This is a 23 slide presentation introducing the key facts about the autonomic nervous system (ANS), It is suitable for intermediate level learners.

1. Introduction to the Autonomic
Nervous System
Professor John A. Peters
E-mail j.a.peters@dundee.ac.uk
“The autonomic nervous system consists of nerve cells and nerve fibres, by means of
which efferent impulses pass to tissues other than multi-nuclear striated muscle” [John
Newport Langley in his classic text ‘The Autonomic Nervous System’ (1921)]. He was
also a pioneer of the receptor theory, postulating the existence of ‘receptive substances’
as early as 1905.
John Newport Langley
Neuroeffector junctions between a
postganglionic fibre (N) and
intestinal smooth muscle cells (S)
(Burnstock, 1988)
N
S
3 μm

2. Learning Objectives
Following this lecture and further study students should be able to:
 Appreciate that the autonomic nervous system (ANS) is essential to life due its
fundamental roles in homeostasis
 Describe the anatomy of the motor ANS utilizing the terms, pre- and post-ganglionic
fibre, ganglia, paravertebral ganglia and prevertebral ganglia
 Name the ‘classical’ neurotransmitters synthesised and released by pre- and post-
ganglionic fibres in the sympathetic and parasympathetic divisions of the ANS and the
receptors that they act upon understanding the meaning of the terms cholinergic,
cholinoceptor, adrenergic, adrenoceptor and non-adrenergic , non-cholinergic (NANC)
 State the effect of sympathetic and parasympathetic stimulation upon selected targets
noting their frequently reciprocal, but in some instances unopposed, effects
 Provide a simple description of neurochemical transmission in the sympathetic and
parasympathetic divisions of the ANS noting subtypes of cholinoceptor, adrenoceptor,
their exemplar organ distribution and physiological actions
Recommended reading:
• Boron WF, Boulpaep EL (2017). ‘Medical Physiology’ (3rd. ed.). Chapter 14, pp. 334 –
347.
• Naish J, Syndercombe Court D (2014). ‘Medical Sciences’ (2nd. ed.). Chapter 4, pp.
125 - 130 and 138 - 147.
• Koeppen BM, and Stanton BA (2018). ‘Berne and Levy Physiology’ (7th. ed.). Chapter
11.
• Neal MJ (2016). ‘Medical Pharmacology at a Glance’ (8th. ed.). Chapter 7.
• Rang HP, Ritter JM, Flower RJ, Henderson G (2016). ‘Rang and Dale’s Pharmacology’
(8th. ed.). Chapter 12.

3. Introduction to the Autonomic Nervous System
 The entire nervous system can be divided broadly into the Central Nervous
System (CNS) and Peripheral Nervous System (PNS) and their subdivisions.
The Autonomic Nervous System (ANS) has both central and peripheral
components
PNS
CNS (Brain and Spinal Cord)
Somatic afferent
(i.e. sensory fibres, from
skin and skeletal muscle)
Somatic efferent
(i.e. motor fibres to
skeletal muscle)
Enteric
(ENS)
Sympathetic
division
Parasympathetic
division
Afferent signals
(towards the
CNS)
Efferent signals
(away from the
CNS)
Autonomic (ANS)
(motor and sensory
components)

4. The Overall Functions of the ANS
The motor autonomic nervous system (ANS) mediates output from the
CNS to the whole of the body, with the exception of skeletal (voluntary)
muscle. Output is modulated by external and internal sensory input, often
via reflexes involving negative feedback loops within PNS and the CNS
• contraction and relaxation of vascular and visceral smooth muscle
• the heartbeat (including rate and force)
• all exocrine and certain endocrine secretions
• aspects of metabolism (particularly in liver and skeletal muscle)
• modulation of the processes of the immune system
• is subdivided anatomically into sympathetic and parasympathetic
divisions (and, debatably, the enteric nervous system also)
 regulates functions essential to human health and life that do not
require conscious effort (e.g. whilst asleep) and that are largely
involuntary, e.g.
The ANS:
 training allows a degree of conscious influence over the execution of some
ANS reflexes (e.g., micturition, defecation via voluntary control of skeletal muscle
external sphincters of the urethra and anus commanded by somatic efferents).
Uniquely, accommodation in the eye (focus of the lens, for near vision) can be
voluntarily controlled, despite it being an autonomic function

