Neurophysiology II - uniba.sk · 2020. 3. 12. · Cholinergic system Basic facts •1929: izolation of acetylcholine from hourse spleen (Dale and Dudley) •1936: proof of acetylcholine

Neurophysiology II

Synapses, neurotransmitters and neuromodulators

Boris Mravec 2020

Signals transmission

• coordination of cells activities

• transmission of signals from internal environment

• transmission of signals from external environment

autocrine paracrine

endocrine synaptic

Signals transmission

Transmission of signals in the nervous systemFunctions

Transmission of signals in the nervous systemFunctions

Transmission of signals in the nervous system

Transmission of signals in the nervous systemDysfunctions

depression

drugs addiction

schizoprenia

Alzheimer’s disease

Parkinson’s disease

...

Transmission of signals in the nervous system

History

• model of brain activity always reflected current dominant technology of certain period

of time

Transmission of signals in the nervous systemChronology of research

Transmission of signals in the nervous systemChronology of research

Year Discovery Researcher

1866 blockade of neuromuscular transmission by curare Vulpian

1877 suggestion of partial chemical transmission on

neuromuscular junction

Du Bois Reymond

end of the 19th century concept of neural theory Ramón y Cajal

1904 suggestion of chemical transmission in nervous system T. R. Elliott

1914 chemical transmission in autonomic nervous system Dale

1926 confirmation of chemical transmission of the vagus nerve Otto Loewi

Proof of chemical basis neurotransmissionAcetylcholine

Schema of experiments confirming release of "vagus substance" (acetylcholine) from nerve endings of the vagus

nerve. Otto Loewi, 1921

In the year 1936 he received Nobel price for physiology or medicine ("for their discoveries relating to chemical

transmission of nerve impulses").

Electrochemical principle of signal transmission









Debanne et al., 2013


Transmission of signals between neurons

Transmission of signals in nervous system

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Transmission of signals in nervous systemDifferent Types of Intercellular Communication in the Central Nervous System

Transmission type source/target

ratio

source/target

distance

source/target

delay

Gap-junction 1:1 2-3 nm msec

Membrane juxtaposition (ephapsis) 1:1 10 nm msec

Closed synaptic transmission 1:1 20-50 nm msec

Paracrine transmission

Open synaptic transmission 1:n, n>1 – n >>1 100 nm-mm msec-min

Non-synaptic source 1:n, n >>1 1 µm-mm sec-min

Endocrine-like transmission

Nerve-bundle-associated 1:n, n >>1 mm min

Paravascular fluid circulation 1:n, n >>1 mm min

Transmission in cerebro-spinal fluid 1:n, n >>1 mm-cm min

(Zoli and Agnati, 1996)

Transmission of signals in nervous systemDifferent Types of Intercellular Communication in the Central Nervous System

Electrical synapse Chemical synapse

Transmission of signals in nervous system

Electrical synapse

• width of synaptic cleft: ~ 3,5 nm

• synaptic delay: ~0,1 ms

Chemical synapse

• width of synaptic cleft: ~ 20-40 nm

• synaptic delay: ~1-5 ms, seconds to minutes

(Felten and Shetty, 2009)

Composition of chemical synapses

Processing of signals at chemical synapses

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Nonsynaptic chemical transmission in nervous system

• distance of varicosities from target membrane: ~ 2-100 µm

• „synaptic“ delay: from ms to minutes

Nonsynaptic chemical transmission in nervous system

Nonsynaptic chemical transmission in nervous systemMediators of transmission

• norepinephrine

• dopamine

• serotonin

• acetylcholine ?

• NO ?

Characteristics of neurotransmitters

• synthesis in neuron

• localization in presynaptic nerve ending

• release from presynaptic nerve ending to synaptic cleft evoked by action

potential

• binding on postsynaptic (sometimes also on presynaptic) receptors evoke

specific response

• neuronal or synaptically localized mechanisms removing or inactivating

neurotransmitter

• exogenously applied neurotransmiter elicits identical response as its

endogenous release

Characteristics of neurotransmitters

Transmission of signals by chemical synapse

• transsynaptic signalization

• transmembrane signalization

• transcytoplazmatic signalization

• transnuclear signalization

Transmission of signals by chemical synapse

Transmembrane signalization

ionotropic receptor metabotropic receptor

Transcytoplazmatic signalization

Transcytoplazmatic signalization

Transnuclear signalization

Classification of neurotransmitters

Chemical group Example

Small molecule neurotransmitters

Ester of choline acetylcholine

Monoamines

Catecholamines dopamine, norepinephrine, epinephrine

Indols serotonin (5-hydroxytryptamine)

