Autonomic Nervous system

Gregory Conductier (Room FG12, 13F):

gregory.conductier@monash.edu

References:
Autonomic nerves, Wilson-Pauwels, Stewart, Akesson (1997).
http://what-when-how.com/neuroscience/
Autonomic nervous system: Autonomic
Functions
Summary of the previous episode
SOME of these functions include the regulation of:
- homeostasis
- heart rate and blood pressure (acutely)
- respiratory drive and lung volume
- smooth muscle contraction (gastrointestinal motility,
throughout body)
- pupil diameter
- piloerection
- sweating
- urination
- sex organs function
 Autonomic nervous system
Summary of the previous episode

Sympathetic Parasympathetic

Preganglionic neuron: Preganglionic neuron:

- short axons - long axon
- soma in the lateral horn (IML, - soma in the brainstem
T1-L2) - exit the brainstem via cranial nerves 3,
- exit the spinal cord via the 7, 9 and 10
ventral root - soma in the sacral lateral horn of the
- myelinated cord
- viscerotopy - exit the spinal cord via pelvic nerves
- project to para/prevertebral (ventral root)
ganglion - low divergence
- could form splanchnic nerves - cholinergic
- some project to the adrenal - acts on nicotinic receptors
medulla
Postganglionic
- divergence neuron: Parasympathetic postganglionic
-- longer axons
cholinergic neuron:
-- soma
acts oninnicotinic
the sympathetic
receptor ganglion - shorter axons
- low myelination - soma in the parasympathetic
- reach the target organ through nerves ganglion (head) or
- acetylcholine nicotinic receptors - within the target organ
- Noradrenergic (excep for the sweat - cholinergic
gland: Ach) - acts on muscarinic receptors
 Autonomic nervous system
Summary of the previous episode
Sympatheti Parasympath
c etic

Preganglionic
ACh = acetylcholine

nAChR = Nicotinic acetylcholine

Receptors
mAChR = muscarinic acetylcholine
Receptors
NA = Noradrenaline
ACh
nAChR -AR = -Adrenergic receptors

-AR = -Adrenergic Receptors

Postganglionic

NA ACh
-AR -AR mAChR
Effector (target)

The communication between postganglioninic fibres and the target cells involves
neuroeffector junctions
 Autonomic nervous system
The neuro-effector junction

Axon of postganglionic
autonomic neuron

Smooth muscle
Varicosities cells

Postganglionic axons ends with a series of swollen areas contacting the

target called varicosity
 Autonomic nervous system
The neuro-effector junction

Vesicle containing
neurotransmitter
Axon of postganglionic
autonomic neuron

(From Wilson-Pauwels et al., 1997)

Smooth muscle
Varicosities cells

Neurotransmitter is released into the interstitial fluid and diffuses to wherever

the receptors are located. This results in less directed (more widespread)
 Sympathetic nervous system
Noradrenaline: Synthesis, removal and receptors

Varicosity
Metabolised
Tyrosine Dopa DA Postganglionic neuron

Diffusion to blood
Ca2+ Metabolised
Post-junctional element
Metabolised

Dopamine (DA) Pre-junctional NA reuptake transporter (cocaine)

1-adrenergic receptor

Vesicular transporter Post-junctional NA transporter (corticol)

-adrenergic receptor
Monoamine oxidase (MAO)
Noradrenaline
2-adrenergic receptor
Catechol-O-methyl transferase (COMT)
Voltage-gated Calcium channel
 Sympathetic nervous system
Noradrenaline: Synthesis, removal and receptors
Receptors Found in G protein coupling Effect of target tissue

1 Most sympathetic targets Gq (activates PLC) Contraction / constriction

Eyes Mydriasis and far vision
Arteries smooth muscles Vasoconstriction (increase blood pressure

2 GI tract and pancreas Gi/G0 (inhibits AC) Decrease secretion

Pre-junctional varicosity Gi/G0 (inhibits AC) Inhibits NA release

1 Heart, kidney Gs (activates AC) Increase contraction strength and rate

2 Some smooth muscles Gs (activates AC) Relaxation of sphincters

Dilatation airway (relaxation)