5.  Sympathetic and parasympathetic divisions of the ANS often work
simultaneously in a reciprocal and complementary manner maintaining
homeostasis
Basic Organisation of the Motor ANS (1)
Inside
CNS
Autonomic
ganglion
Preganglionic
neurone
Postganglionic
neurone
Effectorcells
Chemical synaptic
transmission in the
ganglia
e.g.,cardiac’
smoothmuscle,or
secretorycells
Outside CNS
Chemical transmission
at the neuroeffector
junction
 The motor (efferent) component comprises two neurones in series:
preganglionic and postganglionic fibres
Parasympathetic ANS
• regulates many functions, some
of which are restorative and
energy conserving ‘rest and
digest’
Sympathetic ANS
• orchestrates the stress response and
energy consumption associated with
‘fight or flight’ reactions, but also has
very important ongoing activity
 ‘Fight or flight’ and ‘rest and digest’, although memorable, are simplistic
descriptions of the extremes of sympathetic and parasympathetic activity

6. Basic Organisation of the Motor ANS (2)
The transmitter of the preganglionic neurones, sympathetic and parasympathetic,
is always acetylcholine (ACh) acting via excitatory nicotinic cholinoceptors, but
the classical transmitters of the postganglionic neurones are different [i.e.
noradrenaline (NA), aka norepinephrine (NE)] and ACh, respectively
Thoracolumbaroutflow
fromspinalcord
Preganglionic neurone (cholinergic,
synthesises and releases ACh as
transmitter)
Postganglionic neurone (usually
adrenergic, synthesises and
releases NA as transmitter)
Sympathetic division
acetylcholine (ACh) usually noradrenaline (NA)
Effectorcells
(actionvia
adrenoceptors)
Craniosacraloutflow
frombrainstemandspinal
cord
Preganglionic
neurone (cholinergic)
Postganglionic
neurone (cholinergic)
Parasympathetic division Acetylcholine
(ACh)
Effectorcells
(actionviamuscarinic
cholinocepors)

7. Basic Organisation of the Motor ANS (3)
 Sympathetic preganglionic neurones synapse with postganglionic neurones in
either (i) paravertebral ganglia, or (ii) prevertebral ganglia (see next slide), both
of which are close to the spinal cord. Their axons (fibres) are typically short
 Sympathetic postganglionic neurones innervate effector cells in organs distant
to the sympathetic ganglia. Their axons (fibres) are generally long
 Parasympathetic preganglionic neurones synapse with postganglionic
neurones in terminal ganglia that are distant to the CNS and often located in
the walls of the target organ. Their axons (fibres) are thus long.
Correspondingly, the fibres of the postganglionic neurones are short
 Typically, preganglionic fibres, both sympathetic and parasympathetic are
myelinated (see lecture upon the action potential) and are termed motor B-
fibres. They give a white appearance. By contrast, postganglionic fibres are
largely unmyelinated and appear grey and are termed motor C-fibres
 Sympathetic preganglionic fibres branch extensively to synapse with many
postganglionic neurones located in one, or several, pre- or para-vertebral
ganglia. The effect of sympathetic stimulation may sometimes be widespread
(as in the ‘fight or flight’ reaction)

8. Postganglionic neurone
– usually releases NA
L2, or L3, spinal
nerve
Thoraco-
lumbar
outflow
Sympathetic chain
Paravertebral ganglia:
pre- and post-ganglionic
neurones synapse here at
segmental, or more
rostral/caudal locations
T1 spinal nerve
The Sympathetic Outflow (1)
Preganglionic neurone
– releases ACh: note the
‘anatomical logic’ of the
segment of the cord at
which the preganglionic
neurone cell bodies are
located in relation to the
location of the target
tissue/organ
Prevertebral ganglia:
pre- and post-ganglionic
neurones synapse here
Adrenal gland – note the
innervation is pre
ganglionic and the
transmitter is ACh, not NA.
The medulla of the gland
releases adrenaline (A) and
NA as hormones
Higher centres in the
brainstem regulate
sympathetic outflow
Cervical ganglia
(superior, middle
and inferior)
1
2
3
1, coeliac; 2,
aorticorticorenal, 3,
superior mesenteric and 4,
inferior mesenteric
prevertebral ganglia
Modified from Moore’s
Clinically Oriented
Anatomy (2006)
4

