2019.09.18.

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Autonomic (vegetative) nervous system

Prof. Dr. Szabolcs Kéri

University of Szeged, Faculty of Medicine, Department of Physiology

2019

VEGETATIVE or AUTONOMIC NERVOUS SYSTEM (ANS)

Visceral motor innervation of smooth muscle, cardiac muscle, and glands.

functions:

� homeostasis: constancy of internal environment

� allostasis: change of the internal environment (e.g., adaptation to challenges)

parts:

� sympathetic (energy mobilization)

� parasympathetic (energy conservation)

� enteral (gastrointestinal system motor coordination)

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Brainstem nuclei

Spinal cord

ANS at glance:

Preganglionic

axon

Autonomic ganglion

Postganglionic axon

Visceral

effector

organ

Cortex

(prefrontal region)

Limbic system

(emotions)

Hypothalamus

(integrative

role)

Reticular

formation

(vital

function)

Spinal cord

(autonomic

reflexes)

PARASYMPATHETIC 1:

Cranial division

Ganglions

PARASYMPATHETIC 2:

Sacral division

SYMPATHETIC:

Thoracolumbar division

Motor endplate:

nerve ending at skeletal muscle

NOT A PART of ANS

ANS: visceromotor/secretion system: smooth/cardiac muscle, glands

Skeletomotor system: skeletal muscle

A – epinephrine, NA – norepinephrine, Ach – acetylcholine, N – nicotinic acetylcholine receptor;

M – muscarinic acetylcholine receptor; alpha-beta: adrenergic receptor subtypes; MVV – adrenal medulla

Preganglionic

fibers

Postganglionic

fibers

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Sympathetic nervous system

1. Preganglionic neuron: thoracic – upper lumbar spinal cord, lateral horn

- Preganglionic axons: B fibers (moderately myelinated, 3 μm, 3-15 m/s)

- White ramus (ramus communicans albicans): preganglionic axon → ventral root → paravertebral ganglion (T1-L2)

2. Ganglionic neuron: para-/prevertebral ganglia (ggl. celiacum/mesentericum)

- Postganglionic axons: C fibers (non-myelinated, 0.5-1.5 μm, 0.25-1.5 m/s)

- Gray ramus (ramus communicans griseus): postganglionic axons run to peripheral nerves

Structure of the sympathetic nervous system

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Visceral

afferents

Ggl. spinale

Peripheral

nerve

White ramus

Gray ramus

Paravertebral

ganglion

Prevertebral

ganglion

Postganglionic

fiber

Preganglionic

fiber

Postganglionic

fiber

Lat.

horn

Neurotransmitters: NOREPINEPHRINE, EPINEPHRINE (co-transmitter: neuropeptid Y,

somatostatin)

Release:

- postganglionic terminals (norepinephrine - transmitter)

- adrenal medulla (mainly epinephrine – hormone)

Elimination:

- presynaptic reuptake – monoamine-transporter (Na+-symport)

- metabolism: 1. mitochondria MAO (Monoamine Oxidase)

A – norepinephrine, epinephrine, serotonin

B – dopamine

2. cortex: COMT (Catechol-O-Methyl-Transferase)

endproduct: 3-methoxy-4-hydroxy-phenil-ethylglikol/mandelic acid

Transmitters of the sympathetic nervous system

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Tyrosine

Tyrosine

hydroxylase

Dihydro-

phenyl-

alanine

(DOPA)

Dopamine-beta-

hydroxylase

DOPA-

decarboxylase

Norepinephrine

N -methyltransferase

Epinephrine

Dopamine

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Adrenergic receptors:

α1 (IP3/DAG): postsynaptic (e.g. peripheral vasoconstriction)

α2 (cAMP↓): pre-/postsynaptic (presynaptic autoreceptor, negative feedback)

ß1 (cAMP↑): equal affinity to epinephrine and norepinephrine, mainly

excitatory (e.g. positive cardiac effects)

ß2 (cAMP↑): higher affinity to epinephrine, mainly inhibitory (e.g. peripheral

vasodilatation)

ß3 (cAMP↑): adiposus tissue, striated muscle (thermogenesis)

Cardiovascular:

- Heart: positive chrono-, dromo-, inotropic effect (ß1)

- Blood vessels:

a. mild activation:

norepinephrine – vasoconstriction (α1) = epinephrine – vasodilatation

(ß2) � no changes in total peripheral resistance and blood pressure

b. increased activation:

vasoconstriction > vasodilatation � ↑total peripheral resistance and

blood pressure

Cannon’s alarm reaction (stress reaction)

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Other effects:

- Behavioral and psychological (anxiety, fight or flight) (α1, ß2)

- Motor activity of the gastrointestinal tract↓ (α2)

- Bronchial dilatation (ß2)

- Dilated pupils (α1)

- Piloerection (α1)

Metabolic – energy mobilization:

- Glycogenolysis, gluconeogenesis↑ (α1, ß2)

- Pancreas ß-cell insulin secretion↓ (α2)

- Lipolysis↑(ß3)

The adrenal medulla

Adrenali

n

Medulla

Epinephrine (80%),

norepinephrine

Capillary

Chromaffin

cells

(pheochromocytes)

