Neurophysiology

Cell Membrane

*Bilayer of lipid plus cholesterol molecules plus proteins in the form of ion channels, NT receptors and ion pump

*Intracellular is negatively charged

*Extracellular is less negatively charged

*The charge gradient is maintained through the cell membrane by controlling ion channels

*Potassium is highly concentrated intracellular and sodium is extracellular

Ion channels

*Each channel is a glycoprotein molecule which has a pore that can be opened and closed

*Ion channels are specific for certain ions

*Ion channels are closed during rest

*Ion channels opened in response to:

1-Ligand gated ion channels (binding of a sub to a receptor on cell membrane)

2-Voltage gated ion channels (changes in membrane potential)

Ligand gated channels

1-Excitatory neurotransmitters

Open cation channels and depolarize cell membrane and may lead to action potential (excitatory postsynaptic potential)

2-Inhibitory neurotransmitter

Open chloride channels that hyperpolarize the cell membrane and decrease action potential (inhibitory postsynaptic potential)

Three types of ligand gated channels

A-Direct coupled (NT acts directly on the channel)

B-G-protein coupled (NT→NT receptor→ Activates G protein →Activates ion channels)

C-2^nd messenger coupled (NT→ 2nd messenger →ion channels)

Action potential

*Resting membrane potential is 70-80mV (polarization)

*With a stimulus the following occur:

-The ligand gated ion channels opened

-Sodium ions enter the cells

-The inner surface of the membrane became less negatively charged

-If the potential reaches 55mV (spike threshold)

-Voltage gated ion channels are opened so

-High flow of sodium to the inside occurred

-Action potential is generated which is a brief (0.1-2msec) wave of reversed membrane potential that moves along the axis.

-During action potential the interior of the cell is positively charged. then

-The second ion channels to be opened in action potential is calcium channels so calcium flow to the inside (the inside became more positively charged)

*Calcium not only helps the membrane potential but also 1-Works as 2^nd messenger so initiate protein protein interactions and gene regulation

2-Responsible for the release of NT molecules

3-Activate ion channels of potassium so help to arrest action potential (depolarized state) and produces afterhyperpolarization (the cell became more negatively charged than at baseline = refractory period).

*The rate of speed of action potential determines the conduction velocity along the axon and the nerves.

*Bared axon conduct at a rate of 1meter per sec

*Myelinated axons conduct at a higher rate

*Fast rate of conduction is needed in rapid processing of information

*Myelin is segmented each segment is separated from other by gap called Node of Ranvier

*Because the myelin is acting as insulator the impulse transmitted along the axis jump from one node of Ranvier to another so the rate of conduction increased very much and may reach to 65 meter per sec

Translation of Action Potential Into Chemical Neurotransmitter

As the action potential reaches the synaptic terminal it activates voltage gated calcium channel → calcium flow to the inside →Protein protein and protein lipid interactions →vesicles became attached to synaptic membrane →evacuate the NT (exocytosis)

If in a muscle the calcium flows →movement of myosin on actin fibers (excitation contraction coupling)

Synapses

1-Axosomatic (the axon of presynaptic and the cell body of post synaptic)

2-Axoaxonic

3-Axodendritic

Synapse also may be

A-Chemical synapses

B-Electrical synapses (gap junction) allow direct flow of ions from the axon to the other cell

C-Conjoint synapses (mixed)

*Development of synapses is a dynamic process along the age

*The mechanical adhesive property of synapse is due to adhesive molecule called  calcium dependant cadherin

*Trophic substances called growth factors mediate the dynamic remodeling process of synapses through certain specific receptors.

*NMDA receptors are important for synaptic remodeling and long-term potentiation LTP(strengthening of certain synapses).

*LTP is important for memory.

Synthesis of neurotransmitters

*All NT synthesized in the presynaptic terminal except peptide NT which synthesized in the cell body

*Synthesis is stimulated by

1-Influx of calcium

2-cAMP

3-Change in level of circulating hormone

* synaptic vesicle may contain a mixture of peptide and amine NT. And different vesicles may contain different NT.

Vesicles

*2 substance called synapsin and Rab3 control localization of vesicles.

*Synaptogmin and synaptobrevin in vesicle membrane and neurexins and syntaxins in axon membrane control the fusion of the vesicle to the presynaptic membrane

*synaptophysin aids in the creation of a pore in the presynaptic membrane.

 

Presynaptic transmembrane transporter

It is a molecule that returns free monoamine NT to the nerve terminals to be repackaged into vesicles or degraded by MAO

Drugs that inhibit  PSTT are

TCAs

MAOIs

SSRIs

Cocaine

*it was found that certain serotonin transporter is increased in patients have anxiety or neuroticism. (i.e. serotonin uptake is much so free serotonin is decreased ).

*But SSRIs as prozac don’t improve anxiety.

MAO

There is two types of MAO

MAO-A for 5HT and NE

MAO-B for DA

Post synaptic receptors

*Its function is to alter the postsynaptic membrane potential either increase (action potential) or decrease (hyperpolarization) according to the type of NT.

*Single molecule of NT lead to change of only 1mV so to change resting mem potential from –70 or 80 to –55 we need many molecules from the NT

*Supersensitivity is greater than usual response to a constant amount of the NT

*Subsensitivity is lower than usual response to a constant amount of the NT.

The sensitivity of the receptors is related to:

1-Number

2-Affinity to NT

3-Efficiency (how much the binding to it is translated into intraneuronal message).

Hormones

Circulating steroids and thyroid hormones diffuse through the synaptic membrane to the inside of the cell then bind to cytoplasmic receptor which transfer them to the nucleus where they regulate gene expression.

G Proetein

Formed of Alpha , beta , gama subunits and Guanosine diphosphate or triphostphate attached to the alpha subunit .

G protein binds to a receptor

↓

Receptor acquire high affinity to NT

↓

NT binds to the receptor

↓

GDP→GTP

↓

Dissociation of the complex

↓

NT—Receptor— Alpha GTP—Beta gama subunits

Alpha GTP

↓

Stimulate or inhibit effector molecules

(Ion channels or adenylecyclase)

Then

 

Alpha subunit

↓

GTP→GDP

So alpha GDP rejoin beta gamma subunits

Alpha subunits are three types

1-Alpha stimulatory for adenyle cyclase

2-Alpha inhibitory for adenyle cyclase

3-alpha stimulatory for phophoinositol 2^nd messenger

 

α

Second Messengers

First messenger is the NT

2^nd messengers are :

1-cAMP

2-cGMP

3-Calcium

4-Phosphoinositol metabolites

Inositol diphosphate IP3

Diacyleglycerol DAG

5-Eicosanoid metabolites

6-Gases as No and CO

Calcium

2 sources of calcium

A-calcium enter the cells from voltage gated or ligand gated channels

B-intraneuronal vesicles under effect of IP3

Actions of Calcium

1-2^nd messenger

2-with calcium binding proetins as calmodulin

3-stimulate formation of NO

4-excitotoxic cellualr damage

*Calcium may be concentrated in a localized dendrites or area so lead to local changes in synaptic efficiency and so may act as a basis for memory and learning.

