Transcript Brain Structure and Function

 Lobes of the brain (forebrain)
 Midbrain/ Hindbrain
 Protection and Blood Supply
 Structure and Functions of a Neuron
 Synaptic Transmission
 Neurotransmitters
 The central nervous
system consists of the
brain and the spinal
cord and is responsible
for our basic functions,
personality and
behaviour.
 Cerebrum and Cerebral cortex
 Left and Right Hemispheres
 Left hemisphere for most people is the dominant
hemisphere- responsible for production of language,
mathematical ability, problem solving, logic
 Right hemisphere thought to be responsible for
creativity and spatial ability
 Most complex organ in
the body
 Weighs 1,300 grams
 Contains billions of
neural networks that
interact to create human
behaviour
 The major sections of the
cerebral hemispheres are
divided up into lobes.
 The lobes are named
after the bones of the
skull that overlie them
 Frontal Lobe
 Temporal Lobe
 Parietal Lobe
Barlow and Durand 2005
 Occipital Lobe
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Located at the front of both cerebral hemispheres
Primary motor cortex
Pre-motor cortex
Broca’s Area- Motor Production of speech
Complex Functioning
Personality
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judgement
Insight
Reasoning
problem solving,
abstract thinking
working memory
 Located behind the temporal lobe
 Sensory information
 Temperature
 Pain
 Texture
 Spatial orientation
 Perception
 Recognising object by touch
 Links visual and sensory information together
 Neglect
 Auditory information
 Higher order visual information
 Complex memory
 Memory of faces
 Comprehension of language
(Wernicke’s area)
http://www.nidcd.nih.gov/health/voice/aphasia.asp)
 Rearmost portion of the brain
 Visual processing area
 Corpus Callosum- Fibre bundle in the brain that
connects the two hemispheres together.
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Hypothalamus
Thalamus
Cerebellum
Pons
Medulla Oblongata
Reticular formation
Basal Ganglia
Substantia Nigra
Amygdala
Hippocampus
 Thalamus
 filters sensory
information, controls
mood states and body
movement associated with
emotive states
(http://training.seer.cancer.gov/module_anatom
y/unit5_3_nerve_org1_cns.html)
 Hypothalamus
 Central control’ for
pituitary gland. Regulates
autonomic, emotional,
endocrine and somatic
function. Has a direct
involvement in stress and
mood states.
 Cerebellum
 regulates equilibrium, muscle tone, postural control,
fine movement and coordination of voluntary muscle
movement.
 Pons
 Relay station between cerebrum and cerebellum
www.deryckthake.com/psychim
ages/hindbrain.
 Medulla oblongata
 Conscious control of skeletal
muscles, balance, co-ordination
regulating sound impulses in the
inner ear, regulation of automatic
responses such as heart rate,
swallowing, vomiting, coughing
and sneezing
 Reticular Formation Important in arousal and
maintaining consciousness,
alertness attention and Reticular
Activating System which controls
all cyclic functions i.e.
respiration, circadian rhythm.
 Basal Ganglia
Control of muscle tone,
activity, posture, large
muscle movements and
inhibit unwanted muscle
movements.
 Substatia Nigra
Produces dopamine, is
connected to the basal
ganglia – EPSE’s
 Amygdala
 mediates and controls
major affective mood
states such as friendship ,
love, affection, fear, rage
and aggression.
 Hippocampus
 Memory, particularly the
ability to turn short term
memory into long term
memory. Alzheimer's
disease.
 Meninges
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Dura mater
Arachnoid Mater
Subarachnoid space
Pia mater
 CSF
 2 main functions; shock
absorption and mediation of
blood's vessels and brain tissue in
exchange of nutrients.
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Circle of Willis
 carotid arteries and baliser arteries
 Blood Brain Barrier
 Protect the brain from chemicals
http://training.seer.cancer.gov/module_anatomy/unit5_3_n
erve_org1_cns.html
in the blood. Made up of tightly
packed endothelial
cells/capillaries making it difficult
to penetrate.
