signals  from  the  neurone  to  
other  cells.    
§ several  short  processes  called  dendrites  which  increase  the  surface  area  
available  for  connecting  with  axons  of  other  neurones.    
§ specialised  cell  junctions  called  synapses  between  its  axon  and  other  cells  
which  allow  for  direct  communication  from  one  cell  to  another.  
 
Neurones   are   classified   into   unipolar,   bipolar   and   multipolar   depending   on   the  
number  of  neurites.  Neurones  are  also  classified  into  2  types  based  on  the  size.  Golgi  
type  I  neurones  have  long  axon  and  type  II  have  short  axon.  
 

2
Paper A2: Neuroanatomy & Neurochemistry

Neuroglia:      
The   interstitial   cells   make   up   most   of   the   nervous   tissue   (5-­‐   10   times   more   than   the  
neurones).   The   4   types   of   neuroglia   in   the   CNS   are   astrocytes,   oligodendrocytes,  
microglia   and   ependyma.   The   2   types   of   neuroglia   in   the   PNS   are   Schwann   cells   and  
satellite  cells.  
Unlike  neurons,  neuroglia  continues  to  divide  and  multiple  throughout  the  life  of  the  
organism.   Traditionally   glial   cells   were   thought   to   provide   mainly   a   supportive  
function  (e.g.,  structural  support),  but  there  is  now  evidence  that  they  also  participate  
in   metabolic   processes   and   provide   important   regulatory   functions   for   neuronal  
activity   (e.g.,   absorb   excess   K+).   Because   of   their   ability   to   multiply,   the   role   of   glial  
cells   in   response   to   injury   has   long   been   recognized.   This   same   ability   to   multiply   may  
also   give   glial   cells   a   role   in   long-­‐term   neuroadaptive   effects   (e.g.,   pharmacological  
tolerance).  Functions  of  the  Neuroglia  include  the  below.  
§ Astrocytes  
  Metabolic  functions    
  Phagocytosis    
  structural  support,  including  help  in  forming  the  Blood  brain  barrier.  
§ Microglia  
  Phagocytosis  (especially  in  response  to  cell  injury)    
§ Oligodendrocytes  (CNS  only)  
  Formation  &  maintenance  of  myelin  sheath    
structural  support    
Nutrition  of  neurons  
§ Schawnn  Cells  (PNS  only)  
  Formation  and  maintenance  myelin  sheath    
Structural  support    
§ Ependymal  cells  
  Circulation  of  CSF.  
 
1.2   Functional  Neuroanatomy:  
 
Hemisphere  specialisation  
Left   hemisphere   (dominant)   specialised   for:   comprehension/expression   of   language,  
arithmetic,  and  analytic  functions.  Language  is  localised  to  left  hemisphere  in  99%  of  
right-­‐handed  people  and  2/3  of  left-­‐handed  people.    
Right   hemisphere   (non-­‐dominant)   specialised   for:   Complex   non-­‐verbal   perceptual  
tasks,  prosody  of  speech,  visual  and  spatial  perception,  expression  and  mediation  of  all  
aspects  of  emotionality.  
Lobe  functions:  
The   frontal   lobe   conducts   three   functions:   motor   activity   and   integration   of   muscle  
activity,  speech,  social  and  motivated  behaviour.    
The  parietal  lobe  is  associated  with  the  sensory  cortex  and  processes  information  about  
touch,  taste,  pressure,  pain,  and  heat  and  cold.    

3
Paper A2: Neuroanatomy & Neurochemistry

The  occipital  lobe  receives  and  processes  visual  information.    

The   temporal   lobe   is   associated   with   perception   and   recognition   of   auditory   stimuli,  
memory,  and  speech  

   
 
Figure:  Lobes  and  their  functions1.  
Lobe  dysfunctions:  
a.   Features  of  frontal  lobe  dysfunction:  
Non-­‐dominant   Dominant   Other/  General  Deficits  
Deficits  in  expression   Broca’s  area,  Exner’s     ‘Executive  Functions’  deficits  
of  emotional  /   writing  area,  Frontal   ‘Theory  of  Mind’  deficits  
melodic  speech   Eye  Fields:  reduces   Orbital  lesions:    
Tangentiality  in   motor  responsiveness   - Apathy  -­‐  if  the  damage  is  severe;  
speech,  verbosity,  and   and  behavioural   emotional  disinhibition  if  
in  extreme-­‐   expression     damage  is  mild    
confabulation     - Deficits  in  shifting  of  attention    
  - Perseveration  of  verbal  and  
motor  responses  
Frontal  Lobe  personality:  2  distinct  
types  depending  on  site  of  lesion  
Orbital  frontal:  Disinhibition,  
impulsivity,  hyperactivity  with  a  
tendency  to  confabulate  
Medial  Frontal:  Apathy,  
hypoactivity,  confusion,  lethargy  
and  depression  
Neurological  deficits:  
§ Expressive  dysphasia  
§ Contralateral  hemiplegia  
§ Bowel  bladder  dysfunction.  
§ Ipsilateral  Optic  atrophy  
§ Anosomia  

                                                                                                                         
1  [Link]  

4
Paper A2: Neuroanatomy & Neurochemistry

Three   specific   syndromes   are   described   –   usually   secondary   to   vascular   or   tumour  

related  pathology.  
1.   Orbitofrontal   syndrome   (pseudopsychopathic)   patients   are   disinhibited,   making  
tactless  remarks  and  acting  on  impulse.  They  lack  empathy,  and  show  little  concern  for  
the   feelings   of   others.   They   fail   to   plan   ahead   and   exhibit   little   concern   about   their  
illness   or   future.   Mood   is   typically   irritable   and   labile   with   a   fatuous   euphoria.  
Inappropriate   jocularity   with   an   insensitive   humor   (witzelsucht)   may   be   observed.  
There  is  a  lack  of  social  restraint  and  an  undue  familiarity  with  strangers.  But  they  have  
few   or   no   neuropsychological   deficits   and   exhibit   intact   language,   memory,   and  
visuospatial  skills.  Deficits  in  olfaction  commonly  accompany  the  syndrome  because  of  
the  proximity  of  the  olfactory  nerves,  bulbs,  and  tracts  to  the  orbital  surface.    
2.  Medial  frontal  lobe  syndrome  (pseudodepressive)  extends  from  akinetic  mutism  
at   the   most   severe   end   of   the   spectrum   to   a   mild   lack   of   motivation   on   the   other.  
Akinetic   mutism   occurs   with   bilateral   medial   frontal   lesions   and   is   characterized   by  
mutism  and  very  limited  spontaneous  movement.  The  patients,  however,  appear  alert,  
have   their   eyes   open,   exhibit   ocular   following   movements   of   environmental   events,  
will  eat  when  fed,  and  may  move  with  persistent  stimulation  or  pain.  Loss  of  initiative,  
poor   motivation,   limited   gesturing,   and   apathy   characterise   the   spontaneous  
behaviour  of  patients  with  medial  frontal  lesions.  
3.   Dorsolateral   prefrontal   syndrome   (dysexecutive)   produce   abnormalities   of  
sequential   behaviour   including   perseveration   (abnormal   continuation   of   behaviour),  
impersistence   (abnormal   early   termination   of   behaviour),   deficits   in   set   shifting,   and  
disturbances   of   programming   sequential   motor   acts   such   as   alternating   programs.  
Patients  exhibit  poor  judgment,  and  are  concrete  on  tests  of  abstraction.    
b.   Temporal  lobe  lesions:      
Non-­‐dominant   Dominant   Other/  General  Deficits  
Amusia   Receptive  aphasias   Homonymous  upper  
Amnesic  syndromes   Amnesic  syndromes   quadrantiopia  
(non-­‐verbal)   (verbal)   Auditory-­‐verbal  hallucinations  
Visual  Agnosias.   Neocortical  deafness  
Memory  deficits  (medial  
temporal)  
Personality  changes  like  
increased  religiosity  due  to  TLE  
Plays   a   major   part   in   producing   psychotic   symptoms   in   schizophrenia   especially  
hallucinations.  Role  of  medial  temporal/hippocampal  elements  in  depression  is  under  
scrutiny.  
c.   Parietal  lobe  lesions:  
Non-­‐dominant   Dominant   Other/  General  Deficits  
Topograhical   Inferior  Parietal:   Tactile  Recognition  
disorientation   Gerstmann’s   Attentional  impairments  and  

5
Paper A2: Neuroanatomy & Neurochemistry

Agnosias  – syndrome-­‐  finger   neglect  (more  common  in  right  

visuospatial   agnosia,  acalculia,   lesions)  
Constructionl  apraxia   agraphia,  left-­‐right   Anosognosia:  denial  of  hemiparesis  
Prosopagnosia   disorientation   Homonymous  lower  quadrantiopia,  
Language  deficits   asterognosis,  reduced  
(agraphia)   discrimination.  
 
