Introduction to the Autonomic Nervous System

George Howell III, Ph.D

Nervous system hierarchy

Enteric Nervous System

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 prevertebral vs ganglia

at target organ– Primary neurotransmitters – Ach vs NE

Origination of the PNSWhat’s missing??

Synapses of the PNS

Synaptic transmission

1. Synthesis of neurotransmitter from precursors

2. Action potential spreading depolarization

3. Activation of VGCa+ channels4. Ca+ dependent fusion of

neurotransmitter containing vesicles with plasma membrane

5. Release of transmitters into cleft and binding to postsynaptic receptors

6. Termination of transmitter action via degradation or reuptake in presynaptic

7. Activation of postsynaptic cell

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

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

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

Cholinergic receptor subtypes and actionsNicotinic

• 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

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

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

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

Autonomic regulation of organ systems

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

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)

Enteric nervous system

Myenteric plexus

Submucosal plexus

Longitudinal muscle

Circular muscle layer

Parasympathetic

• Walls constricted and sphincters relaxed via M3

• Secretions increased via M3

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

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

Regulation of the blood vessels

Veins

Dominant tone = parasympathetic

Arterioles/arteries

Dominant tone = sympathetic

Contraction via alpha1

Relaxation via beta-2

Regulation of the liver

• Sympathetic– Increase gluconeogenesis and glycogenolysis– Provide glucose to fuel “flight or fight” response– Primarily beta-2, possibly alpha-1

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

Regulation of the bladder

Parasympathetic

• Bladder wall– Constriction via M3– Relaxation via beta-2

• Sphincter– Relaxation via M3– Constriction via alpha-

1

Glandular secretionSweat

Salivary

Appocrine – increased via alpha-1Eccrine – increased via M

Increased via M3

Lacrimal gland (tear production) – increased via M

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

Physiological effects of autonomic innervation and receptors that govern the effect

Parasympathetic Sympathetic• 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

• 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