Prof. Dr. Szabolcs Kéri University of Szeged, Faculty of Medicine, Department of Physiology 2018
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1 Autonomic (vegetative) nervous system Prof. Dr. Szabolcs Kéri University of Szeged, Faculty of Medicine, Department of Physiology 2018
2 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)
3 ANS at glance: Cortex (prefrontal region) Limbic system (emotions) Hypothalamus (integrative role) Reticular formation (vital function) Spinal cord (autonomic reflexes) Brainstem nuclei Spinal cord Autonomic ganglion Preganglionic axon Postganglionic axon Visceral effector organ
4 ANS: visceromotor/secretion system: smooth/cardiac muscle, glands Skeletomotor system: skeletal muscle Preganglionic fibers Ganglions Postganglionic fibers PARASYMPATHETIC 1: Cranial division SYMPATHETIC: Thoracolumbar division Motor endplate: nerve ending at skeletal muscle NOT A PART of ANS PARASYMPATHETIC 2: Sacral division A epinephrine, NA norepinephrine, Ach acetylcholine, N nicotinic acetylcholine receptor; M muscarinic acetylcholine receptor; alpha-beta: adrenergic receptor subtypes; MVV adrenal medulla
5 Sympathetic nervous system
6 Structure of the 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, μm, m/s) - Gray ramus (ramus communicans griseus): postganglionic axons run to peripheral nerves
7 Visceral afferents Ggl. spinale Lat. horn Peripheral nerve Preganglionic fiber Postganglionic fiber Postganglionic fiber Prevertebral ganglion White ramus Gray ramus Paravertebral ganglion
8 Transmitters of the sympathetic nervous system 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
9 Tyrosine Norepinephrine Dihydrophenylalanine (DOPA) Tyrosine hydroxylase Dopamine-betahydroxylase DOPAdecarboxylase N -methyltransferase Epinephrine Dopamine
10
11 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)
12 Cardiovascular: Cannon s alarm reaction (stress reaction) - 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
13 Metabolic energy mobilization: - Glycogenolysis, gluconeogenesis (α1, ß2) - Pancreas ß-cell insulin secretion (α2) - Lipolysis (ß3) 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)
14 The adrenal medulla Part of the sympathetic nervous system: modified ganglion + endocrine gland Medulla Adrenali n Epinephrine (80%), norepinephrine Chromaffin cells: Pericapillary cells in medulla, paraganglionic region Receiving cholinergic preganglionic fibers Synthesis, storage, and release of epinephrine (co-transmitter: neuropeptid Y) Preganglionic fibers Chromaffin cells (pheochromocytes) Capillary - 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
15 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)
16 Parasympathetic nervous system
17 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) Edinger- Westphal B. Sacral region Sacral autonomic nucleus Salivatory nuclei Dorsal motor nucleus of vagus Nucleus ambiguus
18 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)
19 Neurotransmission in the parasympathetic nervous system 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
20 The synapse between preganglionic fibers and ganglionic neurons Preganglionic neuron Nicotinic M1 Peptide VIP, GRP Ganglionic neuron Early EPSP Late EPSP Peptidergic EPSP/IPSP Postsynaptic action potential VIP Vasoactive Intestinal Polypeptide GRP Gastrin Releasing Peptide
21 Synapses of the postganglionic fibers Vesicle: acetylcholine Smooth muscle Varicosities M1/M3 Receptor Contraction Receptor 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
22 Autonomic innervation of exocrine glands Parasympathetic: acetylcholine (ACH) and VIP Enzymes and mucin secretion in the ducts VIP Phosphorylation of structural and regulatory proteins ACH Fusion of granules with the apical membrane
23 Vesicular transzporter (4) Choline reuptake Transporter (2) Cholinergic synapse 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
24 Vegetative tone 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
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