Parietal   lobe   lesions   per   se   are   not   frequently   associated   with   psychiatric   symptoms.  
Tumors   of   the   parietal   lobe   can   produce   contralateral   sensory   loss,   particularly  
involving   joint   position   sense,   two-­‐point   discrimination,   astereognosis,   and  
agraphesthesia  (so  called  cortical  sensations).    
Lesions  in  the  dominant  parietal  lobe  are  associated  with  aphasia,  while  lesions  in  the  
nondominant  parietal  lobe  may  result  in  neglect  of  the  contralateral  side  and  the  loss  
of  ability  to  acknowledge  deficits  (anosonognosia).  Parietal  lobe  lesions  may  also  lead  
to   hemiparesis,   homonymous   visual   deficits   (or   neglect),   agnosia,   apraxias,   sensory  
seizures,  and  disturbance  of  visual  spatial  ability.    
Parietal   lesions  of  dominant   lobe   causes  Gerstmann   syndrome   (see   above).  The   non  
dominant   lobe   is   important   for   maintaining   body   image   –   delusions   of   control   are  
implicated   to   have   parietal   psychopathology.   Astereognosis   is   loss   of   ability   to   infer  
the   qualities   of   an   object   by   touch   without   seeing   (e.g.   coin   given   to   blind-­‐folded  
person).   It   is   tested   on   each   side   individually   and   so   both   lobes   play   part.  
Agraphaesthesia  refers  to  inability  to  infer  what  is  written  or  drawn  on  skin  without  
looking   at   it.   Bilateral   lesions   cause   Balint’s   syndrome   (see   below).   Parietal   lobe  
being  superiorly  located  to  temporal  lobe,  includes  upper  portion  of  optic  radiation  –  
lesions   cause   inferior   quadrantonopia.   Note   that   temporal   lesions   cause   superior  
quadrantonopia.  
1.3   Specific  Deficits  associated  with  focal  lesions:  
1.   Aphasia  
 
Type       Fluency         Comprehension       Repetition    
Wernicke's     Fluent       Impaired     Impaired    
Conduction     Fluent       Normal     Impaired    
Broca's       NonFluent     Normal     Impaired  
 
In   all   these   aphasias,   reading   aloud,   writing   and   naming   are   impaired   but   reading  
comprehension  is  preserved  in  Broca’s  and  Conduction.  
Aphasia:   Impairment   of   language   function,   inability   either   to   speak   (motor   aphasia)  
or   to   comprehend   (sensory   receptive   aphasia),   due   to   cortical   lesion   in   the   left  
hemisphere.  
Broca’s   aphasia   (primary   motor,   non-­‐fluent   or   expressive   aphasia)   is   characterised   by  
decreased   and   laboured   speech   output.   Small   grammatical   words   and   the   endings   of  
nouns  are  omitted  leading  to  telegraphic  speech.  The  patient  will  not  be  able  to  repeat  

6
Paper A2: Neuroanatomy & Neurochemistry

what   has   been   said   to   them.   Auditory   comprehension   is   preserved.   Most   commonly  
due  to  stroke  affecting  the  middle  cerebral  artery  regions.  
Wernicke’s   Aphasia   (fluent,   primary   sensory   or   receptive)   is   characterised   by   low  
normal   to   supernormal   output.   Auditory   comprehension   and   fluency   are   intact   but  
repetition  is  impaired.  Speech  is  produced  with  little  or  no  effort;  pauses  to  search  for  
words   are   frequent.   Substitution   without   language   (Paraphasia)   is   common   –  
substitution  of  a  syllable  (literal:  wellow  for  yellow);  Phonemic  substitution  of  a  word  
(verbal  -­‐  kench  for  wrench);  semantic  substitution  (knife  for  a  fork)  or  a  substitution  of  
a  meaningless  nonsense  word  (neologisms).  
In  aphasia  in  bilingual  patients,  the  language  in  which  there  is  greatest  loss  may  vary  
and   can   change   over   time.     However,   there   is   a   tendency   for   more   recovery   of   the  
primary  or  dominant  language.  
2.   Dyscalculia  is  generally  associated  with  left  parietal  lesion  (Gerstmann).  Other  
components  of  Gerstmann  syndrome  are  right-­‐left  disorientation,  alexia  with  agraphia  
and  finger  agnosia.  Dyscalculia  can  be  due  to  frontal  lesions  especially  resulting  from  
loss   of   abstract   mathematical   concepts   and   temporal   lesions   secondary   to   loss   of  
memory  of  stored  arithmetic  facts.  
3.   Prosopagnosia  results  from  lesions  in  the  occipital  and  non-­‐dominant  parietal  
lobes.  In  prosopagnosia  there  is  an  impaired  recognition  of  familiar  faces  -­‐  though  the  
patient  can  differentiate  facial  features,  she  cannot  recognize  familiar  individuals  such  
as   friends,   family   and   celebrities.   Patient   will   recognize   familiar   individuals   by   their  
voices.  Prosopagnosia  can  occur  with  lesions  limited  to  the  right  posterior  hemisphere,  
though   most   have   bilateral   posterior   hemispheric   injuries.  
4.   Unilateral   neglect   refers   to   a   hemi-­‐inattention   disorder   in   which   the   patient  
fails   to   attend   to   or   act   on   stimuli   in   one   half   of   the   field.   Visual   neglect   is   most  
common   but   hemi-­‐sensory   neglect   can   include   all   sensory   modalities   (e.g.,   hearing,  
touch).  Hemi-­‐motor  neglect  may  also  occur,  with  the  patient  failing  to  act  in  one  half  
side.  Hemi-­‐sensory  neglect  is  more  common  with  lesions  of  the  right  parietal  lobe  than  
with   left-­‐sided   lesions,   but   it   occurs   with   injury   to   either   hemisphere.   In   Right  
posterior  parietal  lesion,  the  ability  to  understand  the  significance  of  sensory  stimuli  is  
impaired   resulting   in   contralateral   sensory   neglect   and   inattention.   Sensory  
inattention   is   operationally   defined   as   failure   to   report   one   of   two   simultaneously  
presented   sensory   stimuli,   despite   the   fact   that   either   stimulus   alone   is   correctly  
reported.  Motor  neglect  occurs  with  frontal  or  subcortical  damage.  
5.   Anosognosia   refers   to   the   denial   of   hemiparesis   that   occurs   in   some   patients  
with  unilateral  neglect.  The  term  has  been  extended  to  encompass  all  forms  of  denial  
of  illness.  Hemisomatognosia  refers  to  neglect  of  one  side  of  the  body  when  there  is  
no   hemiparesis,   and   somatophrenia   is   the   term   for   denial   of   ownership   of   one's  
paretic   limbs.   When   limb   weakness   is   acknowledged   but   minimized   (no   emotional  
accompaniment),   the   term   anosodiaphoria   is   used;   hatred   of   a   weak   limb   is   called  
misoplegia.   Personification   (e.g.,   naming   the   limb,   etc)   is   another   form   of  
anosognosia.  
6.   Apraxia:  Apraxia  is  defined  as  the  inability  to  carry  out  a  motor  act  despite  the  
absence   of   sensory   or   motor   deficits.   So   the   tome   will   be   normal   and   patient   can  
understand   the   command.   There   are   many   classifications   of   apraxia   according   to  