Resting Potential
 Resting potential
 Positive/negative charge
 Voltage
 Gated channels
 Sodium/ potassium
pump
 Action potential
 Threshold
 Depolarisation
Action Potential
 Calcium ion channels
stimulate the release of
neurotransmitters
 Vesicles fuse to the cell
membrane and release into
the synapse
 Lock and key effect
 Reuptake of
neurotransmitters into the
cell or broken down by
enzymes in the synaptic
cleft
 There are two kinds of neurotransmitters –
INHIBITORY and EXCITATORY.
 stimulate the brain
 calm the brain
 Neurotransmitter is a chemical
 Its released from the synaptic cleft
 Another term for neurotransmitter is a ligand
 Three main groups of neurotransmitters
 Amines
 Amino Acids
 Peptides
 Others
 Amines
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Dopamine
Noradrenaline
Adrenaline
Serotonin
 Amino Acids
 Glutamate and GABA
 Aspartate and glycine
 Peptides
 Cholecystrokinin
 Neuropetide Y
 Vasoactive intestinal
Peptide
 Substance P &
Substance K
 Somatosatin
 Others
 Acetylcholine
 Histamine
Small molecule neurotransmitters
Type
Neurotransmitter
Postsynaptic
effect
Other
Acetylcholine
Excitatory
Amino acids
Gamma aminobutyric
acid (GABA)
Inhibitory
Glycine
Inhibitory
Glutamate
Excitatory
Aspartate
Excitatory
Dopamine
Excitatory
Noradrenaline
Excitatory
Serotonin
Excitatory
Biogenic amines
Neural Communication
 Almost a million nerve
cells in the brain contain
dopamine.
 Role in
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complex movement
cognition
motor control
emotional responses such as
euphoria or pleasure.
 Newer antipsychotic
medication focus on
particular dopaminergic
pathways in the brain.
Lessening EPSE’s.
 The dopamine hypothesis
of psychosis – overactivity
of dopamine neurons in
the mesolimbic pathway of
the brain may mediate the
positive symptoms of
psychosis
 Mesolimbic pathway
responsible for pleasure,
effects of drugs and alcohol
and hallucinations and
delusions
 Five subtypes – D2 most important in terms of
psychosis
 Blockade of mesolimbic receptors leads to reduced
psychotic symptoms
 Blockade of the mesocortical pathway leads to
increased negative symptoms
 Dopamine and acetylcholine have a reciprocal
relationship Blockade of dopamine receptors increases the activity of
acetylcholine
 Over activity of acetylcholine causes EPSE
 Blockade of dopamine causes movement disorders in
the nigostriatal pathway
 Long term blockade causes “upregulation” and leads to
Tardive Dyskinesia
D2
Nigrostriatal pathway
extrapyramidal side
effects (EPS) and tardive
dyskinesia
Mesocortical
pathway
enhanced
negative and
cognitive
psychotic
symptoms
Tuberoinfundibular pathway
hyperprolactinemia (lactation, infertility,
sexual dysfunction)
Mesolimbic pathway
dramatic therapeutic
action on positive
psychotic symptoms
Type
Distribution
Postulated Roles
D1, 5-like
Brain, smooth
muscle
Stimulatory, role in
schizophrenia?
D2, 3, 4-like
Brain,
Inhibitory, role in
cardiovascular
schizophrenia?
system, presynaptic
nerve terminals
www.lundbeck.com.au
 Believed to be one of the great
influences on behaviour.
 Complex neurotransmitter.
 Surprisingly only 2% of
serotonin is found in CNS.
 Roles include
 Vasoconstriction,
gastrointestinal regulation.
 Low serotonin associated with
aggression, suicide, impulsive
eating, anxiety and low mood.
 Regulates general activity of
the CNS, particularly sleep.