Phosphoinositol metabolites

*Ip3 causes release of calcium from intraneuronal vesicles

*DAG stimulate specific protein kinases.

Gases

1-NO

*Has the ability to relax vascular smooth muscles so it may mediate local increases in the cerebral blood flow.

*Stimulation of guanyle cyclase

2-CO

*Stimulation of guanyle cyclase.

Eicosanoids

Phospholipasae A2

↓

Phospholipid of the cell membrane →Free arachidonic acid

Free arachidonic acid

↓

prostaglandins, cyclic endoperoxides and leukotrienes

These compounds act as 2^nd messenger

JAK-STAT

*JAK is a receptor for cytokines called Janus Kinase

*It phosphorylates a family of trnscription factors called STAT.

*This family is translocated directly to the nucleus and resulted in regulation of gene of expression.

*JAK-STAT system mediates trophic signals that support neuronal survival

*Each of the 2^nd messengers resulted in activation of protein kinase by phosphorylation

*There are 4 types of protein kinases

1-cAMP dependent protein kinase

2-cGMP dependent protein kinase

3-Calcium /calmodulin dependant protein kinase

4-Calcium phosphatidylserine protein kinase

 

*Protein kinases are deactivated by protein phophatases

*The process of phophphorylation and dephosphorylation works as on-off switch for function of the protein.

Lithium works by decreasing activity of Calcium phosphatidylserine protein kinase PKC.

 

Neurotransmitters

For the substance to be a NT it must

1-synthesized in the neuron

2-present in presynaptic neuron and released by depolarization in adequate amount.

3-if taken exogenously works mimic the endogenous one

4-there is a mechanism to remove or deactivate it in the synaptic cleft

NT	Neuromodulator	Neurohormone
Immediate effect	Long term effect	Released in the blood stream then to the extraneuronal  space
Short lived effect	Long lived effect
Just elicit action potential	Fine tuning for the effects

 

Classification

1-Biogenic amines	2-Amino acids	3-Peptides
Small % of neurons	70% of neurons	Intermediate %
6 types	2 confirmed types	200-300 type
Epi-norEpi-DA-5HT-A.ch-Histamine	Glutamate ++ GABA—
There are a lot of drugs acting on them	Drugs acting are toxic even in small doses	Few drugs working on their receptors  as opiates

4-Nucleotides

5-Gases

6-Eicosanoids

7-Anandamides

8-Sigma receptors

Biogenic amines

DA-Epi-Nor Epi are synthesized in the axon terminal from tyrosine

Serotonin is synthesized from tryptophane

All biogenic amines aresynthesized  in the axon terminal.

Synthetic enzymes are formed in the cell bodies then transported to the axon terminal.

Amino acids

*Simply all brain function depend on balance between these two NT as glutamate is stimulatory and GABA is inhibitory.

*All other NT works to maintain this balance.

*Glutamate works on NMDA receptors which have a role in learning, memory, anxiety disorders and schizophrenic disorders

Peptide NT

Short chain of amino acids formed in the cell bodies as preprohormones.

Transformed along the axis to the synaptic terminal and during their transportation changed to prohormone then hormone.

Their transportation and modification to hormone form take long time

Can not recycled after their effect.

 

Nucleotides

*P1 receptors have high affinity to adenosine

–2 types of P1 which are A1 and A2

*Both of A1 and A2 works through G protein

*Binding of adenosine to A1 produces effects opposite to binding of it to A2

–P2 receptors have high affinity to ATP

–ATP itself works as NT on P2 receptors and is stored in synaptic vesicles is responsible for opening of sodium , potassium and calcium channels.

Gases

NO

Acts as intraneuronal 2^nd messenger and as NT

Lead to relaxation of vascular smooth muscles

Activate cGMP

 

Activation of NMDA by glutamate or agonists→calcium enter the neuron→ activation of NO synthsae→ NO

NO

↓

cGMP

which lead to entry of large amount of calcium

*No can be diffused to other neurons

*So glutamate may lead to large amount of calcium flow

*NO metabolized into toxic free radicals which together with calcium may lead to cell death (excitotoxicity)

*Inhibitor of NOS may be beneficial in preventing tissue damage after strokes

*No is involved in memory and learning

Co

It also stimulates guanyle cyclase

Eicosanoids  (Prostanoids)

*There are 8 receptors

Thromboxan A2 R prostacyclin R-

Prostaglandin F Prostaglandin D R

4 subtypes of prostaglandin E R

*Also there are leukotreines binding sites

Anandamides

*They are a ligands for cannabinoid receptors

*There are 2 types of cannabinoid R

CB1 central

CB2 peripheral

*They displays similar but less potent effect than tetrahydrocannbinol as decrease of IOP, decrease activity, and decrease of pain

Sigma Receptors

*The endogenous ligand of this receptor is not been identified up till now

*Exogenously it binds to haloperidol and pentazocin (talwin).

Amino Acids NT

Stimulatory EAAs

All are dicarboxylic

Glutamate Aspartate

N-Acetyleaspartylglutamate (NAAG) Cysteate

Homocysteate

Inhibitory IAAs

All are monocarboxylic

GABA Glycine

Taurine Beta alanin

 

Glutamate

Site of synthesis Presynaptic neuron terminal

Storage Synaptic vesicles

Synthesis Enzyme

Metabolism by reuptake

Release is stimulated by Nicotine

Receptors   are 5

1-NMDA-R

2-5- Non NMDA-R

*NMDA R opens only when binds to 2 glutamate molecules and one glycine molecule

* Glutamate initially depolarizes Non NMDA receptors to a level of –65mV then NMDA-R activated.

*Magnesium and PCP block NMDA.

NMDA played a role in memory and learning because

Opening of the NMDA to calcium influx (activation) needs a prolonged set of temporally coordinated stimuli →Cascade of intracellular events→ expression of certain gene → stabilize and reinforce the synapses → maintaining activation of the receptor.

NMDA antagonists block memory formation.

Glutamate and Psychopathology

*It plays an important role in

1-Excitotoxicity

Stimulation of glutamate receptors →excessive intraneuronal calcium and NO → activate proteases →destruction of neuronal integrity (during acute strokes).

2-Schizophrenia

Reduction of NMDA activity  →psychotic symptoms.

*So too much glutamate activity →excitotoxicity   and

*Too little glutamate activity → psychosis.

*DA and glutamate have opposing effects.

GABA

*Synthesized from glutamate by glutamic acid decarboxylase GAD and potentiated by pyridoxine vitamin B6.

*Metabolized by GABA transaminase

*Does not cross the BBB so not present outside CNS

Receptors are 3

*GABA-A and GABA-B directly acting ligand gated chloride ion channels

*GABA-C G protein related

*GABA-A has binding sites for BDZ, barbiturates and GABA.

*Baclopfen is GABA-B agonist treat spasticity

*Picrotoxin is GABA-A antagonist lead to seizures

Psychopathology

*GABA is related to pathophysiology of anxiety disorders and epilepsy.

 *Drugs that act to enhance GABA activity as tegretol and depakine  are used to treat bipolar-I disorder.

Glycine

*It has two receptors

1-Binding sites on NMDA to initiate glutamate activity  (non-strychnine sensitive glycine receptor).