9. The Sympathetic Outflow (2) – further anatomical features
 Preganglionic fibre cell bodies are located in the intermediolateral (IML) cell
column (lateral horn) of the spinal cord. Those controlling a particular organ
(e.g. the heart) may be spread over several segmental levels
 Preganglionic fibres exit the cord
via the ventral (anterior) roots,
follow the spinal nerves and white
rami communicantes (at levels T1
to L2/3) and then synapse with
postganglionic cell bodies in
either:
• paravertebral sympathetic
ganglia, from which the
postganglionic fibres join the
peripheral nerves, via grey
rami communicantes, to travel
to their target organs in the
skin and blood vessels
or
• prevertebral sympathetic
ganglia of the abdomen via
paravertebral ganglia (without
synapsing), and onwards in
splanchnic nerves to internal
organs/vessels From Koeppen and Stanton (2018)

10.  Postganglionic fibres (sudomotor neurones) innervating the
thermoregulatory (eccrine) sweat glands, and a few blood vessels are
cholinergic: thus the transmitter is ACh, not NA. Correspondingly, the
receptors on the effector cells are muscarinic cholinoceptors, not
adrenoceptors. However, the postganglionic fibres innervating the stress
(apocrine) sweat glands are adrenergic and activate adrenoceptors
 Preganglionic fibres also innervate neurones in the pelvic plexuses
 Additional to the classical transmitter, NA, postganglionic fibres store and
release others [e.g. adenosine triphosphate (ATP) and neuropeptide Y (NPY)
(see later)]
The Sympathetic Outflow (3) – additions and exceptions to the
general rules
 Preganglionic cholinergic fibres
innervate the adrenal medulla,
chromaffin cells specifically,
directly via splanchnic nerves.
• Chromaffin cells are modified
postganglionic neurones that
secrete, primarily adrenaline (80%),
but also NA (20%) that enter the
capillary circulation as hormones

11. Cranial nerves (CN) III,
VII, IX & X X
The Parasympathetic
Outflow (1)
Preganglionic neurone
– releases ACh
Postganglionic neurone
– releases ACh
Parasympathetic are usually
in the target organs (discrete
ganglia in head and neck and
some plexuses in the pelvis)
IX
VII
III
Sacral spinal nerves
(S2-S4)
Modified from Moore’s
Clinically Oriented
Anatomy (2006)

12. Origin and CN Ganglion Postganglionic fibre target
Midbrain
CN III (oculomotor)
Ciliary Eye (pupillary constrictor and ciliary body)
Pons
CN VII (facial)
Pterygopalatine
Submandibular
Lacrimal gland, glands of nasal cavity
Submandibular and sublingual salivary glands
Medulla oblongata
CN IX (glossopharyngeal)
CN X (vagus)
Otic
Widespread, diffuse
Parotid salivary glands
Bronchial tree, heart, liver, pancreas, upper G.I. tract
 Preganglionic fibres of the sacral outflow course in the sacral nerves (nervi
erigentes) synapsing upon postganglionic neurones in the walls of visceral
organs in the abdominal and pelvic cavities
 Preganglionic fibre cell bodies are located in:
• the brainstem (cranial outflow) comprising the
midbrain, pons and medulla oblongata
or
• sacral segments (S2-S4) of the spinal cord
The Parasympathetic Outflow (2) – further anatomical
features and additions
 Preganglionic fibres of the cranial outflow follow
cranial nerves (CN) and synapse upon postganglionic
neurones as tabulated below:
 Additional to the classical transmitter, ACh, postganglionic fibres release
others [e.g. nitric oxide (NO) and vasoactive intestinal peptide (VIP) (see later)]

13. Chemical Transmission in the ANS (1)
Sympathetic division
Ca2+ Ca2+
Effectorcell
 noradrenaline activates G-protein-coupled adrenoceptors in the effector
cell membrane to cause a cellular response via ion channels/enzymes
 ACh binds to and opens ligand-gated ion channels (nicotinic ACh receptors) in
the postganglionic neurone, causing depolarization and the initiation of action
potentials that propagate to the presynaptic terminal of the neurone, triggering
Ca2+ entry and the release, usually, of noradrenaline
Action potential originating in the CNS
 travels to the presynaptic terminal of the preganglionic neurone triggering Ca2+
entry through voltage-gated, calcium selective, ion channels and the release of
ACh by exocytosis

14. Chemical Transmission in the ANS (2)
Parasympathetic division
Ca2+
Effectorcell
Ca2+
Ca2+
The process is very similar to that described for the sympathetic division, with
the important exceptions that:
ACh activates G-protein- coupled muscarinic acetylcholine receptors
in the effector cell membrane to cause a cellular response via ion channels/
enzymes
ACh is always the classical transmitter used by postganglionic neurones

