neurotransmitters & neuromodulators

7/24/2019 Neurotransmitters & Neuromodulators

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Neurotransmitters &Neuromodulators


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oncepts you s oualready know before this

lecture Cell membrane ion channels Resting membrane potential

Local potentialTemporal summationSpatial summation

Action potential EPSP IPSP


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Types of Synapses in theCNS


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Presynaptic Inhibitionand Facilitation

Axoaxonic synapses mediatepresynaptic inhibition and facilitation,eg present in the spinal cord to

regulate the propagation ofinformation to the brain

Interneurons regulate the ability of thepresynaptic neurons to releaseneurotransmitters by changing theamount of Ca!!in"ux to thepresynaptic neurons


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http://www.ncbi.nlm.nih.gov/books/NBK11164/

Electrical vs ChemicalSynapse


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Type Electrical Chemical

Length ofsynapticcleft

#$ nm %&'(& nm

Cytoplasmi

c continuity

)es *o

Structure +ap unction Presynaptic-esiclesPostsynapticreceptors

Agents oftransmission

Ion current.electrical/

*eurotransmitters .chemical/

Synapticdelay 0irtuallyabsent 1 2'$ ms


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Dobrunz,

!""!

Chemical Synapse


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Synaptic Communication

Total 6 of action potentials reaching thepresynaptic terminal directly in"uencesthe amount of neurotransmitter released

7excitatory stimuli to the presynapticneuron cause increased 6 actionpotentials reaching the presynapticterminal

7duration of excitatory stimuli to thepresynaptic neuron cause a longerseries of action potentials reaching thepresynaptic terminal


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NE!"#T"$NS%ITTE"S$N NE!"#%#!'$T#"S


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(hat is aNeurotransmitter)

It is synthesi8ed in the neuron It is present in the presynaptic terminal It is released in amounts su9cient to

exert an action on the postsynapticneuron or e:ector organ

It is remo-ed from the synaptic cleft bya speci;c mechanism

Synaptic -esicle cyclinghttp


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(hat is aNeurotransmitter)

>hen administered ?exogenously@ .egdrugs/ in reasonable concentration, itmimics the action of the endogenously

released neurotransmitter exactly Itacti-ates the same ion channels orsecond messenger system in thepostsynaptic cell

Some de;ne neurotransmitters toinclude neuromodulators that act aayfrom the synaptic cleft .4lumefeld, %&2&/

Schart8,


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(hat is aNeuromodulator)

Act at a distance aay from the synapse Bodulate acti-ity of many neurons Released into extracellular "uid The same chemical substance can act

either as a neurotransmitter orneuromodulator

E:ects last minutes to days

*eurotransmitters and neuromodulatorscan be released simultaneously


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Functions ofNeurotransmitters

Bediate communication beteen neuronsor the end'organs through fast excitatory.EPSP/ or inhibitory .IPSI/ postsynapticpotentials .2 ms/

3irectly opening ligand'gated ionchannels on postsynaptic membrane

Slo'acting neuromodulation, occurringo-er 2&&ms to minutes

Indirect opening ion channels oracti-ation the cellular signaling cascades


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Neurotransmitter"eceptors

Receptors are often named accordingto the neurotransmitters to hich theybind, eg +A4AA, +A4A4, $'DTreceptors

The same neurotransmitter may bindto se-eral types of receptors, egSerotonin

The e:ect of neurotransmitters on apostsynaptic neuron is determined bythe type of receptors present on itsmembrane, eg Ach, *orepinephrine


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%echanisms+ irect

$ctivation of IonChannels

*eurotransmittersbind to receptors thatare part of the ligand'gated ion channels

and directly open theion channels


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%echanisms+ Indirect

$ctivation of IonChannels

*eurotransmittersbind to receptors thatare separate from theion channels, andindirectly open the ionchannels by acti-atingthe +'protein This

process in-ol-eschanges in themetabolism of the cell


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*na ransm ss on%echanisms+ $ctivatin*

Intracellular Si*nalin*Acti-ation of the +'protein second'

messenger systemcan trigger theintracellular signalingcascade This process

has long lastinge:ects on regulatinggenes expression andneuronal groth

4yrne, 2F


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Termination of SynapticTransmission

Remo-ing neurotransmitters3i:usion< remo-e a fraction onlyEn8ymatic degradation< eg

acetylcholinesterase

ReuptaGe< most common, eg serotonin 3esensiti8ing receptors by

Receptor internali8ation< folding thepostsynaptic membrane containing thereceptors into the cell

Receptor inacti-ation

C


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CommonNeurotransmitters and

Neuromodulators Amino AcidH+A4A

H+lutamate.+lu/H+lycine .+ly/

CholinergicHAcetycholine

.ACh/

AmineH3opamine .3A/HSerotonin .$'

DT/H*orepinephrin

e .*E/

PeptideHSubstance PHEndorphins


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$mino $cid+ ,$-$

ast'acting BAJKR inhibitoryneurotransmitter found in the entire C*S,eg inhibitory interneurons in spinal cord

Pre-ents excessi-e neural acti-ity4arbiturates mimics the action of +A4A

and are used for sedation, asanticon-ulsants

4aclofen, a muscle relaxant to controlmuscle spasticity, increases presynapticrelease of +A4A