7
Paper A2: Neuroanatomy & Neurochemistry

region   affected   –   e.g.   oculomotor,   orofacial,   limb   etc   or   according   to   specific  

component   found   defective.   With   the   exception   of   dressing   and   constructional  
apraxia,   apraxic   abnormalities   are   usually   secondary   to   left   hemisphere   damage,   in  
particular,  injuries  involving  the  left  frontal  and  inferior  parietal  lobes  
§ Ideomotor  apraxia  refers  to  failure  to  complete  an  act  on  command  but  retained  
ability   to   do   on   ones’   own.   They   are   abnormalities   of   learned   motor   behavior   that  
occur  in  the  absence  of  motor,  sensory,  or  comprehension  deficits.    
§ Patients  with  ideational  apraxia  cannot  perform  a  series  of  acts  although  they  may  
be   able   to   perform   the   individual   components   of   the   series.   For   example,   making  
coffee   requires   filling   the   coffee   maker   with   coffee,   adding   water   then   turning   on  
the  coffee  maker.  Patients  with  ideational  apraxia  may  correctly  perform  each  step  
but  place  them  out  of  order,  such  as  turning  on  the  coffee  maker  first.  There  is  no  
localising  value  for  this  and  it  is  seen  in  variety  of  dementias.  
§ Conceptual   apraxia   might   result   in   using   the   wrong   object   to   perform   a  
movement,  such  as  attempting  to  use  a  toothbrush  to  eat.  
§ Dressing   apraxia   or   construction   apraxia   is   seen   more   in   right   hemisphere  
damages  –  evident  when  the  patient  is  asked  to  wear  a  shirt,  he  might  use  it  turned  
inside-­‐out  or  upside  down.  It  is  thought  to  be  related  to  general  disturbance  in  body  
image  orientation  that  is  seen  in  right  parietal  damage.  
§ Orofacial  or  buccolingual  apraxia  is  noted  when  asking  to  low  a  candle  –  patient  
cannot  mimic  the  required  facial  movement.  
7.   Alexia:  loss  of  the  power  to  grasp  the  meaning  of  written  or  printed  words.  
8.   Alexia  without  agraphia  (Pure  word  blindness):  loss  of  ability  to  read  words,  
with   relative   preservation   of   ability   to   read   letters.   Spontaneous   writing   is   unimpaired,  
but  the  person  can’t  read  what  he  has  written.  Lesion:  Left  occipital  lobe,  Supplied  by  
posterior  cerebral  arteries.  
9.   Agraphia:  Inability  to  express  thoughts  in  writing.  
10.   Prosopagnosia:  Inability  to  recognise  familiar  faces.  
11.   Agnosia:   Inability   to   recognise   stimuli   that   were   formerly   recognised   despite  
intact   perception.   Can   be   auditory,   visual   or   tactile.   Non-­‐dominant   hemisphere  
lesions.  
12.   Gerstmann’s   Syndrome:   right-­‐left   disorientation,   Agraphia,   acalculia   and  
finger  agnosia.  Lesion:  left  angular  gyrus  (dominant  parietal  lobe)  
13.   Balint’s  syndrome:  inability  to  direct  the  eyes  to  a  certain  point  in  the  visual  
field   despite   intact   vision   and   eye   movements.   Lesion:   bilateral   parieto-­‐occipital  
cortex.  
14.   Anton’s   syndrome:   Denial   of   blindness   and   confabulation.   Lesion:   bilateral  
occipital  cortex.  
15.   Kluver-­‐Bucy   syndrome:   Blunted   affect   with   apathy,   visual   agnosia,   marked  
tendency   to   take   notice   and   attend   to   minute   visual   stimuli,   hyperorality,   docility,  
unusual  dietary  habits  and  hypersexuality.  Lesion:  bilateral  temporal  lobes.  

8
Paper A2: Neuroanatomy & Neurochemistry

16.   The   alien   hand   syndrome   is   the   unwilled   and   uncontrolled   action   of   one  
upper   limb.   There   is   loss   of   feeling   of   ownership   but   not   loss   of   sensation   in   the  
affected   hand.   Alien   hand   sign   should   be   reserved   for   cases   in   which   the   hand   feels  
foreign   together   with   observable   involuntary   motor   activity.   Originally   described   in  
callosal   tumours,   the   aetiology   of   alien   hand   also   includes   infarction   of   the   medial  
frontal   cortex,   occipitotemporal   lobe,   parietal   lobe   and   thalamus,   and   corticobasal  
degeneration.  
17.   Environmental   dependency   syndrome   (where   an   individual   has   an   excessive  
dependence   on   the   social   and   physical   environment)   is   a   feature   of   frontal   lobe  
syndrome.  
18.   Weber’s   Syndrome   constitutes   an   ipsilateral   third   nerve   paralysis   with   a  
contralateral   hemiplegia   due   to   mid-­‐brain   infarction   as   a   result   of   occlusion   of   the  
paramedian  branches  of  the  basilar  artery.  
19.   Kleine-­‐Levin  Syndrome:    This  is  a  rare  secondary  sleep  disorder  consisting  of  
episodes   of   somnolence   and   increased   appetite,   often   lasting   days   or   weeks   and   with  
long  intervals  of  normality  between  them  
1.4   Functions  of  the  major  Gyri:  
Precentral   area:   comprises   of   anterior   (secondary)   and   posterior   (primary)   regions  
and   concerned   with   voluntary   movements.   It   is   associated   with   contralateral  
movements,  for  example  in  the  limbs  or  bilateral  movements  in  the  upper  face.  There  
is  topographical  representation  of  the  body  in  the  primary  motor  cortex.  
Frontal  eye  field  are  associated  with  conjugate  eye  movements.  
Broca’s  speech  area  is  situated  in  the  dominant  cerebral  hemisphere  and  is  associated  
with  motor  aspect  of  speech.  
Prefrontal   cortex   is   concerned   with   personality,   depth   of   feeling,   initiative   and  
judgement.  
The  primary  sensory  area  is  situated  in  the  post  central  gyrus  and  is  associated  with  
sensations  of  the  contralateral  part  of  the  body.  
Fusiform   gyrus:   There   is   still   some   dispute   over   the   functionality   of   this   area   of   the  
temporal   lobe.     However   there   is   a   consensus   that   it   is   involved   with   processing   of  
colour  information,  facial  recognition,  word  recognition  and  number  recognition.  
1.5   Diencephalic  structures

Basal  Ganglia  

Refers  to  the  following  nuclei:  Caudate,  putamen,  globus  pallidus,  nucleus  accumbens,  
septi  and  olfactory  tubercle.  Caudate,  putamen,  globus  pallidus  together  are  called  the  
corpus  striatum.  The  role  of  basal  ganglia  in  motor  control  includes  the  preparation  for  
and   execution   of   cortically   initiated   movement.     The   basal   ganglion   also   has   roles   in  
cognition,  emotion,  and  motivation.  Lesions  in  parts  of  the  basal  ganglia  giving  rise  to  
individual  pathology  are:    
§ Caudate  nucleus  à  Chorea;    

9
Paper A2: Neuroanatomy & Neurochemistry

§ Subthalamic  nucleusà  Hemiballismus;    

§ Dopaminergic  nigrostriatal  system  à  Parkinsonism.  
Discrete   lesions   in   caudate   nucleus   are   more   likely   to   produce   behavioural  
disturbances,   whereas   discrete   lesions   in   the   putamen   are   more   likely   to   produce  
motor  disturbances.  