2-Strychnine sensitive glycine receptors which is inhibitory.

*There are trials to treat schizophrenia especially negative symptoms by glycine and its agonists as they enhance glutamate activity.

Biogenic Amines

**They are less abundant than AA NT but they project widely to different areas of the brain.

**All current drugs for psychosis, mood, and anxiety disorders are depending on them

Dopamine

Tyrosine 1→ DOPA 2→ DOPAmine 3→ Nor Epi

Nor Epi 4→Epi

1-tyrosine hydroxylase

2-Aromatic aminoa acid decarboxylase

3-Dopamine beta hydroxylase

4-Phenyleethanolamine N- methyletransferase

Dietary changes of tyrosine did not affect catecholamines

After synthesis of DA , specific transporter takes it to the synaptic vesicles.

Metabolism by 2 mechanisms

A-Reuptake into the presynaptic terminal and to the vesicles

B-Degraded by two enzymes

MAO-B in outer surface of presynaptic mitochondria

COMT in cytoplasm of post synaptic neuron

*The end product of DA is HVA

Dopaminergic tracts

1-The mesolimbic system mainly D2

-From ventral tegmental area to whole cerebral cortex and limbic system

-Responsible for antipsychotic action of APD

• The nigrostriatal system mainly D2

*From substantia nigra to corpus striatum

A-Responsible for Extrapyramidal effects with conventional APD

B-Degenerated in Parkinson’s disease

C-Related to control of mood so depression is common in Parkinson’s D

D-Increased DA activity at caudate may be responsible for tic disorder esp Tourette’s syndrome.

• Infundibular system mainly

From the arcuate nucleous and periventricular area of the hypothalamus to the infandibulum of anterior pitutary

*DA at this tract works as release inhibiting factor for prolactin level

*So prolactin level increased three folds with typical APD

DA receptors

5 subtypes arranged into 2 families , D1 and D5 family and D2-3-4 family

*D1 and D5→Gs protein →formation of cAMP

D1 has lesser affinity for DA than D5

*D2  →Gi protein  → decreased formation of cAMP.

 

D2	D3	D4
BG	Nucleus accumbens	Frontal coretx

Increased putaminal D2 receptors was associated with less negative symptoms

Decreased putaminal D2 receptors was associated with negative symptoms (conventional APD)

 

DA and Drugs

*Long term block of DA receptors by APD lead to upregulation (increased no) →Tardive dyskinesia

*Amphetamine causes release of DA. Cocaine causes block of up take of DA

Use of these two substances may deplete brain stores of DA

DA is involved in the brain reward system

Deletion of DA transporter in mice block effect of cocaine

*Nicotine stimulate release of DA and glutamate so smokers have decreased risk of Parkinson’s D and Alzheimer’s D

Nicotine analogues are under trials to ttt Parkinson

Nicotine transdermal patch is under trials to correct cognitive impairment of haloperidol

*Bupropion and cogentin block DA transporter

*MPTP leads to degeneration of DA neurons in nigrostriatum

*Serpasil lead to irreversible depletion of DA vesicles while tetrabenzene is reversible

DA and psychopathology

1-DA hypothesis of Schizophrenia  ( see before)

2- DA activity is increased in mania and decreased in depression

 

Nor Epinephrine and Epinephrine

NE is more abundant in the brain than in serum while epinephrine is the opposite.

Adrenegric tracts

From the Locus Ceruleus of pons to cortex , thalamus, hypothalamus and limibic system.

Metabolism as DA but MAO-A

Adrenergic receptors

Alpha-1 (1a-1b-1c-1d)   phosphoinositol turnover

Alpha-2   (2a-2b-2c)—ve formation of cAMP

Alpha –3

Beta-1-2-3 and stimulate formation of cAMP

Beta-3 receptors regulate metabolism are found in adipocytes and their activation by agonists may reduces amount of body fat (Antiobesity)

NE and drugs

*MAOIs

*SNRIs

1-TCAs

2-venlafaxine

3- Bupropion

4-Nefazodone

* Mirtazapine (remeron)block presynaptic alpha2 receptors so increase release of NE

*Not the immediate effect of the drug alone that result in improvement but the delayed effect of down regulation of postsynaptic beta receptors

* Clonidine is alpha 2 agonist that lead to decrease release of NE

*Yohimbine is alpha2 antagonist that correct sexual side effects of antidepressant drugs esp SSRIs

*Beta-blockers used in ——-

*Aldomet is a competitive antagonist for aromatic amino acid decarboxylase so decrease synthesis of NE and E .

Serotonin

*Tracts from upper pons and midbrain (raphe nucleus) to cortex and limbic system

*Synthesis in presynaptic terminal from tryptophan

*Dietary tryptophan can affect serotonin level

*Decreased dietary tryptophan leads to irritability and hunger

*Increased dietary tryptophan lead to relief of anxiety , sleep and improved mood.

*Metabolized as NE

*The transporter which transport 5HT from synaptic cleft to the cell again has many subtypes due to genetic polymorphiskm so there are variations between people in level of transporter and hence anxiety

5HT Receptors

There are 14 type

5HT1  (A-B-C-D-E-F)

5HT2  (A-B-C)

5HT3

5HT4

5HT5 (A-B)

5HT6

5HT7

All are working through G-protein except 5HT3

Buspirone	agonist	5HT-1A
Clozapine	antagonist	5HT-2

Side effects of serotonin agonists

1-Sexual side effects due to spinal cord pathways

2-GIT symptoms due to intestinal receptors

3-Akathesia and agitation due to basal ganglia receptors

4-Insomnia or somnolence due to brain stem receptors

*Nefazodone and trazodone

Inhibit 5HT2 receptors

Stimulate 5HT1 receptors

Block reuptake of serotonin

Net effect is 5HT1 agonist

*Fenfluramine and dexfenfluramine (redux) stimulate release of serotonin from vesicles and are acting as anorectic drugs.

* L-Tryptophane can be used orally but in the past it leads to esinophilia –myalagia syndrome so withdrawan by FDA

 

 

Serotonin and psychopathology

Biogenic amine hypothesis of mood disorders

Too little serotonin in depression

Too much serotonin in mania

Permissive hypothesis of mood disorders

Low levels of serotonin permit high levels of NE which lead to depression or mania

Serotonin hypothesis of  schizophrenia

Schizophrenia is due to misregulation between DA and serotonin

Serotonin hypothesis of anxiety disorders

 

Acetylcholine

 

*Tracts from nucleus basalis of Menyert to c. cortex and limbic system.

*Nucleus basalis of Menyert sometimes degenerated in Alz D and Down’s  syndrome

*Synthesis from

Acetyle CO-A + Choline 1→  A.Ch

 

*The synthesis enzyme is choline acetyltransferase

*Metabolized by acetyle choline estrase

Cholinergic receptors

Muscarinic  M1-2-3-4-5

Antagonized by atropine

Nicotinic receptors are ligand gated ion channels

The receptor itself is formed of alpha, beta, gama, and delta subunit. But it may not contain the all subunits

Acetylcholine and drugs

*Anticholinergic (antimuscarinic ) drugs are used to overcome extrapyramidal effects of APD because there is a balance between A.Ch and DA in basal ganglia so when DA is blocked the balance is impaired.

