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Brain Structure & Function
Carl Sagan
Lobes of the brain (forebrain)Midbrain/ HindbrainProtection and Blood SupplyStructure and Functions of a NeuronSynaptic TransmissionNeurotransmitters
Overview
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.
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
Forebrain
The Brain
Most complex organ in the body
Weighs 1,300 gramsContains billions of
neural networks that interact to create human behaviour
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 themFrontal LobeTemporal LobeParietal LobeOccipital Lobe
Barlow and Durand 2005
Located at the front of both cerebral hemispheres Primary motor cortexPre-motor cortexBroca’s Area- Motor Production of speechComplex FunctioningPersonality
judgementInsightReasoningproblem solving, abstract thinking working memory
Frontal Lobe
Parietal LobeLocated behind the temporal lobeSensory information
TemperaturePainTexture
Spatial orientation Perception Recognising object by touchLinks visual and sensory information
togetherNeglect
Auditory informationHigher order visual informationComplex memory
Memory of facesComprehension of language (Wernicke’s area)
Temporal Lobe
http://www.nidcd.nih.gov/health/voice/aphasia.asp)
Occipital LobesRearmost portion of the brainVisual processing area
Corpus Callosum- Fibre bundle in the brain that connects the two hemispheres together.
Other Important StructuresHypothalamusThalamusCerebellumPonsMedulla OblongataReticular formationBasal GangliaSubstantia NigraAmygdalaHippocampus
DiencephalonThalamus
filters sensory information, controls mood states and body movement associated with emotive states
HypothalamusCentral 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)
Cerebellum regulates equilibrium, muscle tone, postural
control, fine movement and coordination of voluntary muscle movement.
PonsRelay station between cerebrum and
cerebellum
Hindbrain
www.deryckthake.com/psychimages/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 GangliaControl of muscle
tone, activity, posture, large muscle movements and inhibit unwanted muscle movements.
Substatia NigraProduces dopamine, is
connected to the basal ganglia – EPSE’s
Limbic SystemAmygdala
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.
Pituitary and Pineal Glands
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.html
Neurons
Structure of a Neuron
Resting Potential
Function of a NeuronResting potentialPositive/negative
chargeVoltageGated channelsSodium/ potassium
pumpAction potential
ThresholdDepolarisation
Action Potential
Action Potential
Synaptic TransmissionCalcium ion channels
stimulate the release of neurotransmitters
Vesicles fuse to the cell membrane and release into the synapse
Lock and key effectReuptake of
neurotransmitters into the cell or broken down by enzymes in the synaptic cleft
Neurotransmitters
There are two kinds of neurotransmitters – INHIBITORY and EXCITATORY.
stimulate the braincalm the brain
Neurotransmitter is a chemicalIts released from the synaptic cleftAnother term for neurotransmitter is a ligandThree main groups of neurotransmitters
AminesAmino AcidsPeptidesOthers
Neurotransmitters
AminesDopamineNoradrenalineAdrenalineSerotonin
Amino AcidsGlutamate and GABAAspartate and glycine
PeptidesCholecystrokininNeuropetide YVasoactive intestinal
PeptideSubstance P &
Substance KSomatosatin
OthersAcetylcholineHistamine
NeurotransmittersSmall 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 Excitatory
Neural Communication
AMINES
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.
Dopamine TheoryThe 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 Receptors
Dopamine and acetylcholine have a reciprocal relationship-Blockade of dopamine receptors increases the
activity of acetylcholineOver activity of acetylcholine causes EPSEBlockade of dopamine causes movement
disorders in the nigostriatal pathwayLong term blockade causes “upregulation” and
leads to Tardive Dyskinesia
Dopamine Receptors
Tuberoinfundibular pathway hyperprolactinemia
(lactation, infertility, sexual dysfunction)
D2ANTAGONIST
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 symptoms
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.au
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/Dopamineseratonin
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 knownwww.lundbeck.com.au
Amino Acids
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).
Glutamate
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.au
Others
HistamineFound 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 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.
H2
histamine receptor
Located on parietal cells and vascular smooth muscle cells
vasodilatation. stimulate gastric acid secretion
H3 histamine receptor
Found on central nervous system and to a lesser extent peripheral nervous system tissue
Decreased neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin
H4 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.
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
Acetylcholine ReceptorsType 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 knownM5 ?CNS? Not knownNM Skeletal muscles
neuromuscular junctionNeuromuscular transmission
NN Postganglionic cell body dendrites
Ganglionic transmission
www.lundbeck.com.au
NoradrenalineNorepinephrine (NE)
Found mainly in 3 areas of the brain; the locus coeruleous, the pons reticular formation.
Main role;attention, alertness,
arousalsleep/wake cycle regulating mood
Deprexchart.gif
Scienceblogs.com
Noradrenaline ReceptorsType Distribution Postulated RolesAlpha1 Brain, heart, smooth
muscleVasoconstriction, 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.au
The 3 Neurotransmitters song
PharmacogeneticsThe 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)
Polymorphisms in genes associated with metabolic enzymes & neurotransmitters
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)
Pharmacogenomics
Pharmacokinetics
The study of the movement of a drug through the bodyAbsorptionDistribution MetabolismElimination
Pharmacokinetics
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
Pharmacokinetics
Body membranes affecting drug distribution: Capillaries
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.
Blood Brain Barrier BBB
Glial cells
Capillary wall
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.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.
Pharmacodynamics. How drugs act on body
Mechanism of actionBlockade of receptorsReceptor sensitivity
changesReuptake inhibitionInterference with
storage vesiclesPre-curser chain
interferenceSynaptic enzyme
inhibitionSecond messenger
cascade
Receptor
Neurotransmitter
Synapse
Presynaptic storage vesicles
Re-uptake pump
DendriteAxon
Agonist = Mimic
Agonist = Facilitate binding
Blocking = Antagonist
Up-regulation
Down-regulation
Acetylcholine
Serotonin
Dopamine
Noradrenaline
Glutamate
GABA
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 behaviour
Depression
Noradrenaline& Serotonin
Acetylcholine
Mania
Acetylcholine
Glutamate, Noradrenaline Dopamine
Schizophrenia
AcetylcholineDopamine
Parkinsons
DopamineAcetylcholine
Dementia
Acetylcholine
Dopamine
Norepinephrine
Serotonin
Boyd (2002). Psychiatric Nursing , contemporary practice .Lippincott, USA
Rosenweig, Breedlove and Leiman (2002) Biological Psychology: an introduction to cognitive, behavioural and clinical neuroscience 3rd Edition.Sineur Associates , Inc USA.
Stuart and Laraia (2005) Prinicples and Practice of Psychiatric Nursing. Mosby, USA.
Barlow and Durand (2005). Abnormal Psychology, and intergrated approach.Thompson/Wadsworth, Australia.
Leonard BE (1997). Fundamentals in Psychopharmacology. 2nd ed. Chichester: Wiley & Sons.
Purves DE, Augustine GJ, Fitzpatrick D, et al. (eds). Neuroscience. Sunderland, MA: Sinauer Associates, Inc; 1997.
Lundbeck Institute, www.brainexplorer.com Blakemore & Frith (2005). The Learning Brain. Blackwell Publishing Begley (2005). The blood brain Barrier. Gauchers News May 2005c Staddon S, Arranz MJ, Mancama D, Mata I, Kerwin RW
(2002) Clinical applications of pharmacogenetics in psychiatry, Psychopharmacology 162: 18–23
References
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