Carl Sagan Lobes of the brain forebrain Midbrain Hindbrain Protection and Blood Supply Structure and Functions of a Neuron Synaptic Transmission Neurotransmitters Overview Central Nervous System ID: 488806
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Slide1
Brain Structure & FunctionSlide2
Carl SaganSlide3
Lobes of the brain (forebrain)Midbrain/ HindbrainProtection and Blood Supply
Structure and Functions of a Neuron
Synaptic Transmission
Neurotransmitters
OverviewSlide4
Central Nervous System
The central nervous system consists of the brain and the spinal cord and is responsible for our basic functions, personality and behaviour.Slide5
Cerebrum and Cerebral cortexLeft and Right HemispheresLeft 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
ForebrainSlide6
The Brain
Most complex organ in the body
Weighs 1,300 grams
Contains billions of neural networks that interact to create human behaviourSlide7
The Lobes of the Brain
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
Occipital Lobe
Barlow and Durand 2005Slide8
Located at the front of both cerebral hemispheres
Primary motor cortex
Pre-motor cortex
Broca’s
Area- Motor Production of speech
Complex Functioning
Personality
judgement
Insight
Reasoning
problem solving,
abstract thinking
working memory
Frontal LobeSlide9
Parietal Lobe
Located behind the temporal lobe
Sensory information
Temperature
Pain
Texture
Spatial orientation
Perception
Recognising object by touch
Links visual and sensory information together
NeglectSlide10
Auditory information
Higher order visual information
Complex memory
Memory of faces
Comprehension of language
(
Wernicke’s area)
Temporal LobeSlide11
http://www.nidcd.nih.gov/health/voice/aphasia.asp)Slide12
Occipital Lobes
Rearmost portion of the brain
Visual processing area
Corpus Callosum- Fibre bundle in the brain that connects the two hemispheres together. Slide13
Other Important Structures
Hypothalamus
Thalamus
Cerebellum
Pons
Medulla Oblongata
Reticular formation
Basal Ganglia
Substantia Nigra
Amygdala
HippocampusSlide14
Diencephalon
Thalamus
filters sensory information, controls mood states and body movement associated with emotive states
Hypothalamus
Central control’ for pituitary gland. Regulates autonomic, emotional, endocrine and somatic function. Has a direct involvement in stress and mood states.
(http://training.seer.cancer.gov/module_anatomy/unit5_3_nerve_org1_cns.html)Slide15
Cerebellum regulates equilibrium, muscle tone, postural control, fine movement and coordination of voluntary muscle movement.
Pons
Relay station between cerebrum and cerebellum
Hindbrain
www.deryckthake.com/psychimages/hindbrain.Slide16
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. Slide17
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’sSlide18
Limbic System
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.Slide19
Pituitary and Pineal GlandsSlide20
Protection and Blood Supply
Meninges
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.
Circle of Willis
carotid arteries and
baliser
arteries
Blood Brain Barrier
Protect the brain from chemicals in the blood. Made up of tightly packed endothelial cells/capillaries making it difficult to penetrate.
http://training.seer.cancer.gov/module_anatomy/unit5_3_nerve_org1_cns.htmlSlide21
NeuronsSlide22
Structure of a NeuronSlide23
Resting
PotentialSlide24
Function of a Neuron
Resting potential
Positive/negative charge
Voltage
Gated channels
Sodium/ potassium pump
Action potential
Threshold
DepolarisationSlide25
Action PotentialSlide26
Action PotentialSlide27
Synaptic Transmission
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 cleftSlide28Slide29
NeurotransmittersSlide30Slide31
There are two kinds of neurotransmitters – INHIBITORY
and
EXCITATORY
.