Figure:  Basal  Ganglia  and  its  connections2,3  

 
Limbic  system  

The   limbic   lobe   refers   to   the   structures   that   form   a   limbus   (ring   or   border)   around   the  
brain   stem.   It   is   connected   to   the   cortex,   hypothalamus,   thalamus   and   basal   ganglia.  
The   limbic   system   plays   an   important   role   in:   emotional   behaviour,   memory,  
homeostatic   responses,   sexual   behaviour   and   motivation.   It   contains   many   parts  
including:  
§ Cingulate  gyrus:  a  band  of  cortex  that  runs  from  the  front  of  the  brain  to  the  
back  
§ Parahippocampus  gyrus  
§ Dentate  gyrus  
§ Hippocampus  –  which  is  involved  in  memory  formation  &  storage  
§ Amgydala  –  involved  with  forming  complex  emotional  responses  
The   hippocampus   and   the   adjacent   limbic   structures   are   involved   in   anterograde  
memory  (acquisition  of  knowledge).  The  left  hippocampus  is  involved  in  acquisition  of  
new   verbal   knowledge,   and   the   right   hippocampus   is   involved   in   acquisition   of   new  
non-­‐verbal   memory.   The   basal   ganglia,   cerebellum   and   sensorimotor   cortices   are   all  
essential  in  this.  
The   temporal   lobes   contain   regions   that   specialise   in   face   and   object   recognition.  
Normally   these   face   recognition   areas   relay   information   to   the   limbic   system  
(specifically   the   Amygdala),   which   then   helps   to   generate   emotional   responses   to  
particular  faces.  
                                                                                                                         
2  [Link]  

3  [Link]  

10
Paper A2: Neuroanatomy & Neurochemistry

Fear   conditioning   is   a   form   of   classical   conditioning   that   involves   the   repeated  

pairing  of  a  non-­‐threatening  stimulus  such  as  a  light,  called  the  conditioned  stimulus,  
with   a   noxious   stimulus   such   as   a   mild   shock,   called   the   unconditioned   stimulus,   until  
the  animal  shows  a  fear  response  not  just  to  the  shock  but  to  the  light  alone,  called  a  
conditioned  stimulus.  Recent  research  has  supported  a  crucial  role  for  the  amygdala  in  
fear  conditioning.  If  a  rat  has  its  amygdala  destroyed,  it  will  still  show  a  fear  response  
to  the  foot  shock  but  fail  to  learn  the  association  between  the  light  and  the  foot  shock.  
Even   after   many   training   sessions,   the   animal   will   not   exhibit   any   fear   to   the   light  
alone.  Similar  response  is  seen  in  humans  with  amygdalar  lesions.  

 
4
Figure:  Limbic  system  
 
1.6   White  matter  pathways  
Corpus   Callosum:   is   the   largest   set   of   inter-­‐hemispheric   connecting   fibres   divided  
into  rostrum,  genu,  body  and  splenium.  Lesions  of  this  are  associated  with  acute  severe  
intellectual  deterioration.  Loss  of  contact  between  dominant  (left)  and  non-­‐dominant  
hemispheres   leads   to   left   sided   apraxia   to   verbal   commands   and   astereognosis   in   the  
left  hand.  
Fornix:  is  made  of  fibres  representing  the  hippocampus  efferent  system.  
Papez   circuit:   is   the   term   coined   by   James   Papez   in   1937   for   a   circle   of   connections  
from   the   hippocampus   to   the   mammillary   body,   to   anterior   thalamus,   to   cingulate  
cortex,   and   back   to   the   hippocampus   through   the   cingulum   and   parahippocampal  
gyrus.  Historically,  it  was  the  anatomic  basis  of  the  concept  of  the  limbic  system.  It  was  
believed  to  be  a  reverberating  circuit  that  formed  the  neuronal  mechanism  of  emotion.  
However  it  also  has  a  role  in  perception,  memory  and  different  types  of  behaviour.  
Figure:  Papez  circuit.  
 

                                                                                                                         
4  [Link]  

11
Paper A2: Neuroanatomy & Neurochemistry

Hippocampal  Formation   Cingulate  gyrus  

Mammilary  Body   Anterior  Nuclei  of  

Thalamus  

 
1.7   Cranial  nerves5:  

The  neuroanatomy  and  neurology  of  cranial  nerves  is  covered  under  this  section.  
Olfactory  (I)  Nerve  
• Anatomy  Olfactory  cells  are  a  series  of  bipolar  neurones  which  pass  through  
the  cribriform  plate  to  the  olfactory  bulb.  
• Signs  Reduced  taste  and  smell,  but  not  to  ammonia  which  stimulates  the  pain  
fibres  carried  in  the  trigeminal  nerve.  
• Causes  Trauma;  frontal  lobe  tumour;  meningitis.    
Optic  (II)  Nerve  
• Anatomy  The  optic  nerve  fibres  are  the  axons  of  the  retinal  ganglion  cells.  At  
the  optic  chiasm,  only  the  fibres  derived  from  the  nasal  parts  of  the  retina  
decussate,  join  with  the  non-­‐decussating  fibres  and  pass  backwards  in  their  
respective  optic  tracts  to  the  visual  cortex.    
Signs  and  causes  
• Visual  field  defects:  
Monocular  blindness:  Lesions  of  one  eye  or  optic  nerve  e.g.  MS,  giant  cell  
arteritis.    
Bilateral  blindness:  Methyl  alcohol,  tobacco  amblyopia;  neurosyphilis.  
Bitemporal  hemianopia:  Optic  chiasm  compression  e.g.  internal  carotid  artery  
aneurysm,  pituitary  adenoma  or  craniopharyngioma  
Homonymous  hemianopia:  Affects  half  the  visual  field  contralateral  to  the  lesion  
in  each  eye.  Lesions  lie  beyond  the  optic  chiasm  in  the  tracts,  radiation  or  
occipital  cortex  e.g.  stroke,  abscess,  tumour.    
• Pupillary  Abnormalities.  
• Optic  neuritis  (pain  on  moving  eye,  loss  of  central  vision,  afferent  pupillary  
defect,  papilloedema).  Causes:  demyelination;  rarely  sinusitis,  syphilis,  collagen  
vascular  disorders.  
• Optic  atrophy  (pale  optic  discs  and  reduced  acuity):  MS;  frontal  tumours.  
Papilloedema  (swollen  discs):  
                                                                                                                         
5  [Link]  

12
Paper A2: Neuroanatomy & Neurochemistry

1. Raised  ICP  (tumour,  abscess,  encephalitis,  hydrocephalus,  benign  

intracranial  hypertension);  
2. Retro-­‐orbital  lesion  (e.g.  cavernous  sinus  thrombosis);  
3. Inflammation  (e.g.  optic  neuritis);  
4. Ischaemia  (e.g.  accelerated  hypertension).    
Oculomotor  (III)  Nerve  
• Anatomy  This  nerve  emerges  from  the  brainstem  on  the  medial  aspect  of  the  
crus  cerebri  and  then  passes  forwards  between  the  posterior  cerebral  and  
superior  cerebellar  arteries,  very  close  to  the  posterior  communicating  artery.  It  
pierces  the  dura  near  the  edge  of  the  tentorium  cerebelli,  passes  through  the  
lateral  part  of  the  cavernous  sinus  with  the  IV  and  VI  nerves  to  enter  the  orbit.  
• Signs  The  initial  sign  is  often  a  fixed  dilated  pupil  which  doesn't  accommodate;  
then  ptosis  develops  and  then  a  complete  internal  ophthalmoplegia  (masked  by  
ptosis).  Unopposed  lateral  rectus  causes  outward  deviation  of  the  eye.  If  the  
ocular  sympathetic  fibres  are  also  affected  behind  the  orbit,  the  pupil  will  be  
fixed  but  not  dilated.  
• Causes  of  a  single  III  lesion  Diabetes  mellitus;  giant  cell  arteritis;  syphilis;  
posterior  communicating  artery  aneurysm;  idiopathic;  Raised  ICP  if  causes  
uncal  herniation  through  the  tentorium  -­‐  this  compresses  the  nerve.  Third  
nerve  palsies  without  a  dilated  pupil  are  due  to  diabetes  mellitus  or  another  
vascular  cause.  Early  dilatation  of  a  pupil  implies  a  compressive  lesion.  Diplopia  
from  a  third  nerve  lesion  may  cause  nystagmus.    
Trochlear  (IV)  Nerve  
• Anatomy  Passes  backwards  in  the  brainstem,  decussates  in  the  anterior  
medullary  velum  and  emerges  to  pass  round  the  cerebral  peduncle  between  it  
and  the  temporal  lobe,  passing  over  the  tentorium  to  enter  the  cavernous  sinus  
with  II  and  VI,  and  enters  the  orbit  to  supply  the  superior  oblique.  
• Signs  Diplopia  due  to  weakness  of  downward  and  inward  eye  movement.  
Commonest  cause  of  a  pure  vertical  diplopia.  Patient  tends  to  compensate  by  
tilting  head  towards  the  affected  side.  
• Causes  of  a  single  IV  lesion  Rare  and  most  commonly  due  to  trauma  to  the  
orbit.  May  also  occur  in  diabetes  or  infarction  secondary  to  hypertension.    
Trigeminal  (V)  Nerve  
• Anatomy  Forms  three  trunks:  ophthalmic,  maxillary  and  mandibular  divisions.  
The  latter  contains  both  sensory  and  motor  fibres.  There  may  be  considerable  
individual  variation  in  the  exact  areas  of  skin  supplied.  
s Ophthalmic  division  lies  with  III,  IV  and  VI  in  the  cavernous  sinus  and  
supplies  the  skin  over  the  medial  nose,  forehead,  eye  (including  corneal  
reflex).  
s Maxillary  division  passes  through  the  inferior  part  of  the  cavernous  sinus  
and  the  foramen  rotundum  and  joins  with  parasympathetic  fibres  to  
form  the  sphenopalatine  ganglion  (lacrimation).  It  then  enters  the  orbit  
as  the  infraorbital  nerve,  eventually  supplying  the  skin  of  the  upper  lip,  
cheek  and  triangle  of  skin  extending  from  the  angle  of  eye  and  mouth  to  
an  apex  in  the  mid  temporal  region.  
s Mandibular  division  Leaves  the  skull  through  the  foramen  ovale  carrying  
sensory  fibres  from  the  skin  of  the  lower  lip  and  chin  up  to  and  

