Autonomic (vegetative) nervous system

Prof. Dr. Szabolcs Kéri

University of Szeged, Faculty of Medicine, Department of Physiology

2018

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)

Brainstem nucleiSpinal cord

ANS at glance:

Preganglionic axon

Autonomic ganglion

Postganglionic axon

Visceral effector

organ

Cortex (prefrontal region)

Limbic system(emotions)

Hypothalamus(integrative

role)

Reticularformation

(vital function)

Spinal cord(autonomic

reflexes)

PARASYMPATHETIC 1:Cranial division

Ganglions

PARASYMPATHETIC 2:Sacral division

SYMPATHETIC: Thoracolumbar division

Motor endplate:nerve ending at skeletal muscleNOT 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

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

Visceral afferents

Ggl. spinale

Peripheral nerve

White ramus

Gray ramus

Paravertebralganglion

Prevertebralganglion

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

Tyrosine

Tyrosinehydroxylase

Dihydro-phenyl-alanine (DOPA)

Dopamine-beta-hydroxylase

DOPA-decarboxylase

Norepinephrine

N -methyltransferase

Epinephrine

Dopamine

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)

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

Adrenalin

Medulla

Epinephrine (80%),norepinephrine

Capillary

Chromaffin cells(pheochromocytes)

Preganglionicfibers

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

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

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

Salivatorynuclei

Dorsal motor nucleus of vagus

Nucleusambiguus

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) → glandulasubmandibularis/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)

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

Ganglionicneuron

Early EPSP Late EPSP Peptidergic EPSP/IPSP

VIP, GRP

VIP – Vasoactive Intestinal PolypeptideGRP – Gastrin Releasing Peptide

Postsynaptic action potential

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 apicalmembrane

Parasympathetic:acetylcholine (ACH) and VIP

Choline reuptakeTransporter (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 secretionNO – smooth muscle relaxationATP – smooth muscle contractionGRP – peptidergic EPSP in gangliaEnkephalin – 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