stimulate the braincalm the brain Slide32
Neurotransmitter is a chemicalIts released from the synaptic cleft
Another term for neurotransmitter is a ligand
Three main groups of neurotransmitters
Amines
Amino AcidsPeptides
Others
Neurotransmitters Slide33
Amines
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
HistamineSlide34
Neurotransmitters
Small molecule neurotransmitters
Type
Neurotransmitter
Postsynaptic effect
Other
Acetylcholine
Excitatory
Amino acids
Gamma
aminobutyric
acid (GABA)
Inhibitory
Glycine
Inhibitory
Glutamate
Excitatory
Aspartate
Excitatory
Biogenic amines
Dopamine
Excitatory
Noradrenaline
Excitatory
Serotonin
ExcitatorySlide35
Neural CommunicationSlide36
AMINESSlide37
Dopamine (DA)
Almost a million nerve cells in the brain contain dopamine.
Role in
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. Slide38
Dopamine Theory
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 delusionsSlide39
Five subtypes – D2 most important in terms of psychosisBlockade of mesolimbic receptors leads to reduced psychotic symptoms
Blockade of the mesocortical pathway leads to increased negative symptoms
Dopamine ReceptorsSlide40
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
Dopamine Receptors Slide41
Tuberoinfundibular
pathway
hyperprolactinemia
(lactation, infertility, sexual dysfunction)
D2
ANTAGONIST
Nigrostriatal
pathway
extrapyramidal
side effects (EPS) and
tardive
dyskinesia
Mesocortical
pathway
enhanced negative and cognitive psychotic symptoms
Mesolimbic pathway
dramatic therapeutic action on positive psychotic symptomsSlide42
Type
Distribution
Postulated Roles
D1, 5-like
Brain, smooth muscle
Stimulatory, role in schizophrenia?
D2, 3, 4-like
Brain, cardiovascular system,
presynaptic
nerve terminals
Inhibitory, role in
schizophrenia?
Dopamine Receptors
www.lundbeck.com.auSlide43Slide44
Serotonin (5ht)
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_graphics/DopamineseratoninSlide45
Serotonin Receptors
Type
Distribution
Postulated Roles
5-HT1
Brain,
intestinal
nerves
Neuronal inhibition, behavioural effects, cerebral vasoconstriction
5-HT2
Brain, heart, lungs, smooth muscle control, GI system, blood vessels, platelets
Neuronal excitation, vasoconstriction, behavioural effects, depression, anxiety
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.auSlide46Slide47
Amino AcidsSlide48
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).
GlutamateSlide49
GABA Gamma-aminobutyric
acid
Inhibitory and its pathways are 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.auSlide50Slide51
OthersSlide52
Histamine
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 sleepSlide53
Type
Location
Function
H1
Histamine Receptor
Found
on
smooth
muscle, endothelium, and CNS tissue
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.H2histamine receptor
Located on parietal cells and vascular smooth muscle cells
vasodilatation
.
stimulate
gastric
acid
secretion
H
3
histamine
receptor
Found on central nervous system and to a lesser extent peripheral nervous system tissue
Decreased neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin
H
4
histamine receptor
Found primarily in the basophils and in the
bone
marrow
. It is also found on thymus,
small
intestine, spleen, and colon.
Plays a role in
chemotaxis
.Slide54
Acetylcholine (ACh)
Cholinergic pathways
thought to be involved in cognition (esp. memory) and our sleep/wake cycle
parasympathetic nervous system regulating bodily functions such as heart rate, digestion, secretion of saliva and bladder function
Alzheimer’s disease and
myathesia
gravis (weakness of skeletal muscles)
Anti-cholinergic effects Slide55
Acetylcholine Receptors
Type
Distribution
Postulated Roles
M1
Nerves
CNS excitation, gastric acid secretion
M2
Heart, nerves, smooth muscle
Cardiac inhibition, neural inhibition
M3
Glands, smooth muscle, endothelium
Smooth, muscle contraction, vasodilation
M4
?CNS?
Not known
M5
?CNS?