Imidazols histamine

Amino acids

Acidic glutamate

Basic γ-aminobutiric acid, glycine

Purines adenosine triphosphate, adenosine

Steroids pregnenalone, dehydroepiandrosterone

Gas NO, CO

Eicosanoids prostaglandins

Large molecule neurotransmitters

Peptides enkephalins, endorphins, cholecystokinin, substance P

Neurotransmitters with small molecule

Amino acids

Neurotransmitters of „fast“ transmission of signals

Excitatory

- glutamate

(aspartate ?)

Inhibitory

- GABA

- glycine

(taurine, proline, ß-alanine ?)

Glutamatergic system

Glutamatergic systemBasic facts

• 1963: incorporation of glutamate between neurotransmitters (K. Krnjevic and

Phillips)

• 1971: demonstration of high-affinity reuptake of glutamate – basis for methods of

glutamatergic neurons identification (Wofsey)

• main excitatory neurotransmiter in almost all regions of CNS

• approximately 50-60% neurons of CNS are glutamatergic

• via binding on ionotropic receptors increase transmission of cations

Glutamatergic systemSynthesis of glutamate

Glutamín

Glutamát

Glutamináza

HOOC CH2

CH2

CH COOH

NH2

C CH2

NH2

O

CH2

CH COOH

NH2

NH3

HOOC CH2

CH2

CH COOH

NH2

Glutamatergic systemReceptors for glutamate

Ionotropic

NMDA AMPA Kainate

Metabotropic

Class I Class II Class III

mGlu R1 mGlu R1 mGlu R4

mGlu R5 mGlu R3 mGlu R6

mGlu R7

mGlu R8

Glutamatergic systemSynaptic transmission

Glutamatergic systemLocalization of glutamatergic neurons

Cortico: -spinal, -striatic,

-subthalamic, -thalamic, -nigral, -rubral, -

pontinne, -bulbar,

-cortical (commisural)

Hippokampo: -septal, -mamillar

Bulbo: -cortical, -thalamic

Subthalamo: -pallidal, -nigral

Olivo: -cerebellar (climbing fibers)

Cerebellar intrinsic connections: from

granular cells to Purkyne cells

Spino-thalamic

Thalamo: -cortical, -striatic

Glutamatergic systemLearning and memory

Glutamatergic systemLearning and memory

xx

Ions

accumulation

Gene

expression

Glutamatergic systemIschemia in CNS

GABA-ergic system

GABA-ergic systemBasic facts

• increases transmission of Cl-ions to the cell ⇒ induces hyperpolarization

• is the main inhibitory neurotransmiter in brain, spinal cord and retina

• approximately 30-40% neurons synthesize GABA as primary neurotransmiter

GABA-ergic systemSynthesis of GABA

Glutamát

GABA

Glutamát dekarboxyláza

HOOC CH2

CH2

CH COOH

NH2

CO2

HOOC CH2

CH2

CH2 NH

2

GABA-ergic systemReceptors for GABA

HOOC CH2

CH2

CH2 NH

2

Ionotropic

GABAA GABAC

Metabotropic

GABAB

GABA-ergic systemSynaptic transmission

GABA-ergic systemEffect of GABA on membrane potential of neuron depending of maturation

GABA-ergic systemLocalization of GABA-ergic neurons

Striato: -pallidar, -nigral

Pallido: -reticular, -thalamic

Nigro: -tectal, -thalamic

Septo: -hippocampal

Intrinsic: cerebello-nuclear (Purkyne cells -

nuclei)

Intracortical

Intrathalamic

Brain stem

Spinal cord

GABA-ergic systemEpilepsy

Glycinergic system

Glycinergic systemBasic facts

• increases transmission of Cl- ions to the cell - induces hyperpolarization

• inhibitory neurotransmiter of interneurons:

- pons

- medulla

- spinal cord

• inhibitory neurotransmiter of Renshaw neurons in anterior horns of spinal

cord – regulation of spinal reflexes

Glycinerergic systemSynthesis of glycine

Serín

Glycín

Serín transhydroxymetyláza

CO2

HOOC CH2

NH2

HOOC CH COOH

NH2

Glycinergic systemReceptors for glycine

HOOC CH2

NH2

Ionotropic

Glycin R

Glycinerergic systemSynaptic transmission

Glycinergic systemLocalization of glycinergic neurons

Pons

Medulla

Spinal cord (Renshaw neurons)

Acetylcholine and biogenic amines

Neurotransmitters of „slow“ transmission of signalsAcetylcholine and biogenic amines

• Acetylcholine

• Dopamine

• Norepinephrine

• Epinephrine

• Serotonin

• Histamine

Sensory

information

Motor

response

Co

gn

itiv

e p

roc

es

se

s

Cerebral

cortex

ADR

NA

DA

Hist

5-TH

ACh

Neurotransmitters of „slow“ transmission of signalsModulator functions

Central nervous system

Neurotransmitters of „slow“ transmission of signalsModulator functions

Cholinergic system

Cholinergic systemBasic facts

• 1929: izolation of acetylcholine from hourse spleen (Dale and Dudley)

• 1936: proof of acetylcholine synthesis by neurons in CNS (Quastel et al.)

• present in almost all levels of CNS

• approximately 10% of all neurons are cholinergic

• neurotransmiter of all efferent neurons sending their axons from CNS:

- neurotransmiter of motor neurons

- neurotransmiter of preganglionic neurons of autonomic nervous system

- neurotransmiter of postganglionic neurons of parasympathetic system

Cholinergic systemSynthesis of acetylcholine

Acetyl CoA

Cholín

Acetylcholín

Cholín acetyl transferáza

CH2

CH2

CH3

C

O

O N

CH3

CH3

CH3

+

S C

O

CH3

CoA

CH2

CH2

OH N

CH3

CH3

CH3

+

+

CoA

Cholinergic systemReceptors for acetylcholine

CH2

CH2

CH3

C

O

O N

CH3

CH3

CH3

+

Metabotropic

(muscarine)

M1 subtype M2 subtype

M1 M2

M3 M4

M5

Ionotropic

(nicotine)

n ACh

Cholinergic systemSynaptic transmission

Cholinergic systemLocalization of cholinergic neurons

CH 1, 2

CH 3CH 4

CH 5, 6

CH1-3: septum and diagonal region

CH4: ncl. basalis Meynerti

CH5: ncl. pedunculo-pontinus

CH6: ncl. latero-dorsalis

Cholinergic systemCholinergic transmission in PNS

Cholinergic systemFunctions of cholinergic neurons

• attention and sleep

• motivation and reward

• memory and learning

• autonomic functions

• motor functions

• pathological alteration of cholinergic system:

- Alzheimer's disease

- myasthenia gravis

Cholinergic systemNeuro-immune interactions – Cholinergic anti-inflammatory pathway

Tracey, 2007

Tracey, 2007

Cholinergic systemNeuro-immune interactions – Cholinergic anti-inflammatory pathway

Cholinergic systemAlzheimer's disease

Cholinergic systemMastenia gravis

Catecholaminergic system

• Dopaminergic system

• Noradrenalinergic system

• Adrenalinergic system

Catecholaminergic systemSynthesis of dopamine, norepinephrine and epinephrine

OH CH2 CH

NH2

COOH

OH CH2

OH

CH

NH2

OH CH2

OH

CH2

NH2

OH CH

OH

CH2

NH2

OH

OH CH

OH

CH2

NH

OH

CH3

Tyrozín

Dihydroxyfenylalanín (DOPA)

Dopamín

Noradrenalín

Adrenalín

Tyrozínhydroxyláza (TH)

Dekarboxyláza L-aromatických aminokyselín (AADC)

Dopamín-ß-hydroxyláza (DBH)

Fenyletanolamín-N-metyltransferáza (PNMT)

COOH

Dopaminergic system

Dopaminergic systemBasic facts

• 1951: proof of dopamine presence in mammals tissues (Goodall)

• 1959: involvement of dopamine in extrapyramidal functions (A. Carlsson)

• 1962: histofluorescent method of catecholamine and serotonin detection in nervous

tissues (Falc et al.)