*Antimuscarinic side effects are dryness of mouth , ….etc

*Donepezil (aricept) block breakdown of cholin estrase enzyme so increases A.Ch  used in Alz D   

*Nicotine increases synaptic connections in the hippocampus so supports short term memory (nicotine agonists are under trials in treatment of Alz D

Acetylcholin and psychopathology

It is related to Alz D and may be other types of dementia

May be related to mood and sleep disorders

Histamine

Three types of receptors

H1 →increase IP3 and DAG

Block of H1 lead to antiallergic effects, sedation, weight gain, and hypotension

H2 →increase cAMP

H3 →regulate vascular tone

 

NT	Precursor	Synthesis E	Metabolism	Receptors	Increase in	Decrease in	Drugs acting are
DA	Tyrosine
NE	Tyrosine
Epi	Tyrosine
Serotonin	tryptophan
Glutamate			reuptake
Acetyle choline	Nucleus basalis of Menyert *The synthesis enzyme is choline acetyltransferase		*Metabolized by acetyle choline estrase	Muscarinic  M1-2-3-4-5 Nicotinic receptors are ligand gated ion channels The receptor itself is formed of alpha, beta, gama, and delta subunit.	Schizophrenia Mood dis Sleep dis	Alzhiemer	* atropine is muscarinic antagonist *Donepezil (aricept) block breakdown of cholin estrase enzyme so increases A.Ch  used in Alz D
Histamine				H1- H2- H3	schizophrenia	Weight gain	Antihistaminic drugs ADD APD

Peptides

1-Endogenous Opioids

*4 types

Endorphins

Enkephalins

Dynorphins

Endomorphins

*Related to control pain , stress and mood

*They have potentiating effects on glutamate and adrenergic neurotransmission

*Related to addiction

2-Substance P

*Related to pain perception

*It is the afferent nerves NT

* May be related to HD, Alz D, and mood disorders

3-Neurotensin

It is found in the same neurons of DA so may be implicated in schizophrenia

4-CCK

May induce panic attacks in patients with panic disorders

May be related to pathophysiology of schizophrenia, eating and movement disorders.

5-Somatostatin

GH inhibiting factor and may be related to HD and Alz D

6-Vasopressin and Oxytocin

Related to mood disorders

7-Neuropeptide Y

It stimulate appetite so its antagonists may be used in obesity

 

HYPOTHALAMUS

It is a mass of nuclei

Supraoptic and paraventricular are clearly delineated

Function of hypopthalamus is homeostasis

Control of autonomic functions

Regulation of circadian rhythm

Regulation of appetite

Control of water balance

Control of endocrine glands

Regulation of body temperature

Regulation of sexual functions

Regulation of metabolism

Control of motivation and emotions

1-Control of autonomic functions

 

Midline posterior

–

–

–

–

–

–

Midline anterior

 

Anerior hypothalamus controls parasympathetic

Posterolateral hypothalamus controls sympathetic

Dorsomedial controls adrenal medulla

Middorsal regions control vasodilatation of muscles

2-Regulation of circadian rhythm

Study of regular biological rhythm is called chronobiology

In human being there are some rhythms that are present almostly in every process eg. Neurotransmitter release, hormoines, sleep, receptor senstivity, etc.

Rhythms less than a day is called ultraradian

Rhythms of 24 hours is called circadian

Rhtythms more than 24 hours is called infraradian

*Rhythms of one week is called circaseptain

*In resting states all rhythms are said to be in phase and If not said to be out of phase.

Phase delay

Phase advance

*Biological rhythms are set by internal and external Zeitgebers

*Internal Zeitgeber is suprachiasmatic nucleus

*External Zeitgeber are, patterned meal times, work hours, light dark cycle, etc.

*In absence of external zeitgbers circadian rhythm is a bit longer than 24 hours (24.5)

*Lesions of suprachismatic nucleus lead to disturbance of ACTH and melatonin secretion, disruption of estrous cycle

Light or darkness

 

Retina

 

retinohypothalmic tract

 

hypothalmus

 

suprachismatic

 

Pineal body and pituitary

3-Regulation of appetite

*Feeding center in lateral hypothalmus

*Satiety center in ventromediual nuclei

*Feeding center is chronically active and is transiently inhibited by Satiety center

*Glucostate hypotheis of appetite

VMN depend on glucose utilization for its work

It is the only area of brain in need for insulin

If glucose and insulin are available became active and inhibit the feeding center and if not appetite increased so in diabetics appetite is increased

*Other factors controlling appetite include:

amygdala and limbic system

ventral bundle (nor adrenergic fibers inhibit the appetite

serotonin, fenfluramine , amphetamine

size of depot fat (lipostate hypothesis)

temperature of the environment

GIT hormones

GIT distension

Stomach contraction

*After lesion of ventromedial nucleus feeding center became more activated and weight increased but to a certain point at which the new weight is maintained so, it is a set point rather than absolute control.

4-Control of water balance

Occur through regulation of water intake and water loss

Water intake

Thirst center in posterolateral aspect of hypothalamus

Increased plasma osmolality

 

Osmoreceptors (central)

 

Thirst

Water intake

 

Decreased plasma volume

 

Volume receptors (peripheral)and Decreased renal blood flow

 

Thirst and water intake angiotensin release

 

ADH release

Incraesed plasma volume

Water loss

*ADH release from supraoptic nuclei and to lesser extent from paraventricular

*transported to pars nervosa of pituatry through axons of these neurons and stored in vesicles called Herring bodies

It is a neurohormone as it released in blood by nerve cells.

*It is 9 aminoacids

*There are two froms arginin vasopressin and lysin vasopressin human ADH is arginin vasopressin

ADH control reabsorption of water from distal tubules of the kidneys.

Supraoptic N

(neurophysin II= pressophysin)

 

Free hormone in post pituitary

 

 

V 1 receptors ( vessels) V 2 receptors (kidneys)

 

Increase calcium Adenyl cyclase

 

Vasoconstriction cAMP

 

Opening of protein channels

 

Reabsorption of water by hypertonic renal medullary interstitium

 

Control of ADH release

1-Osmolality

2-ECF volume

Volume or stretch receptors

low pressure found in veins

high pressure found in arteries

3-Drugs

Safinace and alcohol decrease ADH

Tegretol, smoking and heroin increase ADH

4-Others

pain, nausea, stress, exercise stimulate release of ADH

Syndrome of inappropriate hypersecretion of ADH (SIADH)

Occurs with cerebral and pulmonary diseases

Pulmonary disorders as cancers there is interruption of afferent I pulses from stretch receptors in great atria and veins to hypothalamus

There is increased release of ADH

 

Increase ECF volume

 

Inhibit release of aldosetrone

 

Hyponatremia

SIADH is treated by Domoclocyclin which decrease renal response to ADH

Why tegretol reduces serum sodium?