Some blood vessels Dilatation of veins (relaxation)

Pancreatic -cells Increase secretion

3 Adipose tissue Gs (activates AC) Increase lipolysis

Overall, activation of the sympathetic system prepare the organism for the
fight or flight response through activation of the different NA receptors
populations
 Sympathetic nervous system
Noradrenaline: Synthesis, removal and receptors:
the summary

Varicosity
Metabolised
Tyrosine Dopa DA Postganglionic neuron

Diffusion to blood
Ca2+ Metabolised
Post-junctional element
Noradrenaline:
- Synthetized and stored in the vesicles of the varicosities
- Many receptors: different actions
- Presynaptic 2 NA receptors: inhibition of NA release
- Multiple removal processes:
- Reuptake into the pre-junctional element and recycling
- Uptake by surrounding cells
- Catechol-O methyl transferase (COMT)
- Monoamine oxidase (MAO)
- Diffusion
 Sympathetic nervous system
Non classical sympathetic transmitter: ATP

Varicosity

Ca2+

Post-junctional element
ATP
Noradrenaline

-adrenergic receptor

Purinergic receptors:
P1: adenosine receptor, GPCR
P2X: ATP receptor, Ionotropic
P2Y: ATP receptors, GPCR
 Sympathetic nervous system
Non classical sympathetic transmitter: ATP
Vas deferens: storage of mature sperm and emission into urethra

A B
contraction

no drug

A + -adrenoceptor blocking drug

B + purinoceptor blocking drug (P2X receptor)

P2X receptor -/- mice: infertile

 Sympathetic nervous system
Non classical sympathetic transmitter: ATP

Varicosity

Ca2+

Post-junctional element
ATP
ATP:
Noradrenaline
- In vesicles and release along with NA
-adrenergic receptor (and Ach)
Purinergic receptors: - Many receptors: different actions
P1: adenosine receptor, GPCR - Excitatory in the bladder and the vas
P2X: ATP receptor, Ionotropic
P2Y: ATP receptors, GPCR deferens
- Inhibitory in the gut
 Parasympathetic nervous system
Acetylcholine: Synthesis, receptors and removal

Varicosity

Acetyl-CoA + Choline Post-ganglionic neuron

Ca2+ Acetate+ Choline

Post-junctional element
Acetylcholine
Muscarinic acetylcholine
Receptors
Voltage-gated Calcium channel

Acetylcholine esterase (AChE)

Choline transporter
 Parasympathetic nervous system
Acetylcholine: Synthesis, removal and receptors
Receptors Found in Effect of target tissue

MuscarinicAll parasympathetic targets Relaxation

Pre-junctional varicosity Inhibits ACh release

Eyes Miosis and near vision
Heart, kidney decrease contraction strength and rate
Airway smooth muscles Contraction
GI tract Increase secretion and motility

Overall, activation of the parasympathetic system

decreases the responsiveness of the body and
favors rest state
 Parasympathetic nervous system
Acetylcholine: Synthesis, removal and receptors:
the summary

Varicosity

Acetyl-CoA + Choline Post-ganglionic neuron

Ca2+ Acetate+ Choline

Post-junctional element

choline:
thetized in the cytoplasm of pre-junctional varicosities
nsported in vesicles
ny muscarinic receptors (mAChR) subtypes M1-M5 : different actions
CR, blocked by atropine
ChR could be found on the varicosities of the pre-junctional element (inhibits ACh release)
moved through degradation by the AChE
choline is recycled
 Parasympathetic nervous system
Non classical parasympathetic neurotransmitter:
nitric oxide (NO)

Varicosity

Acetyl-CoA + Choline Post-ganglionic neuron

Ca2+ Acetate+ Choline

Post-junctional element
 Parasympathetic nervous system
Non classical parasympathetic neurotransmitter:
nitric oxide (NO)

Varicosity
Calmoduline/Ca
2+
Post-ganglionic neuron
Calmoduli L-Arginine L-Citrulline +
ne NO