13
Paper A2: Neuroanatomy & Neurochemistry

including  the  tragus  and  upper  part  of  the  pinna;  mucus  membranes  of  
floor  of  the  mouth,  cheek  and  anterior  two-­‐thirds  of  the  tongue  (taste  
fibres  joining  it  from  the  chorda  tympani  branch  of  the  facial  nerve).  
Motor  fibres  supply  the  masseter,  temporalis,  pterigoids.  
• Signs  Reduced  sensation  or  dysasthesia  over  affected  area.  Weakness  of  jaw  
clenching  and  side  to  side  movement.  If  there  is  a  LMN  lesion,  the  jaw  deviates  
to  the  weak  side  when  the  mouth  is  opened.  There  may  be  fasiculation  of  
temporalis  and  masseter.  
• Causes  of  a  single  V  lesion    
o Sensory:  Trigeminal  Neuralgia,  Herpes  zoster,  nasopharyngeal  
carcinoma.  
o Motor:  Bulbar  palsy,  acoustic  neuroma.    
 
Abducent  (VI)  Nerve  
• Anatomy  From  the  nucleus  in  the  floor  of  the  forth  ventricle  fibres  pass  
forward  in  the  pons  and  emerge  to  follow  a  long  extracerebral  course  on  the  
base  of  the  brain,  across  the  apex  of  the  petrous  temporal,  through  the  posterior  
fossa  near  the  dorsum  sellae  to  enter  the  cavernous  sinus  and  thence  to  the  
orbit  and  lateral  rectus.  
• Signs  Inability  to  look  laterally.  Eye  is  deviated  medially  because  of  unopposed  
action  of  medial  rectus.  
• Causes  of  a  single  VI  lesion  MS,  pontine  CVA.  It  is  considered  a  false  
localizing  sign  (because  of  long  extracerebral  course)  in  raised  ICP.  
Facial  (VII)  Nerve  
• Anatomy  Mainly  motor  (some  sensory  fibres  from  external  acoustic  meatus,  
fibres  controlling  salivation  and  taste  fibres  from  the  anterior  tongue).  Fibres  
loop  around  the  VI  nucleus  before  leaving  the  pons  medial  to  VIII  and  passing  
through  the  internal  acoustic  meatus.  It  passes  through  the  petrous  temporal  in  
the  facial  canal,  widens  to  form  the  geniculate  ganglion  (taste  and  salivation)  on  
the  medial  side  of  the  middle  ear  whence  it  turns  sharply  (and  the  chorda  
tympani  leaves),  to  emerge  through  the  stylomastoid  foramen  to  supply  the  
muscles  of  facial  expression.  
• Signs  Facial  weakness.  In  a  LMN  lesion  the  forehead  is  paralysed  -­‐  the  final  
common  pathway  to  the  muscles  is  destroyed;  whereas  the  upper  facial  muscles  
are  partially  spared  in  an  UMN  lesion  because  of  alternative  pathways  in  the  
brainstem.  There  appear  to  be  different  pathways  for  voluntary  and  emotional  
movement.  CVA's  usually  weaken  voluntary  movement  often  sparing  
involuntary  movements  (e.g.  spontaneous  smiling).  The  much  rarer  selective  
loss  of  emotional  movement  is  called  mimic  paralysis  and  is  usually  due  to  a  
frontal  or  thalamic  lesion.  
• Causes  of  a  single  VII  lesion    
o LMN:  Bell's  palsy,  polio,  otitis  media,  skull  fracture,  cerebello-­‐pontine  
angle  tumours,  parotid  tumours,  Herpes  zoster  (Ramsay-­‐Hunt  
syndrome),    
o UMN:  (spares  the  forehead  -­‐  bilateral  innervation)  Stroke,  tumour.    
Vestibulocochlear  (VIII)  Nerve  

14
Paper A2: Neuroanatomy & Neurochemistry

• Anatomy  Carries  two  groups  of  fibres,  those  to  the  cochlea  (hearing)  and  to  the  
semicircular  canals,  utricle  and  saccule  (balance  and  posture).  They  pass,  
together  with  the  facial  nerve,  from  the  brainstem  across  the  posterior  fossa  to  
the  internal  acoustic  meatus.  
• Signs  Unilateral  sensorineural  deafness,  tinnitus.  Slow  growing  lesions  seldom  
present  with  vestibular  symptoms  as  compensation  has  time  to  occur.  
• Causes  of  a  single  VIII  lesion  loud  noise;  Ménière's  disease;  Herpes  zoster;  
neurofibroma,  acoustic  neuroma,  brainstem  CVA.  
Glossopharyngeal  (IX)  Nerve  
• Anatomy  Contains  sensory,  motor  (stylopharyngeus  only)  and  parasympathetic  
fibres  (salivary  glands).  Passes  across  the  posterior  fossa,  through  the  jugular  
foramen  and  into  the  neck  supplying  tonsil,  palate  and  posterior  third  of  
tongue.  
• Signs  Unilateral  lesions  do  not  cause  any  deficit  because  of  bilateral  cortico-­‐
bulbar  connections.  Bilateral  lesions  result  in  pseudo-­‐bulbar  palsy.  These  nerves  
are  closely  interlinked.  
• Causes  (single  nerve  lesions  exceedingly  rare)  Trauma,  brainstem  lesions,  
cerebello-­‐pontine  angle  and  neck  tumours,  polio,  Gullain-­‐Barre.    
Vagus  (X)  
• Anatomy  The  vagus  nerve,  "the  wanderer",  contains  motor  fibres  (to  the  palate  
and  vocal  cords),  sensory  components  (posterior  and  floor  of  external  acoustic  
meatus)  and  visceral  afferent  and  efferent  fibres.  It  leaves  the  skull  through  the  
jugular  foramen,  passes  within  the  carotid  sheath  in  the  neck  (giving  off  cardiac  
branches,  and  the  recurrent  laryngeal  nerves  supplying  the  vocal  cords),  
through  the  thorax  supplying  lungs,  and  continues  on  via  the  oesophageal  
opening  to  supply  the  abdominal  organs.  
• Signs  Palatal  weakness  can  cause  "nasal  speech"  and  nasal  regurgitation  of  food.  
The  palate  moves  asymmetrically  when  the  patient  says  "ah".  Recurrent  nerve  
palsy  results  in  hoarseness,  loss  of  volume  and  "bovine  cough".  
• Causes  (single  nerve  lesions  exceedingly  rare)  Trauma,  brainstem  lesions,  
tumours  in  the  cerebello-­‐pontine  angle,  jugular  foramen  and  neck;  polio,  
Gullain-­‐Barre.    
Spinal  Accessory  (XI)  
• Anatomy  Motor  to  sternocleidomastoid  and  trapezius.  
• Signs  weakness  and  wasting  of  these  muscles.  
• Causes  as  vagus  above.    
Hypoglossal  (XII)  
• Anatomy  It  passes  briefly  across  the  posterior  fossa,  leaves  the  skull  through  
the  hypoglossal  canal  and  supplies  motor  fibres  to  the  tongue  and  most  of  the  
infrahyoid  muscles.  
• Signs  A  LMN  lesion  produces  wasting  of  the  ipsilateral  side  of  the  tongue,  with  
fasiculation;  and  on  attempted  protrusion  tongue  deviates  towards  affected  
side,  but  the  tongue  deviates  away  from  the  side  of  a  central  lesion.  
• Causes  of  a  single  XII  lesion:  Rare.  TB,  median  branch  thrombosis  of  the  
vertebral  artery.    
Combined  cranial  nerve  lesions    
• VII,  VIII,  then  V  and  sometimes  IX:  cerebellopontine  angle  tumours.  