Tegretol

 

Release of ADH

 

Increase plasma volume

 

Decrease aldosetrone secertion

 

Loss of sodium

5-Control of endocrinal glands

I-Nervous control

a-Axons of supraoptic and paraventricular nuclei end in posterior pituitary and secret oxytocin and ADH

b-adrenal medulla is controlled by

dorsomedial part of hypothalamus

 

medulla oblongata

 

adrenal medulla

II-Indirect or vascular control

From the median eminence of hypothalamus there is release of tropic hormones  and reach the anterior pituitary through hypothalamo-hypophyseal portal circulation.

They are polypeptides work through cAMP

Release hormones

CRH corticotropin releasing hormone

TRH thyrotropin releasing hormone

GRH growth hormone releasing hormone

GTRH gonadotropin releasing hormone

PRH prolactin releasing hormone

Release inhibiting hormones

Somatostatin inhibit GH

Dopamine inhibit the prolactin

Oxytocin

Synthesis in paraventricular nuclei

Stored in Herring bodies

At first it is formed of larger precuriso called neurophysin I

Acts through incraese of calcium intracellualrly

Functions

1-Milk ejection

Suckling

 

Touch receptors around the nipple

 

hypothalamus

 

anterior and posterior pituitary

 

prolactin and oxytocin

 

synthesis of milk contraction of myoepithelial cells

 

Ejection of milk

 

 

2-Sperm transport in the female genital tract

3-during pregnancy

 

Increased progesterone

 

Decreased sensitivity of uterine muscles to oxytocin

In late pregnancy

 

Decreased progesterone and increased estrogen

 

Increased oxytocin binding receptors in uterus

 

Head of the fetus

 

Cervical dilatation

 

Stretch receptors

 

Hypothalamus

 

Oxytocin

 

Uterine contractions and cervical dilatation

4-In males only

It is responsible for transfer of sperms from seminiferous tubules epidydmis to vas deferance to

5-squeezes apocrine sweat glands

 

release of oxytocin is increased by stress and dec5eased by alcohol

 

6-Regulation of body temperature

Centers

LA Loss center in Anterior hypothalamus

GP Gain center in Posterior hypothalamus

Loss center

1-Vasodilatation of skin blood vessels and sweating

2-Shift of blood from core to the skin (radiator system of the body) where heat is lost by

Conduction

Evaporation (through skin and lung)

Radiation (60% of total heat loss)(in the form of infra red heat rays)

Gain center

Increases Thyroxin

Nor epinephrine

ACTH

Shivering

Excess heat

 

Anterior hypothalamus

Preoptic  area

 

Vasodilatation Inhibit heat producing mechanisms

and sweating shivering, loss of sweating and VC

in case of hypothermia

 

Skin VC

Piloerection

Shivering

Thyroxin release

Sympathetic excitation of heat production

Insulator system of the body

Skin and subcutaneous tissues act as insulator system as its conduction capacity is only one third of  other tissues.

 

Regulation

1-heat sensitive receptors in anterior hypothalamus (preoptic area)

2-cold (more abundant) and warmth (less abundant) receptors in skin.

3-deep body temperature receptors

 

Control of sweating

1-Preoptic area in anterior hypothalamus

 

Sympathetic cholinergic outflow

 

Sweating

2-circulating epinephrine and nor epinephrine can stimulate the sweat glands

 

7-Hypothalamic control of sexual functions

1-Ovulation reflex (ovulation when the female see the male animal) visual impulses stimulates the hypothalamus

 2-Neuroendocrinal reflex (ovulation at the time of copulation)

tactile impulses stimulates the hypothalamus

3-Psychological and emotional conditions

Stimulation of the hypothalamus by cortical impulses affects release of gondotrophic hormones from the anterior pituitary

8-Regulation of metabolism

control of metabolism occur through control of endocrine glands

On exposure to cold

Release of thermogenic hormones

glucocorticoids

thyroxin

Blood glucose level

hypoglycemia stimulates release of

ACTH and glucocorticoids

Epinephrine and nor epinephrine

Stimulates vagus nerve to produce gastric hunger

Control of motivation and emotions

See the limbic system

Thinking

Definition:

It is a pattern of CNS activity characterized by:

Involvement of many parts

Simultaneously or

In a definite sequence

Types

2 extreme thoughts are resent

Cortical type eg vision

Lower centers type eg. Pain

Centers

Cortex

Limbic system

Thalamus

Reticular formation

The cortex determine definite characteristics of thought while all other centers determine general nature of thought

Consciousness

Definition of consciousness:

State of awareness of the self and the environment.

When the term used it means

• awareness of experience

2-intention

3-denotes knowledge of a conscious self.

Consciousness is two parts

1-Awareness which is meaningful understanding of self and environment

Related to diffuse cortical activity.

2-Arousal which is a set of responses to stimuli as pain , movements, etc.

Related to activity of reticular activating system and it acts as switch off to cortical activity and so awareness

Health arousal with impaired awareness called vegetative state and is due to diffuse cortical failure

Unconsciousness

It is a term used in three ways

1-A continuum with consciousness at one end and death at the other end (organic).

2- A continuum from deep sleep to full consciousness

3-Full vigilance towards the immediate object of awareness to total unawareness and unconscious to the object.

Dimensions of consciousness

1-Vigilance (wakeful) versus drowsiness (sleep)

Vigilance is fluctuating and affected by

interest, anxiety,  fear, boredom, enjoyment.

2-Lucidity versus clouding

Lucidity is the clear sensorium, which is the total awareness of all internal and external sensations

Clouding denotes a lesser stage of impairment of all intellectual functions.

3-Consciousness of self

The ability to experience the self

So, conscious means full wakefulness, clear awareness and able to experience the self.

MEMORY

Definition:

Storage of information for future use in

Thinking

Control of motor functions

Control of other functions

Storage mainly in the cortex but can extend down to the cord

Memory is the function of synapses

 

Sensory signals

 

Sequence of synapses

 

Facilitation, facilitated pathways, memory traces, or sensitization

(Increase of intracellular calcium and prolongation of action potential)

 

1-Synapses became more capable for transmission

2-Signals generated within the brain itself causes also synaptic transmission

 

Experiencing of the original information

Memory traces

They are the facilitated pathways

Can be stimulated by the thinking mind

Occur at levels of CNS

Spinal cord for sexual

BG and cerebellum for procedural reflexes

Cortex for intellectual processes

Positive and negative memory

Brain is exposed to a lot of information

 

Limbic region of the brain

 

Decision formation

 

Not important important consequences

 

Inhibition of synaptic pathways facilitation of synapses

(Habituation)

(Decrease calcium in nerve endings)           (Increase calcium and prolongation of AP)

 

Negative memory positive memory

 

 

Classification of memory

	Short term memory STM	Intermediate long term memory ILTM	Long term memory LTM
	7-10 numbers or facts
	Few seconds to few minutes	Minutes to weeks	Life time
	Reverbrating cicuits Presynaptic facilitation Synaptic potentiation	Chemical changes	Structural changes

Short term memory STM

1-Reverberating circuit

 

 

 

 

2-Presynaptic facilitation

more than one presynaptic neuron release neurotransmitters

 

 

 

 

 

+ + + + + + +

 

 

 

3-Synaptic potentiation

Increase entry of calcium to presynaptic neuron

 

Increase release of NT

Intermediate long term memory

1-Studies on large snail aplysia

 

Sensory terminal facilitation T

 

 

 