15. Chemical Transmission in the ANS (3)
 ACh and NA are not the only transmitters released from sympathetic
and parasympathetic postganglionic fibres
• in some instances, the transmitter is neither NA, nor ACh, which is known
as non-adrenergic, non-cholinergic (NANC) transmission
• far more frequently, NA or ACh are co-released with a NANC co-transmitter
(or modulator), the best studied substances being:
o adenosine triphosphate (ATP) and neuropeptide Y (NPY) from
sympathetic fibres
o nitric oxide (NO) and vasoactive intestinal peptide (VIP) from
parasympathetic fibres
Parasympathetic Sympathetic
Rapid response
Intermediate response
Slow response
Tissue response
ACh
NO
VIP
ATP
NA
NPY

16. Tensionofvascular
smoothmuscle
Time
An Example of Chemical Co-Transmission in the ANS –
regulation of vascular smooth muscle tone
Electrical stimulation of postganglionic
sympathetic fibre to vessel
1 2 3 1. ATP produces a fast
contraction of the smooth
muscle
2. Noradrenaline produces a
moderately fast response
3. Neuropeptide Y produces a
slow response
Tensionofvascular
smoothmuscle
Time
Electrical stimulation of postganglionic
parasympathetic fibre to vessel
1 2
1. Acetylcholine and nitric
oxide produce a rapid
relaxation
2. Vasoactive intestinal
peptide can produce a
slow, delayed response
Based on Boron and Boulpaep (2017)

17. Classical Receptor Classes of the Ganglia and
Effector Cells (Cholinoceptors)
 ACh is the endogenous agonist of cholinoceptors that are nicotinic, or
muscarinic
• Nicotinic ACh receptors of the ganglia are:
o Ligand-gated ion channels (LGICs),
selectively activated by the plant alkaloid,
nicotine
o Structurally and pharmacologically distinct
from nicotinic receptors at the skeletal
neuromuscular junction, or in the CNS
Tobacco plant
Nicotiana tabacum
• Muscarinic ACh receptors of the effector
cells are:
o G-protein-coupled receptors (GPCRs),
selectively activated by the plant alkaloid,
muscarine
o Structurally and pharmacologically defined
as five subtypes: M1, M2, M3, M4 and M5 that
are differentially expressed across
tissues/organs, M1-3 being most important
in the ANS
Fly Agaric
Amanita muscaria

18.  NA and adrenaline (A) are the endogenous agonists of a family of
adrenoceptors that are all GPCRs:
o Fundamentally classified, originally on the basis of the rank order of
potency of agonists (Ahlquist, 1948), as α-, or β-adrenoceptors
• α-adrenoceptor: noradrenaline > adrenaline > isoprenaline (for α1 – see below)
• β-adrenoceptor: isoprenaline > adrenaline > noradrenaline (for β2 - see below)
Classical Receptor Classes of the Ganglia and
Effector Cells (Adrenoceptors)
o Clinically important subclasses of adrenoceptors, with differing tissue
locations, have been characterised structurally and pharmacologically as
α1, α2, β1, β2 and β3, all of which are selectively targeted by current
therapeutic agents
• α1- and α2-adrenoceptors are further characterised as α1A, α1B, α1D, α2A, α2B and
α2C. It is not essential to elaborate upon this here!
Noradrenalineaka
norepinephrine
Adrenalineaka
epinephrine
Isoprenalineaka
isoprotorenol
CH3
CH3
CH3
Isoprenaline is
a synthetic
agonist

19. Selected Activities of the ANS
Decreases heart rate (M2) and force
(M2) in atria
Increases heart rate (β1)
Increases force of contraction
in atria and ventricles (β1)
Sympathetic stimulation (via
adrenoceptors, mostly)
Constricts bronchi (M3)
Stimulates mucus production (M3)
(airway resistance)
Relaxes bronchi (β2)
Decreases mucus production (β2)
(airway resistance)
Parasympathetic stimulation
(via muscarinic cholinoceptors, mostly)
No effectRelease of adrenaline from adrenal
medulla (nicotinic AChR)
Increases intestinal motility and
secretions (M3)
Relaxes sphincters (NO, M3)
Reduces intestinal motility (α1, α2, β2)
Constricts sphincters (α1, α2, β2)
Constricts vasculature in most
locations (α1), but relaxes in skeletal
muscle (β2)
Largely no effect, but relaxes
vasculature in a few locations (e.g.
penis, salivary glands, pancreas (NO,
M3)
Ejaculation (α1) Penile erection (NO, M3)
Relaxes wall (detrusor) of
bladder (β2/β3), constricts
internal urethral sphincter (α1)
Contracts wall of bladder (M3),
relaxes internal urethral sphincter
(NO)