15
Paper A2: Neuroanatomy & Neurochemistry

V,  VI  (Gradenigo's  syndrome):  lesions  within  the  petrous  temporal  bone.  

•
Combined  III,  IV,  VI:  stroke,  tumours,  Wenicke’s  encephalopathy,  aneurysms,  
•
MS,  myasthenia  gravis;  meningitis,  cavernous  sinus  thrombosis,  Guillain-­‐Barre  
etc.  
CSF:  The  normal  CSF  findings  include  CSF  pressure  of  60-­‐200  H2O,  glucose  of  60-­‐80  
mg/dl   (2/3   blood   glucose),   Protein   of   20-­‐45   mg/dl,   Chloride   of   116   –122,   contains   no  
neutrophils  and  up  to  five  lymphocytes.  
Major  neurochemical  pathways  
Nigrostriatal  system:  originates  from  substantia  nigra  to  the  corpus  striatum  and  is  
associated  with  sensorimotor  coordination.  
Mesolimbic   and   mesocortical   system   :   orginates   from   ventral   tegmental   area   with  
mesolimbic   pathways   projecting   to   limbic   system   and   the   mesocortical   projecting   to  
cingulate,  entorhinal  and  medial  prefrontal  cortex.  
Locus   coeruleus:   has   the   greatest   density   of   noradrenergic   neurones,   with   at   least   5  
noradrenergic  tracts.  3  of  them  ascend  in  the  medial  forebrain  bundle  to  supply  mainly  
the   ipsilateral   cerebral   cortex,   thalamus,   hypothalamus,   limbic   system   and   olfactory  
bulb.   The   fourth   supplies   cerebellar   cortex   by   superior   cerebellar   peduncle.   The   fifth  
noradrenergic  tract  descends  in  the  mesencephalon  and  spinal  cord.  
Cholinergic   pathways   include   central   ascending   pathways   to   limbic   system,  
hypothalamus,   thalamus,   cerebellum   and   cerebral   cortex.   Ascending   reticular  
pathways  of  hippocampus  are  also  cholinergic.  
The  main  central  nuclei  containing  serotonin  are  brainstem  raphe  nuclei.  
1.8   The  Blood  supply  of  the  brain  
The   brain   is   supplied   by   two   separate   systems   of   vasculature:   the   carotid   system   and  
the  vertebral  system.  The  carotid  system  supplies  the  frontal  and  parietal  lobe,  all  but  
the  inferior-­‐posterior  third  of  the  temporal  lobe,  the  hypothalamus,  basal  ganglia  and  
the   eyes.     Symptoms   of   carotid   system   disturbance   include   apraxia,   agnosia,   aphasia,  
impairment   of   constructional   &   spatial   skills,   emotional   abnormalities   and/or  
delusions.  

The  vertebral  system  supplies  the  posterior  temporal  lobe,  occipital  lobe,  upper  part  
of   the   spinal   cord,   brainstem,   midbrain,   thalamus,   cerebellum   and   the   inner   ear.  
Symptoms   of   vertebral-­‐basilar   system   disturbance   include   ataxia,   nystagmus,   cranial  
nerve   signs,   internuclear   ophthalmoplegia,   dissociated   sensory   loss   and/or   bilateral  
abnormalities.  

16
Paper A2: Neuroanatomy & Neurochemistry

 
System   Branche Areas  supplied   Impairment  
s  
Internal   Anterior   Orbital  frontal  lobes,   Unilateral:  Contralateral  
Carotid   cerebral   postr  portion  of  medial   hemiplegia  (leg  >  face  &  arm),  
artery  *   artery   cerebrum,  anterior  four   contralateral  sensory  deficit,  &  
fifths  of  corpus  callosum,   transcortical  motor  aphasia.  
head  of  caudate  &   Bilateral:  Apathy,  akinetic  
putamen.   mutism,  loss  of  sphincter  
control,  release  reflexes,  memory  
&  emotional  disturbance    
Middle   Lateral  Part  of  cerebrum,   Contralateral  hemiplegia  (face  &  
cerebral   frontal  lobe,  motor  areas,   arm  >  leg),  sensory  deficits,  
artery   superior  (sensory)  &   homonymous  hemianospia  or  
inferior  parietal  regions,   infr  quandrantanopia,  Aphasia,  
superior  portion  of   Gerstmann’s  syndrome.  If  left  
temporal  lobe  &  insula   hemisphere  à  global  aphasia.  
{Broca’s  &  Wernicke’s)   Rightà  neglect,  denial,  
confabulation,  manic-­‐like  states,  
visuo-­‐perceptual  abnormalities.    
Ophthal Postr  limb  of  internal   Monocular  blindness,  Visual  
mic   capsule,  third  ventricle,   acuity  impairment.  
artery   portions  of  optic  chiasm.  
Anterior   Medial  portion  of  globus   Contralateral  motor  deficit,  
Choroidal   pallidus  &  parts  of   contralateral  hemisensory  deficit  
internal  capsule.   &  visual  field  deficit.  
Vertebr Vertebral   Medulla,  postr  infr   Cerebellar  signs,  cranial  nerve  
al   arteries   cerebellum   signs,  stupor  or  coma,  crossed  
artery   motor  &  sensory  signs,  illusions,  
  visual  hallucinations.  
Basilar   Pons,  cerebellum  
artery  
Posterior   Hippocampus,  medial   Unilateral:  contralateral  
cerebral   temporal  lobes,  occipital   hemianopia  with  macular  
arteries   lobe,  thalamus,   sparing,  visual  agnosia,  
subthalamic  nuclei,   contralateral  sensory  loss  with  
substantia  nigra,   concomitant  pain  (thalamic  
midbrain,  pineal  body.   syndrome)  &  Alexia  without  
agraphia.  Bilateral:  Cortical  
blindness,  Prosopagnosia,  Balint  
syndrome,  Anton’s  syndrome,  
agitated  delirium  &  Memory  
loss.  

*Unilateral  blindness  is  the  only  feature  distinguishing  the  carotid  syndrome  from  that  
produced  by  obstruction  of  the  middle  cerebral  artery.  

17
Paper A2: Neuroanatomy & Neurochemistry

II.   Neurochemistry  

Receptors  
There   are   two   main   types   of   receptors:   ionotropic   receptors   and   metabotropic  
receptors.  Ionotropic  receptor  effects  act  immediately  and  last  10-­‐20msec,  faster  then  
metabotropic  effects  which  can  take  up  to  30msec  to  start  and  can  last  for  as  long  as  a  
second.  
The   ionotropic   receptor,   means   ‘directed   towards   ions’.   In   ionotropic   receptors,  
neurotransmitter   binding   leads   to   the   opening   of   a   transmembrane   channel   that  
allows   passage   of   ions,   for   example   when   glutamate   binds   to   its   receptor   it   opens  
sodium   gates   enabling   Na+   to   enter   the   neuron,   thereby   depolarising   the   membrane.  
Glutamate   is   therefore   an   excitatory   neurotransmitter.   The   GABA-­‐A   receptor   is  
associated   with   a   chloride   (Cl-­‐)   channel,   it   is   therefore   inhibitory.   Other   examples  
include  NMDA  receptors,  nicotinic  receptors  (acetylcholine),  and  5HT3.  
A  metabotropic  receptor  influences  the  activity  of  a  cell  indirectly  by  first  initiating  a  
metabolic   change   in   the   cell.   When   a   neurotransmitter   binds   to   a   metabotropic  
receptor  a  chain  of  reactions  are  set  into  motion,  by  stimulating  the  membrane  bound  
G   protein.   The   end   result   of   these   reactions   may   be   to   alter   the   shape   of   the   cell  
slightly,  change  the  way  in  which  the  neuron  makes  certain  proteins  or  even  to  open  
ion   channels.   Examples   include   Dopamine   receptors   (D1   –   D5),   GABAB,   serotonin  
receptors  (except  5HT3),  Muscarinic  acetylcholine  receptors  (M1,  M2,  M3,  Noradrenaline  
receptors  (both  alpha  and  beta  subtypes  types).  
 