 Delusions, hallucinations and
some of the negative
symptoms of schizophrenia.
www.rodensor.com/images/site_gra
phics/Dopamineseratonin
Type
Distribution
Postulated Roles
5-HT1
Brain, intestinal nerves Neuronal inhibition,
behavioural effects, cerebral
vasoconstriction
5-HT2
Brain, heart, lungs,
Neuronal excitation,
smooth muscle control, vasoconstriction, behavioural
GI system, blood
effects, depression, anxiety
vessels, platelets
5-HT3
Limbic system, ANS
Nausea, anxiety
5-HT4
CNS, smooth muscle
Neuronal excitation, GI
5-HT5, 6, 7
Brain
Not known
www.lundbeck.com.au
 Glutamate is found in all cells of the body
 control the opening of ion channels that allow calcium
to pass into nerve cells producing impulses
 Blocking of glutamate receptors produces psychotic
symptoms ( eg. By PCP) schizophrenic like symptoms
 Over exposure of neurons to glutamate cause cell
death seen in stroke and Huntington’s disease (PN).
 Inhibitory and its pathways are
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only found within the CNS.
control excitatory
neurotransmitters in the brain
and controlling spinal and
cerebral reflexes.
anxiety disorders
decreased GABA can lead to
seizure activity
Benzodiazepines and
barbiturates sedative
medication act on GABA
Benzo.org.au
 Found in the posterior
hypothalamus.
 Believed to be involved in
the regulation of the
sleeping and waking states.
 Histaminergic cells fire
rapidly during waking and
slowly during periods of
relaxation and tiredness.
Cease transmission during
REM and non-REM sleep
Type
H1
Histamine
Receptor
H2
histamine
receptor
H3 histamine
receptor
H4 histamine
receptor
Location
Found on smooth muscle,
endothelium, and CNS tissue
Located on parietal cells and
vascular smooth muscle cells
Function
bronchoconstriction, bronchial
smooth muscle contraction,
separation of endothelial cells
(responsible for hives), pain and
itching due to insect stings; receptors
involved in allergic rhinitis symptoms
motion sickness;
sleep regulation.
vasodilatation. stimulate gastric acid
secretion
Found on central nervous system Decreased neurotransmitter release:
and to a lesser extent peripheral
histamine, acetylcholine,
nervous system tissue
norepinephrine, serotonin
Found primarily in the basophils
and in the bone marrow. It is also
Plays a role in chemotaxis.
found on thymus, small intestine,
spleen, and colon.
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Cholinergic pathways
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thought to be involved in
cognition (esp. memory) and
our sleep/wake cycle
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parasympathetic nervous
system regulating bodily
functions such as heart rate,
digestion, secretion of saliva
and bladder function
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Alzheimer’s disease and
myathesia gravis (weakness of
skeletal muscles)
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Anti-cholinergic effects
Type
Distribution
M1
Nerves
M2
M3
M4
M5
NM
NN
Postulated Roles
CNS excitation, gastric acid
secretion
Heart, nerves, smooth muscle Cardiac inhibition, neural
inhibition
Glands, smooth muscle,
Smooth, muscle contraction,
endothelium
vasodilation
?CNS?
Not known
?CNS?
Not known
Skeletal muscles
Neuromuscular transmission
neuromuscular junction
Postganglionic cell body
dendrites
Ganglionic transmission
www.lundbeck.com.au
Norepinephrine (NE)
Found mainly in 3 areas of
the brain;
 the locus coeruleous,
 the pons
 reticular formation.
Main role;
Deprexchart.gif
Scienceblogs.com
 attention, alertness,
arousal
 sleep/wake cycle
 regulating mood
Type
Alpha1
Distribution
Brain, heart, smooth
muscle
Alpha2
Brain, pancreas, smooth Vasoconstriction,
muscle
presynaptic effect in GI
(relaxant)
Heart, brain
Heart rate (increase)
Beta1
Postulated Roles
Vasoconstriction, smooth
muscle control
Beta2
Lungs, brain, skeletal
muscle
Bronchial relaxation,
vasodilatation
Beta3
Postsynaptic effector
cells
Stimulation of effector
cells
www.lundbeck.com.au
The 3 Neurotransmitters song
Pharmacogenetics
 The variability in response to modern multi-target
drugs suggests a complex trait in which several genes
may play a part in the bodies response to drugs.
