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