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$mino $cid+ ,lutamate.,lu/

ast'acting BAJKR excitatoryneurotransmitter found in the entire C*S

In-ol-ed in learning and memory +lutamate is present in a ide -ariety of

foods, eg BS+K-eracti-ity of glutamate may cause

sei8ures

Excitotoxicity


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,lutamate "eceptors

ABPA< ligand gated receptor *B3A< ligand' and -oltage'gated receptor

Postsynaptic neuron must depolari8e

hen the +lu binds to the *B3Areceptor in order to open the gate

Prolonged opening of ion channelsresulting in long'term potentiation .LTP/

Betabotropic glutamate receptor< indirectacti-ation by +'protein pathay


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$cetylcholine .$Ch/

%$0#"neurotransmitters in PNS1 $NSast'acting e:ect< act at neuromuscularunction, eg *icotinic receptors

Slo'acting e:ect< regulate DR, A*Sfunction, eg Buscarinic receptors

Primary as a neuromodulator in C*S

Controls locomotion, arousal

acilitate attention, memory, learning


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Nicotinic %uscarinic

4ind nicotine 4ind muscarineLinGed to ionchannels

LiGed to %ndmessenger systemthrough + protein

ast and briefresponse

Slo and prolongedresponse

Located at

neuromuscularunctions,autonomicganglia, and some

C*S

ound on myocardial

muscle, certainsmooth muscle, insome C*S regions

Choliner*i


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Choliner*ic

Pro2ection

Systems

4lumefeld,


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$cetylcholine

Applying electrical stimulation topontomesencephalic region of thebrainstem elicits coordinated locomotormo-ements

3rugs that blocG the cholinergictransmission in the brain causes deliriumand memory de;cits3egeneration of cholinergic neurons in the

basal forebrain may be associated ithmemory decline in $l3heimer4s disease


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%yasthenia ,ravis .%,/

ACh receptors on muscle membranesare destroyed >eaGness becomesmore se-ere ith repetiti-e use of amuscle

Rx< Anticholinesterase inhibits thecholinesterase from breaGing donACh


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%yasthenia ,ravis .%,/

&'(uc'( )*+ $mplitu('sov'r r'p'titiv' muscl'contr$ctions.


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$mines+ opamine .$/

Produced in substantia nigra of basalganglia and -entral tegmentum

Primarily an inhibitory e:ect in C*S

All 3A receptors are %ndmessengersystems to suppress the acti-ity ofCa!! channels

A:ects motor acti-ity,moti-ation=reard beha-ior, andcognition


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opamine Pro2ectin*System

B+ imbic -r'ront$l

*ov'm'nt &'w$r( orking *'mor0

((iction tt'ntion

euro o* c on t ons


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euro o* c on t ons$ssociated with

opamine .$/ParGinsonMs 3isease Case< N3A in basalganglia3epression=Cogniti-e< N3A in forebrain

3rug addiction< cocaine andamphetamines interfere ith 3AreuptaGe into the presynaptic neurons,

alloing 3A to acti-ate receptorsrepetiti-elySchi8ophrenia< too much 3A


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$mines+ Serotonin .567T/

Produced in raphe nuclei and +I tract Serotonin regulates sleep'aGe cycle,

cognition, perception of pain, breathing,

temperature, mo-ements, and mood Serotonin is associated ith depression,anxiety, obsessi-e'compulsi-e disorder,aggressi-e beha-ior, certain eating

disorders .release serotonin Nappetite/ Serotonergic neurons N;ring during sleep


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$mines+ Serotonin .567T/

Serotonin is ?happiness hormone@Serotonin Nperception of pain Lole-els of serotonin are associated ith

depressionPro8ac .antidepressant/ is a selecti-e

inhibitor of serotonin reuptaGe .soserotonin stays in the synaptic cleft

longer to bind ith receptors/SI3S may be associated ith defected

serotonergic neurons


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Norepinephrine .NE/

Regulate functions of A*S, thalamus,and hypothalamus

Bodulate attention, sleep'aGe cycle

*oradrenergic neurons N;ring in sleepAttention'de;cit disorders if often

treated ith medications that enhance*E transmission

7le-el of *E is associated ith -igilance,7alertness, and ?;ght'or'"ight@ response


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Norepinephrine .NE/

*oradrenergic neurons in-ol-e insympathetic functions such as bloodpressure control

Similar to Serotonin, *E alsoNperception of pain in the C*S, andplays a role in many psychiatricsyndrome

N*E can cause depression7*E can cause anxiety .panic attacG/


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SerotoninPro2ection

System

Noradrener*ic

Pro2ectin*Systems

Blum''l(, !"1"


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7istamine

ound mainly in the hypothalamus ound mostly outside the ner-ous

system in mast cells that mediate

immune responses and allergicreactions Role of histamine in the brain

Baintain the alert state

Excitatory e:ects on thalamusAntihistamine medications can cause

drosiness by blocGing C*S histaminereceptors


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Peptides+ Substance P

Released from the terminals of somesensory ner-e ;bers

*eurotransmitter function in thenocicepti-e pathaystimulates free ner-e endings at the

site of inury and transmit painsignals from the periphery to the C*S

*euromodulator function in the chronicpain syndrome increase pain perception


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Peripheralsensiti8ationfolloing celldamage Painsignals cause the

free ner-e endingsto releasesubstance P$'DT outside the

ner-ous systemstimulates thenocicepti-e freener-e endingsSP'substance PDauser, %&2&

ept es+ n o*enous


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ept es+ n o*enous#pioids

.endorphin1 enkephalin1dynorphin/

4odyMs natural painGillers

Inhibit C*S neuronsin-ol-ed in theperception of pain

Exercise increasesendogenous opioids


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Nitric #8ide .N#/

An free radical, highly reacti-e,di:usible gas molecule ithneuromodulator e:ects

*K is important in the regulation ofcerebral blood "o, neurotransmission,long'term potentiation, excitotoxicity.ie neuronal death/

*K cause blood -essels to dilate *K in excess is toxic to cells

neurotransmitters & neuromodulators

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