• 1975: description of the first dopamine receptor (Seeman)

• 2000 Nobel price: A. Carlsson: A half-century of neurotransmitters research: impact on

neurology and psychiatry

• only approximately 1 from million of neurons is synthesizing dopamine

• the main accumulation of dopaminergic neurons:

- substantia nigra

- area ventralis tegmenti (Tsai)

Dopaminergic systemReceptors for dopamine

OH CH2

OH

CH2

NH2

Metabotropic

D1 group D2 group

D1 D5 D2 D3 D4

D1A D2S

D1B D2L

Dopaminergic systemSynaptic transmission

Dopaminergic systemLocalization of dopaminergic neurons

A8

A10A9

A12

A15

A16

A11A13

A14

A8: ncl. reticularis pontis oralis

A9: substantia nigra, pars compacta

A10: area ventralis tegmenti (Tsai)

A11: ncl. premamillaris dorsalis

A12: ncl. infundibularis (arcuatus)

A13: zona incerta

A14: area hypothalamica anterior

A15: area preoptica

A16: bulbus olfactorius

A17: dopaminergic cells of retina

Dopaminergic systemPathways of dopaminergic neurons

• motivation and reward


• motor functions

• pain

• regulation of secretion of hypothalamo-pituitary system

• pathological alteration of dopaminergic system:

- motor dysfunctions (Parkinson’s disease)

- schizophrenia

- depression

- addiction

- attention deficits

Dopaminergic systemFunctions of dopaminergic neurons

Dopaminergic systemSchizophrenia

Noradrenergic and adrenalinergic system

Noradrenergic and adrenalinergic systemBasic facts

• 1895: description of effects of „active component“ of adrenals (Oliver, Schafer)

• 1897: isolation of epinephrine (Abel, Crawford)

• 1901/1902: isolation of epinephrine in crystal form, description of its structure and

introduction of terms adrenalin/epinephrine (Takamine, Abel)

• 1946: description of norepinehrine (von Euler)

• 1948: discovery of adrenergic receptors (Ahlquist)

• 1970 Nobel price: J. Axelrod: Noradrenaline: fate and control of its biosynthesis

• noradrenergic and adrenalinergic neurons are localized in medulla and pons

• the main structure of the brain synthesizing norepinephrine is the locus coeruleus

• in periphery is norepinephrine and epinephrine synthesized in adrenal medulla and

sympathetic ganglia

Noradrenergic and adrenalinergic systemReceptors for norepinephrine and epinephrine

OH CH

OH

CH2

NH2

OH

OH CH

OH

CH2

NH

OH

CH3

Metabotropic

α1 α2 β1 β2 β3

α1A α2A

α1B α2B

α1D α2C

Noradrenergic systemSynaptic transmission

Noradrenergic systemLocalization of noradrenergic neurons

A1: ncl. reticularis lateralis et

parvocellularis

A2: ncl. tractus solitarii

A4: substantia grisea centralis, pars

caudalis

A5: ncl. reticularis parvocellularis, pars

ventralis

A6: locus coeruleus

A7: ncl. reticularis parvocellularis

A1 A2

A4

A6

A5

A7

C2

C1

C3

C1: ncl. reticularis lateralis et

parvocellularis

C2: ncl. tractus solitarii

C3: ncl. prepesitus hypoglossi

Adrenalinergic systemLocalization of adrenalinergic neurons

Noradrenergic systemPathways of noradrenergic neurons

• alertness and sleep


• motor functions

• stress reaction

• pain


• pathological alteration of noradrenergic system:

- affective disorders

Noradrenergic and adrenalinergic systemFunctions of noradrenergic and adrenalinergic neurons

Noradrenergic and adrenalinergic systemStress response

Noradrenergic and adrenalinergic systemStress response

Noradrenergic and adrenalinergic systemAffective disorders

Noradrenergic and adrenalinergic systemNeuroplasticity and depression

Noradrenergic and adrenalinergic systemAlzheimer's disease

Serotoninergic system

Serotoninergic systemBasic facts

• 1948: isolation of serotonin (Rapport)

• 1953: proof of presence of serotonin in CNS (Twarog, Page)