Preganglionic

fibers

Part of the sympathetic nervous system:

modified ganglion + endocrine gland

Chromaffin cells:

• Pericapillary cells in medulla,

paraganglionic region

• Receiving cholinergic preganglionic

fibers

• Synthesis, storage, and release of

epinephrine (co-transmitter:

neuropeptid Y)

- Epinephrine to target cells via blood

circulation (hormone), degraded by

tissue COMT/MAO-A

- Alarm reaction (Cannon): physical

work, stress, pain, drop in blood

pressure, hypoglycemia

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Non-conventional transmission in the ANS

I. Sympathetic cholinergic innervation: sympathetic postganglionic fibers

innervating sweat glands and their vessels use acetylcholine as a transmitter

II. Non-adrenergic-non-cholinergic transmission: synaptic activity in ANS

independent of acetylcholine and catecholamines

• Independent neurotransmitter: Neuropeptid Y, VIP (Vasoactive Intestinal

Polypeptide), ATP

• VIP + acetylcholine: exocrine glands (↑ secretion/blood flow)

• VIP + NO: relaxation of smooth muscle (e.g. circular smooth muscle in the

gastrointestinal tract)

Parasympathetic nervous system

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Preganglionic neurons:

A. Autonomic nuclei of the brainstem

� Edinger-Westphal (III)

� n. salivatorius superior (VII/V), inferior (IX)

� n. dorsalis nervi vagi (X) (secretomotor)

� n. ambiguus (X) (visceromotor)

B. Sacral region

� Sacral autonomic nucleus

Edinger-

Westphal

Salivatory

nuclei

Dorsal motor

nucleus of vagus

Nucleus

ambiguus

Ganglionic neurons:

I. „Head” ganglia:

1. ggl. ciliare (Edinger-Westphal) � m. sphincter pupillae, m. ciliaris

2. ggl. pterygopalatinum (n. salivatorius superior) � glandula lacrimalis,

nasalis mucosa

3. ggl. submandibulare (n. salivatorius superior) � glandula

submandibularis/sublingualis

4. ggl. oticum (n. salivatorius inferior) � glandula parotidea

II. Ganglia in chest, abdomen, pelvis, proximity/wall of target organs (n. dorsalis nervi vagi, n. ambiguus)

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Transmitter: ACETYLCHOLINE (Ach) (co-transmitter: enkephalin, substance P)

Receptor:

- ganglionic neuron: nicotinic (+M1)

- target organ: muscarinic (M) – inhibited by: atropine

M1 (IP3/DAG): gastric acid↑, exocrine glands↑, brain (memory, attention, M4-5), ganglia

M2 (cAMP↓, K+ channel): heart (negative chrono- és dromotropic effect)

M3 (IP3/DAG, NO↑): smooth muscle (direct effect: contraction, NO-effect: relaxation), glands

Neurotransmission in the parasympathetic nervous system

The synapse between preganglionic fibers and ganglionic neurons

Preganglionic

neuron

Nicotinic

M1Peptide

Ganglionic

neuron

Early EPSP Late EPSP Peptidergic EPSP/IPSP

VIP,

GRP

VIP – Vasoactive Intestinal Polypeptide

GRP – Gastrin Releasing Peptide

Postsynaptic action potential

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Vegetative meshwork: • A network of Schwann-cells in which the terminals

of postganglionic fibers are embedded

• A single fibber innervates thousands of target cells

(en passant synapse)

Varicosities: • Bulbous enlargements of postganglionic fibers

(„strings of beads”) with vesicles and mitochondria

• Inter-varicosities: thin regions linking varicosities

with cytoskeleton

• The transmitter is released from the varicosities

and diffuses to target cells

Synapses of the postganglionic fibers

Vesicle:

acetylcholine

Receptor

ReceptorSmooth

muscle

Contraction

M1/M3

Varicosities

Autonomic innervation of exocrine glands

Phosphorylation

of structural and

regulatory

proteins

ACH

VIP

Enzymes and

mucin secretion

in the ducts

Fusion of granules with the apical

membrane

Parasympathetic:

acetylcholine (ACH) and VIP

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Choline reuptake

Transporter (2)

1. Acetylcholinesterase: degradation of

acetylcholine into acetate and choline in the

synaptic cleft (inhibited by toxic

organophosphates)

2. Choline reuptake (Na+-symport)

3. Acetyl-CoA + choline in presynaptic

terminal (choline-acetyltransferase)

4. Vesicular acetylcholine transporter (H+-

antiport)

Other parasympathetic transmitters:

VIP – vasodilatation, glandular secretion

NO – smooth muscle relaxation

ATP – smooth muscle contraction

GRP – peptidergic EPSP in ganglia

Enkephalin – peptidergic IPSP

Vesicular transzporter

(4)

Cholinergic synapse

Definition: Physiological consequence of spontaneous, low-frequency, baseline activity of

vegetative fibers

(1) Skin and vessels of skeletal muscle: sympathetic tone

- acute spinal shock � blood pressure drop

(2) Heart: parasympathetic tone

• tone is decreased during inspiration � heart rate↑

• denervation: heart rate↑

(3) Gastrointestinal: parasympathetic tone

• tone is decreased during starvation, chronic stress, and in elderly � constipation

Vegetative tone