Enrico Tiepolo
The autonomic nervous system (ANS)
The autonomic nervous system is a hierarchically
organized system under central control by the
hypothalamus. It displays several “stations” in
the brainstem (peri-aqueductal grey, parabrachial nucleus,
locus coeruleus, dorsal motor nucleus of the vagus, nucleus of
the solitary tract) each of which receives ascending
information and integrates it with
descending commands to send inputs to higher
structures and control the lower ones.
The ultimate purpose is the unconscious control of
body functions.
The effector side of the ANS originates from
preganglionic neurons located in the brainstem or
sacral spine (parasympathetic) or in the thoraco-
lumbar (T1-L2) spine (orthosympathetic), it can be
divided into a sympathetic, a parasympathetic and
an enteric nervous system.
Orthosympathetic preganglionic fibers (carrying information from the ventral horn of the spinal grey
matter) enter the spinal ventral root, leave it through the white ramus communicans to reach the
paravertebral ganglion; here they may:
• synapse on the sympathetic ganglion neuron
• proceed along the sympathetic (para-vertebral) chain to reach
sympathetic neurons at other levels
• bypass the ganglion and make synapses in ganglia removed from the
spine (celiac, superior mesenteric, aortic-renal, inferior mesenteric
ganglia and hypogastric plexus)
• reach the adrenal medulla, where they synapse on chromaffin
catecholaminergic cells
The postganglionic fibers originating from paravertebral ganglia either re-enter
the ventral root through the grey ramus to reach their target (in somatic
structures), or they proceed in sympathetic nerves to reach their target in the
viscera.
The sympathetic system, whose ganglia are mostly positioned in the paravertebral chain, is organized to
create a general response (generalized targets) and it makes sense because it innervates vessels, skin
etc. Thus, it makes sense that the information that comes out of a specific metamer may get into not only
the corresponding-level ganglia but also possibly goes up and down 2 or 3 ganglia in the paravertebral
chain in order to activate a more generalized response. The synapse between presynaptic and
postsynaptic neurons is far away from the target and therefore the activation is more diffuse.
Additionally, the sympathetic system has the possibility of being activated all together in a strong way –
activating all the nerves of the sympathetic system through activation of the adrenal medulla [where
we find chromaffin cells that are able to produce noradrenaline, and especially adrenaline, and
release it directly in the blood], which is able to release adrenaline, ergo will activate all the targets of
the SNS.
169 Body At Work II
, Enrico Tiepolo
Instead, the parasympathetic system is more directed for specific activities and so typically will
not be activated altogether.
Parasympathetic fibers exit through the III (oculomotor), VII (facial), IX (glossopharyngeal) and X
(vagus) cranial nerves, or through S2-S4 ventral roots, to reach the parasympathetic ganglia
located close (or in) the target organ.
In the head district sympathetic fibers may pass through parasympathetic ganglia.
Both systems reach the enteric nervous system, in which the myenteric and submucosal plexuses
play the role of (intramural) parasympathetic ganglia (as the sympathetic ganglia are located outside).
The afferent component of the ANS from the somatic structures is not easily isolated; visceral afferent
information is not so clearly split into ortho/para-sympathetic: it may travel in sympathetic nerves (the
dorsal root ganglion cell sends its centrifugal branch through the white ramus and the paravertebral
ganglion) or in cranial or sacral nerves.
Neurotransmitter and receptors
Descending and ascending connections in the CNS may use various neurotransmitters. The differences
in receptors and neurotransmitters are functional.
- All preganglionic neurons are cholinergic (they use acetylcholine).
They release ACh at ganglia onto neuronal nicotinic receptors (channels), so that ganglion
neurons do perform a significant information elaboration in real time; muscarinic receptors
are also present and interneurons using other transmitters and neuropeptides contribute to the
ganglionic circuits.
- All postganglionic neurons release their transmitters onto GPCRs on the effector cells. For the
sympathetic system, at the nerve terminal, NA and A will be released, while for the
parasympathetic ACh works here too.
Notice that effector cells can only be smooth muscle or secretory cells, so there never is the
need for a rapid (milliseconds), transient response.
o GPCRs coupled to Gq: =>, M3, M1 (are mostly in the cortex) and M5 (mostly in
the substantia nigra) produce secretion and smooth muscle contraction.
o GPCRs coupled to Gs mediate all the actions on the heart (F>) by enhancing the
pacemaker current and calcium fluxes and accumulation in the ER, and smooth
muscle relaxation (FG, F_).
o GPCRs coupled to Gi/0 counteract the actions of catecholamines in the heart – M2
(+ M4 are in the CNS) – or reduce the activity of the sympathetic system (α2) by
inhibiting the sympathetic outflow at the central level or by working as inhibitory
auto-receptors at sympathetic nerve terminals to reduce NA release. α2 receptors
are located on the pre-synaptic nerve terminal and when norepinephrine is released
some of it binds to α2 inhibiting further secretion of NA (negative feedback).
- In the parasympathetic division, post-ganglionic neurons are cholinergic (primary
neurotransmitter).
- In the sympathetic division, post-ganglionic neurons are mostly adrenergic (that is, epinephrine
and norepinephrine function as the primary neurotransmitters).
Notable exceptions to this rule include the sympathetic innervation of sweat glands and erector pilorum muscles
where the neurotransmitter at both pre and post ganglionic synapses is acetylcholine.
Another notable structure is the medulla of the adrenal gland, where chromaffin cells function as modified
post-ganglionic nerves. Instead of releasing epinephrine and norepinephrine into a synaptic cleft, these
cells of the adrenal medulla release the catecholamines into the blood stream as hormones.