• 1957: description of the first serotonin receptor

• in brain is approximately 1 million of serotoninergic neurons

• every serotoninergic neuron influences approximately 500 000 neurons

• peripherally is serotonin localized in platelet cells, mast cells and enterochromafine

cells of GIT, do not cross blood-brain-barrier

• serotonin is synthesized from amino acid tryptofan present in food

Serotoninergic systemSynthesis of serotonin

5-Hydroxytryptofán

Serotonín (5-HT)

Dekarboxyláza aromatických L-aminokyselín

CO2

Tryptofán

O2

Tryptofán-5-hydroxyláza

N

OH

H

CH2

CH2 NH

2

N

OH

H

CH2

CH

NH2

COOH

N

H

CH2

CH

NH2

COOH

Serotoninergic systemReceptors for serotonin

N

OH

H

CH2

CH2 NH

2

Ionotropic

5-HT3

Metabotropic

5-HT1 5-HT2 5-HT4 5-HT5 5-HT6 5-HT7

1A 2A 5A

1B 2B 5B

1D 2C

1E

1F

Serotoninergic systemSynaptic transmission

Serotoninergic systemLocalization of serotoninergic neurons

B1: ncl. raphealis palidus

B2: ncl. raphealis parvus

B3: ncl. raphealis magnus

B4: ncl. raphealis palidus

B5: ncl. raphealis pontis

B6: ncl. raphealis dorsalis

B7: ncl. raphealis dorsalis

B8: ncl. cerebralis superior

B9: ncl. reticularis pontis tegmenti

B1B2

B3B4

B5B6

B7

B8B9

Serotoninergic systemPathways of serotoninergic neurons


• pain

• food intake

• sexual behavior

• neurotrophic effects: maturation and development of brain (synaptic plasticity,

length of dendrites, cytoskeleton architecture)

• pathological alteration of serotoninergic system:

- depression

- anxiety

- aggression

Serotoninergic systemFunctions of serotoninergic neurons

Serotoninergic systemAffective disorders

Serotoninergic systemAffective disorders

Serotoninergic systemAffective disorders – alterations of neurogenesis

Serotoninergic systemPain

Histaminergic system

Histaminergic systemBasic facts

• 50’ years of 20. century: study of the effect of antihistaminergic activity of neuroleptics

and antidepressants on behavior

• 2nd half of 70’: description of histaminergic system in the brain

• in CNS are histaminergic neurons localized only in circumscribed region of

hypothalamus

• in periphery is histamine present in mast cells

Histaminergic systemSynthesis of histamine

Histidín

Histamín

Histidín dekarboxyláza

CO2

NNH

CH2

CH2 NH

2

NNH

CH2

NH2

CH COOH

Histaminergic systemReceptors for histamine

NNH

CH2

CH2 NH

2

Metabotropic

H1 H2 H3 H4

Histaminergic systemLocalization of histaminergic neurons

E1: ncl. tuberomamillarisE1

Histaminergic systemPathways of histaminergic neurons


• regulation of body temperature


• pain

• food intake


Histaminergic systemFunctions of histaminergic neurons

Histaminergic systemSleep

Purines

Purines

• adenosine three phosphate – ATP

• adenosine

O

OHOH

CH2

OH

N

N

N

N

NH2

O

OHOH

CH2

OPOPOPH

O O

O O O

O

N

N

N

N

NH2

PurinesReceptors for ATP

O

OHOH

CH2

OPOPOPH

O O

O O O

O

N

N

N

N

NH2

Ionotropic

P2X1 P2X2 P2X3 P2X4 P2X5 P2X6 P2X7

Metabotropic

P2y1 P2y2 P2y4 P2y6 P2y11

PurinesReceptors for adenosine

O

OHOH

CH2

OH

N

N

N

N

NH2

Metabotropic

A1 A2 A3

A2A A2B

ATP:

• central regulation of cardiovascular and respiratory functions (RVLM, pre-Bötzinger

region)

• sensory nerves – transmission of nociceptive information

• autonomic nervous system – transmission between pre- and postganglionic neurons

of sympathetic nervous system

• smooth muscles – excitation

Adenosine:

• sleep and waken

• retrograde synaptic transmission

• mechanisms connecting energy expendure with blood flow in brain

• pathological processes:

- neuroprotective effect during hypoxia and ischemia

- epilepsy – anticonvulsive effect

- addiction – ethanol, opioids

PurinesFunctions of purines in nervous system



PurinesPurines as co-transmitters

Steroid neurotransmitters

Steroid neurotransmittersBasic characterization

• biosynthesis of neurosteroids is present in neurons and glial cells (in cortex and

subcortical areas)

Synthesized by peripheral endocrine glands:

• corticosterone

• aldosterone

• estradiol

• testosterone

Synthesized in periphery and CNS:

• progesterone

• tetrahydroprogesterone, allopregnenolone

Synthesized in CNS:

• dehydroepiandrosterone

Steroid neurotransmittersBasic characterization

Steroid neurotransmittersMechanism of action





• modulation of GABA(A), N-methyl-d-aspartate (NMDA), nicotinic, muscarinic,

serotonin (5-HT(3)), kainate, glycine and sigma receptors

• neuroprotective (17β-estradiol, 3α-reduced pregnane steroids)

• induction of neurite growth, dendritic spines and synaptogenesis

• memory enhancing [pregnenolone, dehydroepiandrosterone (DHEA)]

• sedative (progesterone, 3α-reduced pregnane steroids)

• hypnotic (progesterone, 3α-reduced pregnane steroids)

• anesthetic (progesterone, 3α-reduced pregnane steroids)

• anxiolytic (progesterone, 3α-reduced pregnane steroids)

• sleep modulating (progesterone, 3α-reduced pregnane steroids, pregnenolone,

DHEA)

• anticonvulsant (progesterone, 3α-reduced pregnane steroids)

• antipsychotic (progesterone)

• antidepressant (3α-reduced pregnane steroids)

Steroid neurotransmittersFunctions of steroid neurotransmitters in nervous system

Gaseous neurotransmitters

• NO

• CO

• H2S

• do not fulfill al criteria for classical neurotransmitters

• enable both postsynaptic and presynaptic modulation

• very short biological halftime

Gaseous mediatorsBasic characterization

Gaseous mediatorsNO

Gaseous mediatorsNO

Gaseous mediatorsNO

Gaseous mediatorsNO

Gaseous mediatorsCO

• parakrinne modulation of hypothalamo-pituitary system

• modulation of neurohypophysis functions

• modulation of enteric nervous system functions


Gaseous mediatorsFunctions

Eicosanoids

Eicosanoids

• prostaglandins

• leukotrienes

• thromboxanes

EicosanoidsReceptors for eicosanoids

prostaglandins

Metabotropic

TP IP EP FP DP

TPα TPβ EP1 EP2 EP3 EP4

EP3A EP3B EP3C EP3D

Central nervous system:

• mediators of fever – PGE2

• stimulation of HPA axis – increased secretion of ACTH

• sleep – PGD2 – endogenous inductor of sleep? (released from leptomenings and

plexus choroideus)

Peripheral nervous system:

• inflammatory processes

• pain

• immune reactions

EicosanoidyFunctions of eicosanoids in the nervous system

Other neurotransmitters

Amines:

• tryptamine

• phenyletylamine

• tyramine

• octopamine

• D-serine

• endocanabinoids

Other neurotransmitters

Other neurotransmittersCanabinoids – functions in GIT

Neuropeptides

(neurotransmitters with large molecules)

NeuropeptidesComparison with hormones

• synthesized in body of neurons, where is present necessary synthetic apparatus

(neurotransmitters with small molecule are synthesized in nerve endings),

• are present in tissues in much lower concentrations when compared with classical

neurotransmitters,

• higher frequency of action potentials is necessary for release of neuropeptides from

neuron

• release of neuropeptides and binding on receptors does not evoke fast, but slow effect

on activity and excitability of neurons that continue for longer time (might influence

gene expression in neuron, it might by basis for long-lasting morphological and

functional changes in nervous system)

• can play important role in maturation of nervous system and regeneration of damaged

neurons

NeuropeptidesCharacteristics

NeuropeptidesProcessing

NeuropeptidesSynthesis




neurotransmitters,


neuron

• release of neuropeptides and binding on receptors does not evoke fast, but slow effect

on activity and excitability of neurons that continue for longer time (might influence

gene expression in neuron, it might by basis for long-lasting morphological and

functional changes in nervous system)