 

Post synaptic T

 

1-habituation (negative memory)sensory terminal is stimulated alone

2-facilitation (positive memory)both sensory and facilitation terminal are stimulated

Molecular mechanism of habituation

Progressive closure of calcium channel

Molecular mechanism of facilitation

Stimulation of facilitatory terminal

 

Release of 5HT

 

Work on sensory terminal

 

Incraese cAMP

 

Activate protein kinase

 

Phosphorylate part of K channels

 

K channels became clsoed

 

Action potential is prolonged

 

Prolonged activation of calcium pores

 

Increase intracellular calcium

 

More release of neurotransmitter

 

More facilitation of synapse

2-stimuli from separate sources acting on a single neuron lead to long term changes in membrane properties of the post synaptic membrane

Long term memory

1-Structural changes include

Increase in number of

Vesicles

Release sites

Terminals

Neurons (during early years of life)

Dendrites of successive neuron

These changes are blocked by blockers of DNA system

2-Structural changes are stimulated by nerve growth factors

specific type of NGF is necessary for adequate connections to occur and if the specific type is not present connection do not occur and death of the neurons occur.

3-The rule of brain is use it or lose it

multiplication of neurons in early life if associated with stimulating environment and exercises to the child will help neuron to survive and if not inadequate connections followed death is the fate.

Consolidation of memory

For STM to be transferred to LTM and recalled weeks and years after consolidation must occur ie. initiation of chemical and structural changes.

Duration needed?

*5-10 minutes for minimal consolidation and one hour for strong consolidation

*Deep general anesthesia and concussion can prevent consolidation.

How to enhance memory?

1-Rehearsal

*Accelerate and potentiate degree of transfer from STM to LTM

*If the information attracts the mind’s attention it has a natural tendency to be rehearsed.

*With passage of time important memories became more and more fixed in memory stores.

2-Chunking

3-similarities and differences

4-categorization of information

5-similar environment

Role of different parts of the brain in memory

Hippocampus

*Decision making to store or not to store depending on consequences and motivation

*It is especially important for verbal and symbolic learning.

*Lesion lead to

Anterograde or retrograde amnesia

Thalamus

*Help in searching process in memory store house

*Lesion lead to

Retrograde amnesia

Basal ganglia and cerebellum

Responsible for reflexive learning eg sports

DLPFC dorsolateral prefrontal cortex

Responsible for:

Elaboration of thoughts (increase depth and abstraction of thoughts)

Working memory

Working memory

*The ability of the mind to keep track for many bits of information simultaneously and recall of such information for certain thought or action.

*Its main functions are

Prognosticate

Plan

Delay

Consequences of our actions

Solve

Correlates

Control

Recent classification of memory

 

 

Explicit Implicit

Called long term short term

Procedural or 1-episodic sensory

Reflexive or 2-semantic

Motor memory

Physiology of Sleep

Definition Sleep is a reversible unconsciousness state that can be aroused from by sensory or other stimuli.

*Sleep is regular recurrent and easily reversible.

*Sleep disturbance is an early symptom off impending mental illness

NREM stages

Stage I	Stage II	III  (SWS)	IV (SWS)	REM
3-7 C/S	12-14 C/S sleep spindles Slow triphasic K waves	Delta activity 0.5-2.5 C/S Less than 50%	Delta activity 0.5-2.5 C/S Less than 50%	Low voltage random fast activity
Low voltage		High voltage	High voltage
regular

REM

Characterized by

1-Increased physiological functions (paradoxical sleep)

2-Irregular patterns

More variability from minute to minute

3-Hypotonia near total paralysis of body movemments

4-Penile erections

5-Altered thermoregualtion

6-Most REM occur at last third of the night

7-First REM about 10 minutes in duration

Other REMs about 15-40 min

In neonatal period more than 50% of sleep

In adults about 25% of sleep

8-REM duration range from 5 to 30 minutes

9-first REM start after 90 minutes (REM latency).

10-associated with active dreaming with remembering of such dreams.

11-associated with rapid eye movement number of these movement is the REM density.

12-brain metabolism is highly active about 20% more than resting state.

13-EEG showed awake pattern.

NREM

Characterized by

1-Decreased physiological functions

2-Few minute to minute variations

3-Pulse , BP , respiratory rate, BMR and CBF less than awake state

4-stage 3 and 4 ccc by Unusual arousal characteristics:

Disorientation ,disorganized thinking ,amnesia, somnambulism, enuresis, nightmares and night terrors.

5-Less if any rapid conjugate eye movements

6-Lucid purposeful dreams.

7-Most stage 4 occur in first third of night

8-exceedingly restful

9-dreams could occur but not remembered as those of REM as there is no consolidation.

Normal sleep structure

In adults

NREM 75%

I 5

II 45

III 12

IV 13

REM 25%

In newly born,  most of sleep is REM and duration is too much than adults

In old age REM is reduced and total sleep duration reduced. why duration decreased?

-Decrease need to sleep due to

Decrease activity

Decrease anabolism

-Redistribution of sleep through day naps

Why REM reduced?

Atrophy of pineal body and loss of melatonin

Decrease acetyle choline

 

Sleep curve

 

 

1

     2                 REM    2^nd REM   3^rd REM

      3

4

 

Sleep and psychiatric disorders

1-Sleep disturbances in depression is due to cholinergic disturbance it is in the form of

Shift of REM from the last half of sleep to the first

Increased REM Density.

*Drugs that shortened REM like ADD improve depression

*Drugs that increase REM as reserpine produces depression

*Sleep deprivation or restriction reduce REM so improve depression

2-In Alzheimer D REM is reduced

In cases of depression there is shift of this curve to the right (duration of each REM increased).

While in cases of dementia there is shift to the left (duration of REM reduced).

Sleep regulation

Suggested centers and theories for sleep

1-Passive theory of sleep (fatigue of RAS)

2-Raphe nuclei of brain stem sleep

3-Tractus solitarius stimulation of raphe

sleep

4-Diencephalon

rostral part of hypothalamus

diffuse thalaemic nuclei

 

 

Neurotransmitters

1-Serotonin

Tryptophan reduces sleep latency

2-Nor-epinephrine (locus cereuleus)= REM off neurons

Drugs increase firing of locus C lead to marked reduction of REM

3-Acetylecholine = REM on neurons

*Acetyle choline neurons at the upper art of brain stem can stimulate the brain to cause REM

*Muscarininc agonists increase REM sleep

4-Dopamine

it has an alerting effect so APD increase sleep time

5-Process S

there is accumulation of endogenous substance during wakefulness leading to sleep

6-Process C

There is endogenous substance regulating sleep duration and body temperature

7-Muramyle peptide in CSF and urine

8-Nona peptide (blood)

8-Sleep factor (brain stem).

 

During sleep

Sleep centers

 

Stimulate upper pontine nuclei and mesencephalic nuclei

 

Inhibit the cortex

During wakefulness

When Sleep centers lost its activity person became wakeful and wakefulness has natural tendency to be sustained.