Not known
NM
Skeletal muscles neuromuscular junction
Neuromuscular transmission
NN
Postganglionic cell body dendrites
Ganglionic transmission
www.lundbeck.com.auSlide56
Noradrenaline
Norepinephrine
(NE)
Found mainly in 3 areas of the brain;
the locus
coeruleous
,
the pons
reticular formation.
Main role;
attention, alertness
, arousal
sleep/wake cycle
regulating
mood
Deprexchart.gif
Scienceblogs.comSlide57
Noradrenaline Receptors
Type
Distribution
Postulated Roles
Alpha1
Brain, heart, smooth muscle
Vasoconstriction, smooth muscle control
Alpha2
Brain, pancreas, smooth muscle
Vasoconstriction, presynaptic effect in GI (relaxant)
Beta1
Heart, brain
Heart rate (increase)
Beta2
Lungs, brain, skeletal muscle
Bronchial relaxation, vasodilatation
Beta3
Postsynaptic effector cells
Stimulation of effector cells
www.lundbeck.com.auSlide58
The 3 Neurotransmitters songSlide59Slide60
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 responseSlide61
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)
Polymorphisms in genes associated with metabolic enzymes & neurotransmitters Slide62
CYP1A2 - Movement disorders Basile et al. (2000)
CYP2D6 - Tardive dyskinesia
Kapitany et al. (1998)
& Extra-pyramidal side-effects
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)
D3 - Tardive dyskinesia
Steen et al. (1997)
Kapitany et al. (1998)
Segman et al. (2000)
Ozdemir et al. (2001)
D4 - Clozapine response
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)Slide63
PharmacogenomicsSlide64
PharmacokineticsSlide65
The study of the movement of a drug through the bodyAbsorption
Distribution
Metabolism
Elimination
PharmacokineticsSlide66
AbsorptionThe 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
PharmacokineticsSlide67
Body membranes affecting drug distribution: Capillaries
General
body capillaries allow drug molecules to pass freely into the surrounding tissue.Slide68
Brain capillaries have a dense walled structure & are surrounded by glial cells (lipid). This prevents many drug molecules from entering the surrounding tissue.
Blood Brain Barrier BBB
Glial cells
Capillary wallSlide69
Termination of drug action.
Metabolism: Detoxification or breakdown. Enzymes (Cytochrome P450) in liver cells transform drug from fat soluble to water soluble.
Elimination: removal of drug from body. Most via kidney’s, lungs & G.I. Tract (small amounts)
nature.comSlide70
Pharmacokinetics clipSlide71
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.
Pharmacodynamics.
How drugs act on bodySlide72
Mechanism of action
Blockade of receptors
Receptor sensitivity changes
Reuptake inhibition
Interference with storage vesicles
Pre-curser chain interference
Synaptic enzyme inhibition
Second messenger cascade Slide73
Receptor
Neurotransmitter
Synapse
Presynaptic storage vesicles
Re-uptake pump
Dendrite
AxonSlide74
Agonist = MimicSlide75
Agonist = Facilitate bindingSlide76
Blocking = Antagonist Slide77
Up-regulationSlide78
Down-regulationSlide79
Acetylcholine
Serotonin
Dopamine
Noradrenaline
Glutamate
GABASlide80
Normal
Acetylcholine
Dopamine
Noradrenaline
Serotonin
=
Stimulates the ANS – Fright & Flight
Fine muscle movement, decision making, stimulates the hypothalamus to release hormones
Learning & Memory
sleep regulation, hunger, mood states, pain perception, aggression and sexual behaviourSlide81
Depression
Noradrenaline& Serotonin
AcetylcholineSlide82
Mania
Acetylcholine
Glutamate, Noradrenaline DopamineSlide83
Schizophrenia
Acetylcholine
DopamineSlide84
Parkinsons
Dopamine
AcetylcholineSlide85
Dementia
Acetylcholine
Dopamine
Norepinephrine
SerotoninSlide86
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