• can play important role in maturation of nervous system and regeneration of damaged

neurons

NeuropeptidesCharecteristics

NeuropeptidesRelease




neurotransmitters,


neuron

• release of neuropeptides and binding on receptors does not evoke fast, but slow

effect on activity and excitability of neurons that continue for longer time (might

influence gene expression in neuron, it might by basis for long-lasting morphological

and functional changes in nervous system)

• can play important role in maturation of nervous system and regeneration of

damaged neurons

NeuropeptidesCharecteristics

one neuron = one neurotransmiter

NeuropeptidesColocalization

Main neurotranmiter Co-transmitter

Acetylcholine VIP

substance P

GABA somatostatin

cholecystokinin

Dopamine cholecystokinin

neurotensin

Norepinephrine somatostatin

enkephalin

neuropeptid Y

neurotensin

Serotonin substance P

enkephalin

CRH vasopressin

Neuropeptides

Group NeuropeptideHypothalamic releasing factors CRH: corticotropin releasing hormone

GHRH: growth hormone releasing hormone

GnRH: gonadotropin releasing hormone

Somatostatin

TRH: thyrotropin releasing hormone

Pituitary hormones ACTH: adrenocorticotropic hormone

αMSH: α-melanocyte stimulating hormone

β-endorphin

GH: growth hormone

PRL: prolactin

FSH: follicle stimulating hormone

LH: luteinizing hormone

TSH: thyrotropin [thyroid stimulating hormone]

Neurons only? Galanin

Neuromedin K

NPY: neuropeptide Y

PYY: peptide YY

Opiate peptides β-endorphin

Dynorphin

Leu-enkephalin

Met-enkephalin

GI and brain peptides CCK: cholecystokinin

Gastrin

GRP: gastrin releasing peptide

Motilin

Neurotensin

Substance K; substance P (tachykinins)

Neuronal and endocrine ANF: atrial natriuretic peptide

CGRP: calcitonin gene-related peptide

VIP: vasoactive intestinal peptide

Neurohypophyseal peptides Oxytocin

Vasopressin (Siegel et al., 2006)

NeuropeptidesRegulation of food intake

NeuropeptidesRegulation of food intake

NeuropeptidesClinical applications and trials

Interactions of neurotransmitters systems

Interactions of neurotransmitters systemsStriatum

Interactions of neurotransmitters systemsHistaminergic neurons

Interactions of neurotransmitters systemsAfferent innervation and autoregulation of histaminergic neurons

Interactions of neurotransmitters systemsTransnuclear signalization



Interaction of chemical and electrical synapsesHippocampus

Monographs

• Basic Neurochemistry. Molecular, Cellular and Medical Aspects. Sixth

Edition. Siegel GJ. (Ed.). Lippincott Williams & Wilkins, 2006 (web1 – sixth

edition)

• Neuroscience. Third Edition. Purves, D., Augustine, G.J., Fitzpatrick, D., Hall

WC, LaMantia, AS, McNamara, J.O., Williams, S.M. (Eds). Sinauer Associates,

Sunderland, 2004 (web1 – second edition)

• Neuropsychopharmacology: The Fifth Generation of Progress. Kenneth L.

Davis, Dennis Charney, Joseph T. Coyle, and Charles Nemeroff (Eds.), Lippincott

Williams & Wilkins, Philadelphia, 2002 (web2)

• Neurotransmitters, drugs and brain function. Webster RA (Ed). John

Wiley&Sons, Ltd, Chichester, 2001

• web1: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books

• web2: http://www.acnp.org/modules.php?name=Content&pa=showpage&pid=39

References

• Felten DL, Shetty A. Netter's Atlas of Neuroscience: Saunders, 2009, 464 pp.

• Siegel GJ, Albers RW, Brady ST, Price DL. Basic neurochemistry: Molecular, cellular, and medical

aspects. San Diego: Elsevier Academic Press, 2006, 1016 pp.

• Zoli M, Agnati LF. Wiring and volume transmission in the central nervous system: the concept of closed

and open synapses. Prog Neurobiol 1996; 49: 363-80.

References

Documents

Neurophysiology II - uniba.sk · 2020. 3. 12. · Cholinergic system Basic facts •1929: izolation of acetylcholine from hourse spleen (Dale and Dudley) •1936: proof of acetylcholine