 Reported associations between polymorphic receptors
for metabolic enzymes and treatment response
confirm this hypothesis
 These results can be taken as evidence of the genomic
influence in drug response
 5-HTs, 5-HTT, H2 - Clozapine response prediction
 Arranz et al. (2000)
 5-HT6 - Clozapine response
 Yu et al. (1999)
 5-HTT - Response to SSRIs
 Smeraldi et al. (1998)
 Kim et al. (2000)
 APOE, PS1 and PS2 - Alzheimer’s disease treatment
response
 Cacabelos et al. (2000)
 CYP1A2 - Movement
disorders
 Basile et al. (2000)
D3 - Tardive dyskinesia
 Steen et al. (1997)
 Kapitany et al. (1998)
 CYP2D6 - Tardive dyskinesia
 Kapitany et al. (1998)
 Segman et al. (2000)
& Extra-pyramidal side-effects
 D4 - Clozapine response
 Scordo et al. (2000)
 CYP2C19 - Mephenytoin
blood levels
 Ferguson et al. (1998)
 D2 Short-term neuroleptic
response
 Malhotra et al. (1999)
 Schafer et al. (2001)
 D3 - Clozapine response
 Scharfetter et al. (1998)
 Ozdemir et al. (2001)
 Shaikh et al. (1993)
 5-HT2A - Clozapine
response
 Arranz et al. (1995, 1998b)
 5-HT2C - Clozapine
response
 Sodhi et al. (1995)
 Tardive dyskinesia
 Segman et al. (2000)
 The study of the movement of a drug through the body
 Absorption
 Distribution
 Metabolism
 Elimination
 Absorption
 The rate at which a drug gets out of the G.I tract and into
the blood stream
 Distribution
 Process of drug molecules leaving the blood stream to
reach tissues and organs
 General body capillaries
allow drug molecules to
pass freely into the
surrounding tissue.
 Brain capillaries have a dense walled structure & are
surrounded by glial cells (lipid). This prevents many drug
molecules from entering the surrounding tissue.
Glial cells
Capillary wall
 Metabolism: Detoxification
or breakdown. Enzymes
(Cytochrome P450) in liver
cells transform drug from
fat soluble to water soluble.
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 Elimination: removal of
drug from body. Most via
kidney’s, lungs & G.I. Tract
(small amounts)
nature.com
Pharmacokinetics clip
Drug receptor interaction: drug concentrated at the site of
action.
Effect (body responses): Therapeutic effects, intoxication &
side effects.
The effect will vary depending on age, gender & health of
person, plus the route, frequency of use, duration of use
and the environment in which the drug is consumed.
 Blockade of receptors
 Receptor sensitivity
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changes
Reuptake inhibition
Interference with storage
vesicles
Pre-curser chain
interference
Synaptic enzyme inhibition
Second messenger cascade
Neurotransmitter
Re-uptake pump
Receptor
Axon
Dendrite
Synapse
Presynaptic storage vesicles
Acetylcholine
GABA
Serotonin
Dopamine
Glutamate
Noradrenaline
Fine muscle movement, decision
making, stimulates the hypothalamus
to release hormones
Stimulates the ANS – Fright & Flight
Dopamine
Noradrenaline
=
Serotonin
sleep regulation, hunger, mood states, pain
perception, aggression and sexual behaviour
Acetylcholine
Learning & Memory
Acetylcholine
Noradrenaline
& Serotonin
Glutamate,
Noradrenaline
Dopamine
Acetylcholine
Dopamine
Acetylcholine
Acetylcholine
Dopamine
Dopamine
Norepinephrine
Acetylcholine
Serotonin
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