Functions of sleep

1-Restoration of normal homeostatic functions

2-Body temperature regulation

3-Energy conservation

4-Satisfying metabolic needs during NREM

NREM functions

Anabolism

Restoration of health

Prevention of lethargy

REM functions

New connections

Cognitive functions

Consolidation

Neurotransmitters

Sleep and the body

Wakefulness enhance sympathetic functions

SWS enhance parasympathetic functions

Sleep  deprivation

1-Total sleep deprivation Lead to  Overuse of certain brain areas which causes

Abnormal behavior

Sluggish thoughts

Psychosis

Irritability

So sleep maintain balance between different areas.

2-REM deprivation lead to irritability and lethargy

3-NREM deprivation hallucination, delusion and ego disorganization.

Sleep requirements

Short sleepers

Less than 6 hours

Efficient, ambitious and socially adept.

Long sleepers

More than 9 hours

They have more REM periods

Mildly depressed, anxious and withdrawn.

 

Parasomnias

Nightmare	Night terror	Sleep walking	Sleep  related bruxism
Late in night	First third	First third
REM	3-4	3-4	Stage 2
Mild fear and anxiety	Terror, behavioral , anxiety s Then return to sleep	Complex acts may occur then return to sleep	Sleep talking
	Boys>Girls Minor neurological abnormality Stressful family prob	Boys>girls Run in families Mild neurological abnormality	In all stages
Dream	No dream		REM sleep behavior disorder
BDZ-TCA	Small dose valium at bed time	Stage 3&4 suppressants	Loss of atonia of REM so, violent complex behaviors TTT: clonazepam and carabmazepine

EEG

There is continuous electrical activity in the brain. The  intensity and pattern of this electrical activity is determined by RAS.

Discharge from single neuron can not be recorded and simultaneous discharge of many neurons is important to record EEG

	Alpha	Beta	Theta	Delta
Frequency C/S	8-13	>13	4-7	2-3
amplitude	50 mv	less	more	300 mv
Place	Occipital	Frontal	Temporal
Normality	Normal	Eye opened Anxiety Drug induced	Below 12 years During sleep	In baby During sleep
source	*Non specific reticular nuclei *Thalemic nuclei *Brain stem *(diffuse thalamo cortical system)			Cortical neurons
Transection above thalamus	abolish			persist
Other characters	sinusoidal

Basal ganglia BG

1-Caudate nucleus CN

2-Lentiform culceus

Putamen P

Glopus pallidus GP

Cuadate and putamen are called corpus striatum CS

3-Substantia nigra SN, Red nucleus RN, subthalemic neuclei STN are functionally related to the BG

Connections

 

Rf reticular formation

ION inferior olivary nucleus

Red Nucleus

RF

ION

Hypothalamus

 

 

 

 

 

 

(Extra pyramidal tracts)

Rubrospiunal

Reticulo spinal tract

Cortico pallido thalamo cortical circuit

Area 4 S (extrapyramidal pre motor area)

 

Corpus striatum

 

Glopus pallidus

 

Thalamus (ventrolateral nucleus)

 

Inhibit motor areas 4-6-4S

 

This circuit responsible for controlling activity of motor cortex

Dysfunction lead to involuntary movements

Functions of the basal ganglia

• primary motor area in birds

2-automatic movements in higher animals

eating

posture

defense

sexual activity

3-in man contribute in

	Lesion
A-Controlling      Planing      Programming of movements
b-subconscious automatic movements (Corps striatum)	Loss of automatic movements
c-Suitable tone and posture (GP)	Tone disturbance
d-in decorticated human (equilibrium and subconscious movements)	Complete paralysis
e-inhibit muscle tone	Rigidity
f-control excess activity in cortex	Involuntary movements

 

Basal ganglia

 

 

Thalamus and cortex brain stem

Reticulospinal and rubrospinal

 

Pyramidal and extrapyramidal

 

Muscle

 

Chorea is related to corpus striatum

Hemibalismus is related to opposite subthalemic nuclei

Athetosis is related to lentiform nucleus

Parkinson is related to substantia nigra

Psychosomatic effects of behavioral system

Brain

 

Pyramidal tract ANS pituitary

 

Muscles

 

Proprioceptors

 

RAS

 

ANS

	sympathetic	Parasympathetic
Activity	Diffuse	Focal
symptoms	HR, BP, pupil, GIT, BMR	Eg diarrhea

 

Oral Question

eg in Mania and anxiety

Increase nor epinephrine and muscle activity

 

 

Stimulation of proprioceptors

 

Intense feedback

 

RAS

 

Insomnia

 

Body and mental fatigue

Limbic system

It is the entire neuronal circuitry that controls emotional behavior and motivational drives.

Hypothalamus from physiologic point of view is the one of the control elements of limbic system.

 

 

 

1

2 3

6

4

5

Limbic cortex

1-cingulate cortex

2-orbitofrontal cortex

3-part of top of corpus callosum

4-subcallosal gyrus

5-ventromedial surface of temporal lobe

6-uncus and hippocampus

It is a link between neocortex and lower limbic structures.

 

Limbic Circuits

1-Papez MaClean circuit

HMTC

 

 

 

 

 

Hippocampus- mammilary body, anterior thalamic nuclei, and cingulate

 

2-ASHM

Amygdala

 

Stria terminalis

 

Hypothalamus

 

Medial forebrain bundle MFB

 

Brain stem limbic cortex

Functions of limbic system

1-Olfaction

2-Feeding behavior

Stimulation of amygdala licking and chewing movements

Lesion of amygdala     hyperphagia and omniphagia

3-Autonomic functions through connections with hypothalamus

4-Memory especially hippocampus

5-Biological rhythms

6-Attention

hippocampus corticofugal fibers     Rf attention

7-Sexual behavior

Spinal and lower brain centers regulate sexual reflexes

Limbic and hypothalamus regulate urge and sexual behavior

Bilateral lesions of amygdala lead to hypersexuality

8-Control of emotions

9-Control of motivation

8-Emotions

*Emotions are complex phenomena triggered by stimuli

*Emotional behavior is not an on off phenomena  by the will but it has prolonged after discharge so response is prolonged mor than duration of the stimulus.

*Components of emotions

Emotional expression (physical changes)

Emotional experience (affective component)

Cognitive component

Sensory tracts

 

Psychosensory cortex

 

Association areas

 

Limbic system

 

Hypothalamus Mammilary body hippocampus

 

ANS Thalamus memory formation

(Cognitive aspect)

Expression       integrated by Orbitofrontal

 

Experience

 

Hypothalamus

 

Lateral VMN ventromedial nucleus

 

Rage center tranquility center

 

So lesion of

Lateral N VMN

 

Extreme passivity and tranquility rage

Decrease drinking and eating(feeding center) increase drinking and eating

 

Fight and flight

Flight reaction or fear

Due to stimulation of amygdala and hypothalamus

Somatic effects eg seeking escape

Autonomic effects eg papillary dilatation

Disappear if amygdala destroyed

Rage or fight reaction

Due to stimulation of amygdala and lateral hypothalamus

Somatic effects

Autonomic effects

So the two reactions are close to each other. Animal may be firstly tries to escape and if cornered it fights.

