Introduction to the Autonomic Nervous System

1. Introduction to the Autonomic Nervous System George Howell III, Ph.D

2. Nervous system hierarchy Enteric Nervous System

3. Autonomic nervous system • Independent – activities are not under direct conscious control(autonomic = automatic) • Divided into parasympathetic, sympathetic, and sometimes ENS on an anatomical basis • Parasympathetic vs sympathetic divisions • Origin – IML vs CNS nuclei • Ganglia – paravertebral and prevertebralvs ganglia at target organ • Primary neurotransmitters – Ach vs NE

4. Origination of the PNS What’s missing??

6. Synapses of the PNS

7. Synaptic transmission • Synthesis of neurotransmitter from precursors • Action potential spreading depolarization • Activation of VGCa+ channels • Ca+ dependent fusion of neurotransmitter containing vesicles with plasma membrane • Release of transmitters into cleft and binding to postsynaptic receptors • Termination of transmitter action via degradation or reuptake in presynaptic • Activation of postsynaptic cell

8. Major neurotransmitters of the ANS • Acetylcholine (Ach) • Fibers using Ach are cholinergic fibers • Almost all fibers leaving CNS are cholinergic • Major transmitter of preganglionic fibers (sympathetic and parasympathetic) • Major transmitter of parasympathetic postganglionic synapse and Nm junction • Some parasympathetic postganglionics use peptides and NO as modulators • Nicotinic and muscarinic receptors • Norepinephrine (NE) • Fibers using NE are adrenergic fibers • Major transmitter at sympathetic postganglionic synapse • Some sympathetic postganglionics use Ach • Adrenergic receptors • Alpha and beta

9. Other neurotransmitters of the ANS • Dopamine • Modulator in some ganglia and ENS • Sympathetic transmitter in renal blood vessels • Serotonin • Excitatory in ENS • GABA • Inhibitory • Substance P • Sensory neurotransmitter • Excitatory with Ach at Nm junction, vasodilator due to NO release, nociception at peripheral nerve synapses • Vasoactive intestinal peptide • Excitatory secretomotor transmitter in ENS, vasodilator, cardiac stimulant • Adenosine triphosphate (ATP) • Transmitter or cotransmitter at ANS effector synapses • Enkephalins and other endogenous opioids • Inhibitory effect on secretomotor interneurons in ENS, inhibit peristalsis, stimulate secretion • Gastrin releasing peptide (GRP) • Promotes gastrin release from G cells in stomach • Neuropeptide Y • Nitric oxide (NO) • Synthesized on demand by NOS…..not stored • Vasodilation

10. Cholinergic synapse • Synthesis of acetylcholine • Choline is taken up into presynaptic cell by Na+ dependent choline transporter (rate limiting step) • Acetyl CoA + choline = acetylcholine • Catalyzed by choline acetyltransferase • Transported into vesicles by vesicle associated transporter (VAT) • Other cotransmitters are also stored in vesicle • Vesicular release • v-SNAREs (synaptobrevin; subgroup of VAMPs) bind with t-SNAREs (SNAPs; syntaxin and SNAP-25) to mediate vesicular fusion • Ca+ dependent • Blocked by botulinum toxin • Presynaptic and postsynaptic responses to Ach (muscarinic and nicotinic receptors) • Presynaptic receptors – auto and heteroreceptors • Acetylcholinesterase mediated degradation • Acetylcholine to choline + acetate • Terminates action of acetylcholine in cleft

11. Cholinergic receptor subtypes and actions • Nicotinic • Ligand gated Na+ channels • Directly mediate depolarization in excitable cells • Two subtypes: neuronal (Nn) and muscular (Nm) • Muscarinic • GPCRs • 5 subtypes • M1, 3, 5 are coupled to Gq G-proteins • M2, 4 are coupled to Gi G-proteins

12. Role of each cholinoceptor at autonomic ganglia • Nn– milliseconds • Excitatory postsynaptic potential (EPSP) • Temporal or spacial summation leads to AP • M2 – seconds • Inhibitory postsynaptic potential (IPSP) • Follows AP • Mediated by opening of K+ channels • M1 – seconds • Slow EPSP by closing K+ channels • Follows IPSP • Peptides – minutes • Late, slow EPSP • Modulates response of postsynaptic cell to subsequent inputs