20. An Example of the Co-ordinated Activity of the Sympathetic and
Parasympathetic Divisions of the ANS – the Micturition Reflex
 The urinary bladder is a temporary store for urine, until it is convenient to void.
At a simple level, it comprises: (i) a smooth muscle wall (the detrusor) and (ii) a
trigone where urine enters from the ureters and leaves via the smooth muscle
internal urethral sphincter (at the junction between the bladder and urethra)
 During filling, sympathetic activity
predominates:
• the detrusor is relaxed by the release of
NA (NE) that activates β2/β3-adrenoceptors
• the internal urethral sphincter is
constricted by the release of NA that
activates α1-adrenoceptors
 During voiding, parasympathetic
activity predominates:
• the detrusor is contracted by the
release of ACh that activates M3-
muscarinic ACh receptors
• the internal urinary sphincter is relaxed
by the release of NO that stimulates the
production of cGMP (a relaxant) in
smooth muscle cells
 With training, voluntary control is exerted by somatic efferents that release
ACh to contract the skeletal muscle external urethral sphincter surrounding
the urethra via nicotinic ACh receptors
From Hill, WG (2015). Clin J Am Soc
Nephrol, 10, 480-492

21. Common Misconceptions Regarding the ANS (1)
 The phrases ‘fight, or flight’ and ‘rest and digest’ foster the idea that
sympathetic activity is predominantly short-lived (i.e. phasic) whilst
parasympathetic activity is largely ongoing (i.e. tonic’). However,
‘‘…this whole concept is simply wrong.’’ (Gibbins, 2013). Phasic and
tonic activity is common in both divisions of the ANS (see next slide)
 The sympathetic and parasympathetic divisions are activated ‘en
masse’. This is untrue, the activity of the autonomic output to
individual organs and tissues is closely adjusted to match
physiological demand which, or course, varies with the external and
internal environments over time
 The two divisions of the ANS are in opposition to each other. ‘‘This
quite the wrong idea. Autonomic nerves, whatever their anatomical
origin, act in concert to control visceral organs and the vasculature.’’
(Furness, 2006)

22. Tonic and phasic activity in autonomic pathways
Tonic activity Phasic activity
Sympathetic
Skin vasoconstriction
Muscle vasoconstriction
Gut vasoconstriction
Inhibition of gut motility
Inhibition of gut secretions
Detrusor relaxation
Internal urethral sphincter contraction
Sweating (thermal and stress)
Piloerection
Increased cardiac output
Mucous saliva production
Pupil dilation
Sexual activity (ejaculation)
Parasympathetic
Reduced cardiac output at rest
Pupil constriction
Basal tear secretion
Basal saliva secretion
Accommodation
Tear production in crying
Salivation (during speech, eating)
Receptive relaxation and emptying of stomach
Pancreatic secretion
Urination
Sexual activity (erection)
Common Misconceptions Regarding the ANS (2)
Table adapted from Gibbins (2013)
Now test yourself by trying from the information provided in
this and the following lecture and recommended reading to
identify the subtypes of receptor that mediate the above
tonic and phasic activities of the ANS

23. Consolidation of the Fundamentals of the ANS
 Has central and peripheral components. The motor (efferent) component
conducts signals to the entire body, apart from skeletal muscle
The ANS:
 Regulates essential physiological functions, helping to maintain homeostasis
via complementary actions of its sympathetic and parasympathetic divisions
 The motor component comprises cholinergic preganglionic neurones with a
sympathetic thoracolumbar origin, or a parasympathetic craniosacral origin
 In the sympathetic division, preganglionic fibres synapse upon usually
adrenergic postganglionic neurones in either paravertebral, or prevertebral,
ganglia
 In the parasympathetic division, preganglionic fibres synapse upon
cholinergic postganglionic neurones in effector organs, or close to them
 Cholinergic fibres release ACh as transmitter that activates cholinoceptors
that are either (i) ligand-gated ion channels (nicotinic), or (ii) G-protein-
coupled receptors (GPCRs, muscarinic)
 Adrenergic fibres release NA as transmitter that activates adrenoceptors, all
of which (α and β) are G-protein-coupled receptors
 In addition to the classical transmitters (ACh and NA), co-transmitters (e.g.
ATP, NPY, NO and VIP) also regulate the activity of target organs
facts