Small  molecule  neurotransmitters  
Type   Neurotransmitter   Postsynaptic  effect  
  Acetylcholine   Excitatory  
Amino  acids   Gamma  aminobutyric  acidGABA   Inhibitory  
Glycine   Inhibitory  
Glutamate   Excitatory  
Aspartate   Excitatory  
Biogenic  amines   Dopamine   Excitatory  
Noradrenaline   Excitatory  
Serotonin   Excitatory  
Histamine   Excitatory  
Neuropeptide  neurotransmitters  
Corticotropin  releasing  hormone  
Corticotropin  (ACTH)  
Beta-­‐endorphin  
Substance  P  
Neurotensin  
Somatostatin  
Bradykinin  
Vasopressin  
Angiotensin  II  

18
Paper A2: Neuroanatomy & Neurochemistry

2.1   Monoamine  Neurotransmitters:    

Includes  Dopamine,  serotonin,  noradrenaline,  acetylcholine  and  Histamine.  
Synthesis:      
Tyrosine  
  Tyrosine  hydroxylase  
(rate  limiting)  
 
   Dopa                                                                  

  MAO  A  or  MAO  B  

Dopa   Catechol  –  O  –  methyl  
decarboxylase   transferase  
 

Dopamine                                                            Released  into  synapse                                                      Metabolites  

                                                                                                                                                    Mainly  MAO  A  
Dopa  β   and  
 
hydroxylase   Catechol  –  O  –  methyl  
  transferase  

Adrenalin                  Noradrenalin                Released  into  synapse                                    Metabolites  

 
All  the  monoamines  (dopamine,  Noradrenaline  and  serotonin)  are  metabolised  by  the  
monoamine  oxidase  enzymes.  
2.2   Dopamine:    
There  are  two  groups  of  dopamine  receptors  that  have  been  elucidated:  the  D1  receptor  
group  (D1  &  D5)  and  the  D2  receptor  group  (D2,  D3  &  D4).  The  typical  antipsychotics  
exert   their   actions   by   antagonism   of   the   postsynaptic   D2   receptors,   whereas   the  
atypical   drugs   act   by   blocking   the   D2   receptors   and   also   blocking   5HT2   receptors.  
Clozapine   has   more   affinity   for   the   D4&   D1   receptors   compared   to   the   other  
antipsychotics   (typical   &   atypical).   It   also   has   the   highest   affinity   for   the   5HT2  
receptors   compared   to   other   antipsychotics.   Aripiprazole   is   a   partial   agonist   at   D2  
receptors   (in   the   absence   of   dopamine   it   acts   as   a   weak   agonist),   an   antagonist   at  
5HT2A  receptors  and  a  partial  agonist  at  5HT1A  receptors.  
 
   

19
 Paper A2: Neuroanatomy & Neurochemistry

Table:  Dopamine  receptors  and  action  summary  

Receptor   Type  and   Action   Effect   Class  of  Drugs   Drug  

physiolog
y  
       
Atypical   Clozapine  
D1   G-­‐‑protein   Antagonist   Increase  mood  
antipsychotics   Olanzapine  
D1  like  
    Aripiprazole  
Partial   Can  be  activating,   Atypical  
    Low  dose  
agonist   cause  agitation   antipsychotics  
    sulpiride  
      Mesolimbic  pathway  =   Typical   All,  especially  
      Reduces  positive   antipsychotics   haloperidol  
      symptoms  of      
      schizophrenia      
D2   G-­‐‑protein         Aripiprazole  
D2  -­‐‑like   Antagonist   Mesocortical  pathway   Atypical   Clozapine  
=     antipsychotics   Olanzapine  
Induces  negative  and     Risperidone  
affective  symptoms    
 
Nigrostriatal  pathway  
=  EPSEs  
 
Tuberoinfundibular  
pathway  =  Ó  
Prolactin  
  Olanzapine  
Atypical  
D3   G-­‐‑protein   Antagonist     Clozapine  
  antipsychotics   Sulpiride  
D2  -­‐‑  like  
Amisulpiride  

D4   G-­‐‑protein   Antagonist     Atypical   Clozapine  

D2  -­‐‑  like   antipsychotics   Olanzapine  

D5   G-­‐‑  protein   Not  currently  implicated  in  psychiatric  medication  action  

D1-­‐‑like  

 
Antidepressants   Sertraline  
 
Re-­‐‑uptake  inhibition   Cocaine  
Drugs  of  abuse  
Amphetamines  

St  John’s  wort  
Other  
Bupropion  

   
SSRIs  
20
  Antidepressants  
Paper A2: Neuroanatomy & Neurochemistry

  Venlafaxine  
Dopamine  transport  inhibitor   Duloxetine  
Trazadone  

Drug  of  abuse   Cocaine  

Other   Modafinil  
 
 
2.3   Noradrenaline:    
There   are   two   types   of   adrenoceptors   –   α   (1   &   2)   and   β   (1   &   2).   Both   these   types   of  
receptors   are   metabotropic.   The   α1   receptors   are   postsynaptic   excitatory   receptors,  
whereas  α2  receptors  are  inhibitory  and  are  found  both  as  both  pre  and  postsynaptic  
receptors.  The  β  adrenoceptors  are  mostly  postsynaptic.  (β1  à  heart  increases  rate  and  
force  of  cardiac  contraction,  β2à  brochodilatation).  Presynaptic  β1  receptors  facilitate  
noradrenaline  release,  whereas  presynaptic  β2  receptors  are  inhibitory.  
The   ‘amine   hypothesis   of   depression’   à   a   reduction   in   the   functional   efficiency   of  
neurotransmission   at   synapses   (either   by   blocking   the   reuptake   or   presynaptic   or  
postsynaptic   blockade)   is   accompanied   by   increased   postsynaptic   sensitivity   to   the  
monoamines.  
Reboxetine   is   a   presynaptic   α2   antagonists   and   a   noradrenergic   reuptake   inhibitor  
(NARI).  
 
2.4   Serotonin:    
There  are  7  serotonin  receptors  (5HT1  –  5HT7)  with  more  than  15  subtypes.  All  the  5HT  
receptors  except  5HT3  receptors  are  metabotropic  
Pindolol,   a   5-­‐HT1A   antagonist,   has   some   utility   in   increasing   the   onset   of   therapeutic  
benefits   for   serotonin   reuptake   inhibitors.   It   blocks   both   pre   and   post   synaptic   5HT  
receptors.  Buspirone  is  a  5-­‐HT1A  agonist  that  is  useful  in  the  management  of  anxiety.    
A   brief   summary   of   some   of   the   receptor   subtypes   and   function   is   given   in   the   table  
below.  
 