13. Adrenergic synapse • Synthesis of NE • Vesicular transport • VMAT • Dopamine converted to NE in vesicle • Neurotransmitter release • Vesicular fusion similar to that of the cholinergic synapse • Neurotransmitter actions • Postsynaptic and presynaptic receptors • Transmitter reuptake • NET and DAT terminate neurotransmitter action

14. Adrenergic receptor subtypes and actions • Alpha • GPCRs • Two subtypes • A1 – Gq protein coupled • A2 – Gi protein coupled • Beta • GPCRs • Three subtypes • B1-3 – Gs protein coupled

15. Autonomic regulation of organ systems

16. Autonomic regulation of cardiovascular function • Baroreceptor reflex • Increase in MAP • Increased baroreceptor firing • Increase parasympathetic tone • Decrease sympathatic tone • Decrease in MAP • Decreased baroreceptor firing • Decrease parasympathetic tone • Increase sympathetic tone

17. Enteric Nervous System • Large and highly organized system of neurons located in the walls of the gastrointestinal system • It is often considered a third division of the autonomic nervous system • Includes the myenteric plexus (of Auerbach) and the submucous plexus (of Meissner)

18. Enteric nervous system Parasympathetic Longitudinal muscle Myenteric plexus Circular muscle layer Submucosal plexus • Walls constricted and sphincters relaxed via M3 • Secretions increased via M3

19. Autonomic regulation of structures associated with the eye Dominant tone = Parasympathetic Iris radial – contracted via alpha-1 Iris circular – contracted via M3 Ciliary muscle – contracted via M3

20. Regulation of the heart Dominant tone = parasympathetic Sympathetic Increases heart rate and contractility via beta-1 and 2 (primarily beta-1) Parasympathetic Decreases heart rate and atrial contractility via M2

21. Regulation of the blood vessels Veins Dominant tone = parasympathetic Arterioles/arteries Dominant tone = sympathetic Contraction via alpha1 Relaxation via beta-2

22. Regulation of the liver • Sympathetic • Increase gluconeogenesis and glycogenolysis • Provide glucose to fuel “flight or fight” response • Primarily beta-2, possibly alpha-1

23. Control of stomach acid • Parasympathetic • Increase histamine release from ECL cell via M3 • Increase H+ production from parietal cell in fundus via M3 • Decrease somatostatin release from D cell in antrum • Increases gastrin release from G cell

24. Regulation of the bladder Parasympathetic • Bladder wall • Constriction via M3 • Relaxation via beta-2 • Sphincter • Relaxation via M3 • Constriction via alpha-1

25. Glandular secretion Sweat Salivary Increased via M3 Appocrine – increased via alpha-1 Eccrine – increased via M Lacrimal gland (tear production) – increased via M

26. Predominant tones of major organ systems • Heart - parasympathetic • Arterioles/arteries - sympathetic • Veins - sympathetic • Iris - parasympathetic • Ciliary muscle - parasympathetic • GI tract (ENS) - parasympathetic • Smooth muscle - parasympathetic • Bladder - parasympathetic • Sweat glands - sympathetic • Salivary glands – parasympathetic • Lacrimal glands – parasympathetic

27. Physiological effects of autonomic innervation and receptors that govern the effect Parasympathetic Sympathetic Contracts the iris radial muscle via alpha-1 Relaxes the ciliary muscle via beta Accelerates the sinoatrial node via beta-1,2 Accelerates ectopic pacemakers via beta-1,2 Increases cardiac contractility via beta-1,2 Relaxes bronchiolar smooth muscle via beta-2 Relaxes GI walls via alpha-2, beta-2 Contracts GI sphincters via alpha-1 Relaxes bladder wall via beta-2 Contracts bladder sphincter via alpha-1 Contracts uterus via alpha, relaxes uterus via beta-2 Contracts pilomotor smooth muscle via alpha Activates sweat glands via alpha, M Increases gluconeogenesis and glycogenolysis in liver via beta-2 and alpha Induces lipolysis via beta-2 Increases renin release from kidney via beta-1 • Contracts the ciliary muscle via M-3 • Decelerates the sinoatrial node via M-2 • Decreases heart contractility via M-2 • Releases EDRF in the endothelium via M-3, M-5 • Contracts bronchiolar smooth muscle via M-3 • Contracts GI walls via M-3 • Relaxes GI sphincters via M-3 • Increases GI secretions via M-3 • Contracts the uterus via M-3 • Causes erection of the penis via M