Rage and placidity

Rage centers are

1-Lateral N

2-amygdala

Placidity centers are

1-VMN

2-neocortex works by inhibiting lateral N

Sham rage

Severe rage in response to trivial stimuli due to

Removal of neocortex or

Destruction of VMN

It is not sham but true rage because it includes sympathetic effects, somatic effects, and cognitive element as the animal direct his rage to certain object which provoke him

Oral Why hypoglycemic patients have shame rage?

9-Motivation

A-Reward areas

Stimulation of reward areas along MFB

Septum amygdala- thalamus- BG- basal tegmentum

 

Pleasant feelings

 

Increase motivation

 

Lateral hypothalemic N is included

Weak stimulation lead to pleasant effects

Strong stimulation lead to unpleasant effect and rage

B-Punishment or avoidance areas

Stimulation of

Posterolateral hypothalamus- dorsal midbrain- grey surrounding aqueduct- amygdala – hippocampus

 

Unpleasant feeling

 

Decrease motivation

 

Punishment areas act by inhibiting reward areas

So fear take precedence over reward

 

Importance of reward and punishment is control of motivation, learning and memory

Physiology of Pain

Pain is a complex sensation

It has cognitive (psychological) component and

Physiological component

Affective component

Pain has specialization but not specificity

Certain receptors are important for perception of pain but receptor alone is not specific

Pain threshold

The least stimulus lead to pain

Affected by physiological factors

Pain tolerance

The most severe stimulus that can be tolerated for a reasonable period of time

Affected by psychological factors

 

*Social and cultural factors affect pain perception

Control of pain

Common sensical theory of pain

Stimulus receptors brain

Against this theory

No pain center

After transection of the cord there is pain perception

Gate theory of pain

Melazack and Wall

 

Cognitive control Descending inhibitory control

 

 

 

Large C fibers

 

 

Receptors   SGR ——I—- action

S +++++ system

 

 

Small  fibers

 

Factors open the gate

Cognitive factors (anxiety)

Muscle tension increase s fibers impulses

Factors close the gate

Cognitive factors by decreasing impulses in s fibers (soldiers)

Relaxation and biofeedback decrease muscle tension and s fibers impulses

Periaqueductal grey can directly close the gate (eg in stress)

Neurotransmitters

Substance P from dorsal root gagnlia to SGR for pain transmission

Serotonin from higher centers to the SGR (inhibitory to pain transmission )

Endogenous opiates (inhibitory for pain transmission)

Oral question Dr Okasha Dr Afaf- Dr Fatema Dr Refaat El-Fikki

Brain analgesia system= supra spinal control of pain

Periaqueductal grey and hypothalamus send inhibitory imupulses to close the gate (serotonin)

Dr Moustafa Kamel

Physiology of sexual cycle

1-Appetitive stage = desire stage

Characterized by sexual fantasies

2-Excitement stage

Could be triggered by physical or psychological factors

Characterized by erection in males and vaginal lubrication in females

Arousal is the amount of excitement or erection while arousability is the rate of erection or arousal

3-Platue stage

4-Orgasmic stage

charachetrized by ejaculation in males and uterine and pelvic contractions in females

5-Resolution stage

Take shorter time in males than in females

6-Refractory period stage

Only in males and increased with age

Physiology of sexual functions

Cortex is responsible f or cues and inhibition of sexual impulses and delaying it to acceptable situations

Limbic system responsible for expression of sexual behavior

Autonomic nervous system is responsible for changes in the periphery

Endocrinal system responsible for sex hormones

Spinal cord is responsible for sexual reflexes

Serotonin inhibit orgasm

Acetyle choline and nor epinephrine help orgasm

Prolactin inhibit erection eg APD

Nitric oxide help erection

cGMP help erection

Gender

Sexual identity is the biology

Hormones

External organs

Internal organs

All embryos are females then under effect of y chromosome there is release of male androgens that modify sex from female to male

Gender identity

Subjective feeling of being male or female and is affected by psychological and cultural factors

Gender role

The external expression of gender identity ie how the person behave in social context

Sexual orientation

Heterosexual, homosexual or bisexual

 

 

Physiology of eye movements

1-Saccadic eye movements

jumping of eye from one position to another by very fast manner about 700 degree in sec

Helps to fix the object on similar sites on both retinae

Controlled by area 8 and ocular cranial nerves nuclei

2- Smooth pursuit eye movements

Help to fix eye on a moving object

Controlled by occipitoparietal region on the same side

3-Nystagmus

Occur normal in

Nystagmoid movements

optokinetic nystagmus

Children

Blind people

Caloric test

Physiology of biofeedback

A kind of sixth sense that enable people to see or hear activity inside their bodies

It is a training to put involuntary functions under voluntary control

Types

EMG Electrodes for tension headache , anxiety, vaginesmus, pain disorder

Heart rate electrodes for anxiety

Blood pressure electrodes for hypertension

Skin electrodes (galvanic skin response) for Rynaude disease

Reticular formation

Filtration hypothesis of schizophrenia

Narcolepsy

Attention deficit hyperkinetic disorder ADHD

Sensory deprivation

Oral Q one therapy depend on reticular formation?

Hypnosis

Dr Afaf Only

Adaptation and habituation

Emotions

Memory

Pain modulation

Oral question

Hormones and behavior

ACTH and depression

Prolactin and oxytocin and maternal behavior

Psychosomatic disorders

Definition

Examples Peptic ulcer

Mechanism Parasympathetic through vagus

Endocrinal through cortisol

Dreams

Physiological theory

REM on neurons (acteyl choline)

REM off neurons (nor epinephrine)

2 hours per night occupied by dreams

REM and NREM dreams

REM	NREM
Less related to reality less like normal thought	Like normal thought
remembered	Not
More vivid and emotional	Less

Social learning theory

Dreams are learned response from every day listening to each other

Also it is affected by environmental stimuli during sleep

Cognitive theory

Dreams are always related to thoughts that preoccupy our mind.

 Affected by something in every day waking life but with reshaping and recreation with new illogical forms

dreams may be reach in creative ideas eg Kofka Benzene ring

Psychodynamically

Unconscious wishes, needs and conflicts from earliest childhood events up to events in adulthood that are repressed or unaccepted .

All are symbolic

 

Men dreams are more aggressive

Children dreams about scary animals

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

8

 

 

 

prefrontal area          area 8            area 6          area 4 S            area 4             area 1, 2, 3 5&7 somatosensory asso area

 

        thinking          conjugate      gross vol move          fine vol mov  fine touch body image

       planning eye – mus tone     – mus tone       + mus tone    weight discrmi hemiparesis

      intelligence       movements   – grasp              viberation cortical sensory loss

      attention           to opposite autonomic              grades of temp loss of OK nystagmus

     self control side automa mov lower quadrentic hemianopia

     social behavior domi non dominant

     memory ideational and dressing

     autonomic functions ideomotor apraxia apraxia

      emotions dyslexia visuspatial

grestmann synd anosognosia

              SSA-II tactile agnosia topographic memory loss

               elaboration

              of sensory

               data

 

 

 

complex hallucinations

emtional and behavioral change

upper quadrentic hemianopia

uncinate fits

dominant non dominnat

verabl visual

wernick’s aphasia spatial relations

agnosia

amusia

 if bilateral gives Korsakoff and Kluver Bucy syndromes