Ca2+ .
Post-junctional element
Voltage-gated Calcium channel
GC Ca2+
Nitric oxide synthase (NOS)
GTP cGMP
G PKG
C
Guanidylyl
cyclase Ca2+
PKG Proteine kinase cGMP
dependent ER
Relax Contractile apparatus
Plasma membrane calcium
transporter
Endoplasmic reticulum calcium
transporter
 Parasympathetic nervous system
Nitric oxide (NO) as a parasympathetic
neurotransmitter: the summary
Varicosity
Calmoduline/Ca
2+
Post-ganglionic neuron
Calmoduli L-Arginine L-Citrulline +
ne NO

Ca2+ .
Post-junctional element

GC Ca2+

GTP cGMP
tric oxide: PKG
Synthetized in pre-junctional varicosities cytoplasm Ca2+
Can be synthetized by the target cell
Synthesis calcium dependent ER
Relax Contractile apparatus
Very liposoluble (diffuses through the membranes)
Very short half-life
Activates cGMP pathways
Inactivation through PDE (degradation of cGMP)
 Autonomic nervous system
Examples of sympathetic / parasympathetic
crosstalk
 Autonomic nervous system
Example 1: the upper eyelid and the iris

Upper eyelid
The tarsal muscle, a small portion of the levator palpebrae superioris (skeletal
muscle), consists of smooth muscle fibers. It receive sympathetic innervation from
preganglionic neurons located in T1-T4 and contacting postganglionic neurons of the
superior cervical ganglion. Interruption of the sympathetic innervation to the tarsal
muscle results in pseudoptosis (partial drooping of the upper eyelid).
 Autonomic nervous system
Example 1: the upper eyelid and the iris

Iris
- Preganglionic neurons located in T1 - Preganglionic neurons in the Edinger-
- Synapse on neurons in the superior Westphal nucleus
cervical ganglia. - Axons leave the brain-stem through
- Postganglionic fibers innervate the the oculomotor nerve (CN III).
radial smooth muscle fibers of the iris. - Postganglionic neurons in the ciliary
- Activation results in contraction of the ganglion (in the orbit).
radial muscles of the iris, which causes - Innervate the circular smooth muscle
mydriasis (pupillary dilation) fibers of the iris.
- Activation leads to the contraction the
circular muscles of the pupil contract
which causes miosis (constriction of
 Autonomic nervous system
Example 1: the upper eyelid and the iris

Iris
- Preganglionic neurons located in T1 - Preganglionic neurons in the Edinger-
- Synapse on neurons in the superior Westphal nucleus
cervical ganglia. - Axons leave the brain-stem through
- Postganglionic fibers innervate the the oculomotor nerve (CN III).
radial smooth muscle fibers of the iris. - Postganglionic neurons in the ciliary
- Activation results in contraction of the ganglion (in the orbit).
radial muscles of the iris, which causes - Innervate the circular smooth muscle
mydriasis (pupillary dilation) fibers of the iris.
- Activation leads to the contraction the
circular muscles of the pupil contract
which causes miosis (constriction of
 Autonomic nervous system
Example 2: the baro-reflex

nAmb = nucleus ambiguus; Xn = vagus nerve; SG =

sympathetic ganglion; IML = intermedi-olateral cell
column of the spinal cord; CVLM = caudal ventrolateral
medullary depressor area; NTS = nucleus tractus
 Autonomic nervous system
Example 3: micturition
Bladder is under combined sympathetic, parasympathetic
and somatic control
During bladder filling, the
sympathetic tone (outflow from
T12-L2 through the lumbar
splanchnic nerve) activates 3
receptor of the detrusor muscle
(relaxation) and 1 of the
urethra and sphincter vesicae
(contraction) which avoid
When
releasemessage of full
of bladder bladder is
content.
sent to the brain: inhibition of
sympathetic system.

At the same time activation of

the parasympathetic projection
from the sacral region (S2-S4)
induces the contraction of
detrusor muscle and relax the
sphincter vesicae (AChM3R)
The somatic control maintains
the contraction of the external
urethral sphincter up to the
micturition.