   

21
Paper A2: Neuroanatomy & Neurochemistry

Receptor   Type  and   Action   Effect   Class  of  Drugs   Drug  

physiology  
       
Clozapine  
1   Atypical  
Partial   Increase   Quetiapine  
G-­‐‑protein   antipsychotics  
agonist   mood   Aripiprazole  
linked  
Other   Buspirone  
   
Agonist   Hallucinati LSD  
    Drugs  of  abuse  
ons   Ecstasy  
   
2A   G-­‐‑protein     Reduces   Aripiprazole  
linked     positive   Atypical   Clozapine  
Antagonist   symptoms   antipsychotics   Olanzapine  
of   Risperidone  
schizophre
Antidepressants   Mirtazapine  
nia  
  trazadone  
       
Quetiapine  
        Atypical  
Olanzapine  
2C   G-­‐‑protein   Antagonist   Increase   antipsychotics  
Clozapine  
linked   weight    
  SSRIs  
Antidepressants   Mirtazapine  
Trazadone  

  Atypical  
Ligand   Olanzapine  
3   Antagonist   Nausea   antipsychotics  
gated  ion  
Diarrhoea  
channel   Antidepressant   Mirtazapine  

6   G-­‐‑  protein   Antagonist     Improved   Atypical   Olanzapine  

linked   cognition   antipsychotics   Quetiapine  
and  
memory  
   
G  –  protein   Linked  to   Atypical   Quetiapine  
7   Antagonist    
linked   circadian   antipsychotics   Risperidone  
rhythm  
and  sleep  

Irreversible   Antidepressants   MAOIs  apart  

Monoamine  oxidase  
from  
inhibition  
moclobemide  

Reversible   Antidepressants   Moclobemide  

   
SSRIs  
 
Antidepressants   Venlafaxine  
 
Duloxetine  
Re-­‐‑uptake  inhibition  
22
Paper A2: Neuroanatomy & Neurochemistry

Trazadone  

Drug  of  abuse   Cocaine  

Other   St  John’s  Wort  

 
 
2.5   Histamine  
Is  implemented  in  regulating  wakefulness.  It  is  broken  down  intracellularly.    
 
  Histidine  
decarboxylase   MAO  B  
 
Histidine                        Histamine                    N-­‐‑methyl-­‐‑histamine                                        Inactive  metabolite  
 
 
Receptor( Type(and( Action( Effect( Class(of(Drugs( Drug(
physiology(
All!atypicals!
Typical!
except!
antipsychotics!
haloperidol!
!
H1( G#protein! Antagonist! Weight!gain!
Clozapine!
coupled! Drowsiness! Atypical!
Olanzapine!
antipsychotics!
Quetiapine!
Mirtazapine!
Antidepressants!
trazadone!
 
 
 
2.6   Acetylcholine:    
Two   types   of   receptors   –   Muscarinic   (M1   –   M5)   and   Nicotinic.   The   Muscarinic  
receptors   act   by   either   stimulating   Phosphatidylionositol   or   inhibiting   adenyl   cyclase  
(metabotropic   receptors),   whereas   nicotinic   receptors   are   involved   in   fast   excitatory  
synaptic  transmission  and  are  directly  coupled  to  cation  channels.  
The  M1  receptors  are  implicated  in  memory  and  learning  process.  Striatal  M4  receptors  
à  targets  for  anticholinergics  used  as  antiparkinson  agents.  

23
! Paper A2: Neuroanatomy & Neurochemistry

Receptor( Type(and( Action( Effect( Class(of(Drugs( Drug(

physiology(

All!atypicals!
Constipation! Typical!
except!
M1( G#protein! Antagonist! antipsychotics!
Blurred! haloperidol!
(muscarinic)( coupled!
vision! !

Dry!mouth! Atypical! Clozapine!

antipsychotics!
Cognitive! Olanzapine!
impairment!
Quetiapine!
Sedation!
Antidepressants! Tricyclics!

May!affect!
M3( G#protein! Antagonist! Atypical! Clozapine!
(muscarinic)( insulin!
coupled! antipsychotics!
secretion! Olanzapine!

Prevents!
α4β2( Ligand# Smoking!
Partial!agonist! bursts!of! Veranacline!
(nicotinic)( gated!ion! dopamine! cessation!
channel!
release!

! Possibly!
Positive!allosteric!
α7((nicotinic)( enhanced! Dementia!drugs! Galantamine!
modulator!(PAM)!
cognition!

Donepezil!
Reversible! Dementia!drugs!
Acetylcholinesterase(
inhibition( Galantamine!

Pseudoirreversible! Dementia!drugs! Rivastigmine!

Butylcholinesterase(inhibition( Dementia!drugs! Rivastigmine!

 
 
2.7   Amino  acid  neurotransmitters:    
Includes   inhibitory   transmitters   (GABA   &   Glycine)   and   excitatory   transmitters  
(glutamate  &  Asparatate).  
GABA:   GABA   exerts   its   inhibitory   effects   by   binding   to   two   distinct   receptors,   GABA-­‐
A   and   GABA-­‐B.   The   GABA-­‐A   receptors   form   a   Cl-­‐   channel.   The   binding   of   GABA   to  
GABA-­‐A  receptors  increases  the  Cl-­‐  conductance  of  presynaptic  neurons.  The  GABA-­‐B  
receptors  are  coupled  to  an  intracellular  G-­‐protein  and  act  by  increasing  conductance  
of  an  associated  K+  channel.    
The   anxiolytic   drugs   of   the   benzodiazepine   family   exert   their   soothing   effects   by  
potentiating   the   responses   of   GABA-­‐A   receptors   to   GABA   binding.   Buprenorphine   is  
generally  described  as  a  mixed  agonist-­‐antagonist  acting  mainly  as  a  partial  agonist  at  
mu  opioid  receptors,  with  some  antagonist  activity  at  kappa  receptors.  

24
Paper A2: Neuroanatomy & Neurochemistry

NMDA  receptor:  Is  a  ligand  gated  ion  channel  that  has  three  characteristic  features:  
Blocked   by   Magnesium;   significant   Calcium   ions   enter   the   cell   interior   during  
activation   of   the   receptor   and   NMDA   activated   neurotransmission   occurs   slowly   and  
lasts  for  a  long  period.  Exogenous  NMDA  agonists  (Lathyrus  satirus)  and  glutamate  are  
established  neurotoxins.  
Memantine   is   a   specific,   uncompetitive   NMDA   antagonist,   which   belongs   to   a   new  
class   of   drugs   for   the   treatment   of   dementia.   Phencyclidine   is   a   NMDA   antagonist.  
Acamprosate   is   a   GABA   analogue,   which   stimulates   the   GABAergic   inhibiting  
transmission   and   is   antagonistic   of   the   transmission   of   excitatory   aminoacids   (e.   g.  
glutamate).   There   has   been   a   lot   of   recent   interest   in   the   role   of   glutamate   in   the  
aetiology  of  schizophrenia.  It  has  been  found  that  glutamatergic  markers  are  decreased  
and   there   is   a   reduced   expression   of   NMDA   glutamate   receptors   in   the   medial  
temporal  lobes  of  schizophrenic  patients.  

Receptor( Type(and( Action( Effect( Class(of(Drugs( Drug(

physiology(

Drugs!of!abuse! Heroin!
Analgesia!
Full!agonist! Respiratory! Drug!substitution! Methadone!
Μ(opioid( G#protein!
coupled! depression!
Euphoria! Other! Alcohol!
Dependence!!
!
Partial!agonist! Drug!substitution! Buprenorphine!
Dopamine! Drugs!of!abuse! Cannabis!
G#protein!
Cannabinoid( Agonists! release!in!
coupled! Other! Alcohol!
reward!circuit!!
Phencyclidine!
NMDA( Ligand# Drugs!of!abuse! (PCP)!
Antagonism! Hallucinations!
(glutamate( gated!ion! Ketamine!
Anaesthesia!
receptor)( channel!
Dementia!Drugs! Memantine!
Other! Alcohol!
Ligand# Positive!
Anxiolytic! Anxiolytics! Benzodiazepines!
GABABA( gated!ion! allosteric!
Anticonvulsant!
channel! modulators! Other! Alcohol!  
Enhance!GABA!
GABA(B(B(
  G#!coupled! Antagonism! Other! Alcohol!
action!
References  
1. Companion   to   psychiatric   studies.   8th   edition,   2010,   Churchill   Livingstone,  
Edinburgh,  UK.  
2. New  Oxford  Textbook  of  Psychiatry,  eds  Gelder,  Lopez-­‐Ibor  Jr,  Andreason,  2000  
3. Gelder,   M.,   Mayou,   R.,   &   Cowen,   P.   (2001).     Shorter   Oxford   Textbook   of  
psychiatry.  Oxford  university  press.  Oxford.  
4. Hope,   R.   A.,   Longmore,   J.M.,   McManus,   et   al.   (1999).   Oxford   handbook   of   Clinical  
Medicine.  Oxford  University  Press.  Oxford.  
5. Puri   &   Tyrer   .   (1998)   Sciences   basic   to   Psychiatry,   2nd   edition,   Companion   to  
psychiatric  studies.  Churchill  Livingstone,  Edinburgh,  UK.  

25