170 Body At Work II
The autonomic nervous system (ANS)
The autonomic nervous system is a hierarchically
organized system under central control by the
hypothalamus. It displays several “stations” in
the brainstem (peri-aqueductal grey, parabrachial nucleus,
locus coeruleus, dorsal motor nucleus of the vagus, nucleus of
the solitary tract) each of which receives ascending
information and integrates it with
descending commands to send inputs to higher
structures and control the lower ones.
The ultimate purpose is the unconscious control of
body functions.
The effector side of the ANS originates from
preganglionic neurons located in the brainstem or
sacral spine (parasympathetic) or in the thoraco-
lumbar (T1-L2) spine (orthosympathetic), it can be
divided into a sympathetic, a parasympathetic and
an enteric nervous system.
Orthosympathetic preganglionic fibers (carrying information from the ventral horn of the spinal grey
matter) enter the spinal ventral root, leave it through the white ramus communicans to reach the
paravertebral ganglion; here they may:
• synapse on the sympathetic ganglion neuron
• proceed along the sympathetic (para-vertebral) chain to reach
sympathetic neurons at other levels
• bypass the ganglion and make synapses in ganglia removed from the
spine (celiac, superior mesenteric, aortic-renal, inferior mesenteric
ganglia and hypogastric plexus)
• reach the adrenal medulla, where they synapse on chromaffin
catecholaminergic cells
The postganglionic fibers originating from paravertebral ganglia either re-enter
the ventral root through the grey ramus to reach their target (in somatic
structures), or they proceed in sympathetic nerves to reach their target in the
viscera.
The sympathetic system, whose ganglia are mostly positioned in the paravertebral chain, is organized to
create a general response (generalized targets) and it makes sense because it innervates vessels, skin
etc. Thus, it makes sense that the information that comes out of a specific metamer may get into not only
the corresponding-level ganglia but also possibly goes up and down 2 or 3 ganglia in the paravertebral
chain in order to activate a more generalized response. The synapse between presynaptic and
postsynaptic neurons is far away from the target and therefore the activation is more diffuse.
Additionally, the sympathetic system has the possibility of being activated all together in a strong way –
activating all the nerves of the sympathetic system through activation of the adrenal medulla [where
we find chromaffin cells that are able to produce noradrenaline, and especially adrenaline, and
release it directly in the blood], which is able to release adrenaline, ergo will activate all the targets of
the SNS.
169 Body At Work II
, Enrico Tiepolo
Instead, the parasympathetic system is more directed for specific activities and so typically will
not be activated altogether.
Parasympathetic fibers exit through the III (oculomotor), VII (facial), IX (glossopharyngeal) and X
(vagus) cranial nerves, or through S2-S4 ventral roots, to reach the parasympathetic ganglia
located close (or in) the target organ.
In the head district sympathetic fibers may pass through parasympathetic ganglia.
Both systems reach the enteric nervous system, in which the myenteric and submucosal plexuses
play the role of (intramural) parasympathetic ganglia (as the sympathetic ganglia are located outside).
The afferent component of the ANS from the somatic structures is not easily isolated; visceral afferent
information is not so clearly split into ortho/para-sympathetic: it may travel in sympathetic nerves (the
dorsal root ganglion cell sends its centrifugal branch through the white ramus and the paravertebral
ganglion) or in cranial or sacral nerves.
Neurotransmitter and receptors
Descending and ascending connections in the CNS may use various neurotransmitters. The differences
in receptors and neurotransmitters are functional.
- All preganglionic neurons are cholinergic (they use acetylcholine).
They release ACh at ganglia onto neuronal nicotinic receptors (channels), so that ganglion
neurons do perform a significant information elaboration in real time; muscarinic receptors
are also present and interneurons using other transmitters and neuropeptides contribute to the
ganglionic circuits.
- All postganglionic neurons release their transmitters onto GPCRs on the effector cells. For the
sympathetic system, at the nerve terminal, NA and A will be released, while for the
parasympathetic ACh works here too.
Notice that effector cells can only be smooth muscle or secretory cells, so there never is the
need for a rapid (milliseconds), transient response.
o GPCRs coupled to Gq: =>, M3, M1 (are mostly in the cortex) and M5 (mostly in
the substantia nigra) produce secretion and smooth muscle contraction.
o GPCRs coupled to Gs mediate all the actions on the heart (F>) by enhancing the
pacemaker current and calcium fluxes and accumulation in the ER, and smooth
muscle relaxation (FG, F_).
o GPCRs coupled to Gi/0 counteract the actions of catecholamines in the heart – M2
(+ M4 are in the CNS) – or reduce the activity of the sympathetic system (α2) by
inhibiting the sympathetic outflow at the central level or by working as inhibitory
auto-receptors at sympathetic nerve terminals to reduce NA release. α2 receptors
are located on the pre-synaptic nerve terminal and when norepinephrine is released
some of it binds to α2 inhibiting further secretion of NA (negative feedback).
- In the parasympathetic division, post-ganglionic neurons are cholinergic (primary
neurotransmitter).
- In the sympathetic division, post-ganglionic neurons are mostly adrenergic (that is, epinephrine
and norepinephrine function as the primary neurotransmitters).
Notable exceptions to this rule include the sympathetic innervation of sweat glands and erector pilorum muscles
where the neurotransmitter at both pre and post ganglionic synapses is acetylcholine.
Another notable structure is the medulla of the adrenal gland, where chromaffin cells function as modified
post-ganglionic nerves. Instead of releasing epinephrine and norepinephrine into a synaptic cleft, these
cells of the adrenal medulla release the catecholamines into the blood stream as hormones.
170 Body At Work II
