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S1:Neuro: 1:00-2:00
Scribe: Sunita Jagani
Monday March 9, 2009
Proof: Sally Hamissou
Dr. Keyser
The Autonomic Nervous System: An Overview
Page 1 of 5
Abbreviations: NE= Neuroepinepherine NYP =Neuropeptide Y PNS-Parasympathetic Nervous System SNS=
Sympathetic Nervous System.
I. Introduction [S1]: Email him if you have any questions [email protected]
II. ANS [S2]
a. The autonomic nervous system comprises neural circuits that control many aspect of physiology. It works in
concert with the endocrine system and other organ systems to maintain homeostasis, which is the constancy of
the internal environment. The autonomic nervous system is distinct from the somatic system which controls
skeletal muscles.
b. One of the main roles of the ANS is to provide motor outflow to organ systems. The two divisions of the ANS:
i. The sympathetic division-SNS
ii. The parasympathetic division-PNS
iii. Each division has 2 levels of organization: the preganglionic and postganglionic neurons.
III. Figure 1.13 [S3]
a. The spinal cord extends from the base of the skull to the lumbar vertebrae. The neurons of the spinal cord
communicate with the periphery by axons that run in 31 pairs of spinal nerves.
IV. Figure [S4]
a. This is a cartoon overview of the autonomic system. We’ll consider the sympathetic and then the
parasympathetic divisions separately
b. They innervate the same organs. The sympathetic and parasympathetic tend to have opposite effects on organ
systems.
V. Figure [S5]
a. There is a major difference between the way the somatic and autonomic nervous systems innervate target
tissues.
b. For example, here is the motor neuron of the spinal cord, it sends its axons out through ventral root of the spinal
cord to innervate the skeletal muscles and makes the synapse at the motor end plate.
c. In contrast, the Autonomic nervous systems do it two ways.
i. There are cell bodies in the spinal cord and they project axons to autonomic ganglia, and these ganglia in
some cases project to the target tissue and innervate the target tissue. There is a synapse the
preganglionic cell and the ganglionic neuron that actually innervates the muscles.
ii. There is another type of organization in ANS. The cell body is in the CNS projects to the target tissue and
synapse onto neurons that are in ganglia close to the target tissue or they synapse on neurons that are
embedded in the tissue.
VI. Preganglionic neurons of the sympathetic system [S6]
a. The preganglionic neurons of the sympathetic system a.k.a. the thoracolumbar system called that because the
preganglionic neurons lie in the intermediolateral cell column in the spinal cord.
b. In humans, these are found between the 1st thoracic segment (T1) and the 3rd lumbar segment (L3), which is
why it’s called the thoracolumbar system.
c. The preganglionic cell bodies lie here and axons from preganglionic neurons exit the cord via the ventral spinal
nerve of that segment like other normal motor neuron. Here they synapse on the “ganglionic” neurons and the
neurons can be several different places.
i. These can be in sympathetic ganglia are interconnected and run up along side of the spinal cord that are
called “sympathetic chain”. These contain the cell bodies of the ganglionic neurons. So preganglionic send
an axons and enter the sympathetic ganglia in the chain and synapse with in it.
ii. The sympathetic ganglia that lie close to the spinal cord are the paravertebral ganglia. There are other
sympathetic ganglia that contain ganglionic neurons that are further from the spinal cord and are called
prevertebral ganglia.
iii. Summary: close to the spinal cord- paravertebral ganglia, and far from the spinal cord- prevertebral
ganglia.
d. These axons from the preganglionic neurons synapse on cells on the ganglionic neurons in the one of these
locations.
e. These are providing motor outflow to target tissues. They control smooth muscles, glands, and other tissues.
f. The sympathetic motor neurons receive sensory input from peripheral targets. The cell bodies lie in the dorsal
root ganglia of the spinal cord and they send processes bring in sensory information from the periphery and into
the spinal cord feeds back on to the preganglionic neurons.
g. So you have motor outflow and sensory inflow and you have a substrate for reflex actions.
VII. Figure 2 [S7]
a. This shows in a different way what the previous slide talked about.
S1:Neuro: 1:00-2:00
Scribe: Sunita Jagani
Monday March 9, 2009
Proof: Sally Hamissou
Dr. Keyser
The Autonomic Nervous System: An Overview
Page 2 of 5
b. Starts at the intermediolateral cell columns that contains the sympathetic preganglionic neurons go through the
ventral roots of the spinal cord to the paraverterbral or preverteberal ganglia, and there they synapse on the
ganglionic neurons and those cells send axons to the target tissue.
c. Here a gut related organs, we have sensory information that comes into the dorsal root ganglion (cell body is in
dorsal horn), enters the dorsal horn of the spinal cord, that synapse on the interneuron that conveys the
information into the preganglionic fibers.
d. These reflexes can occur at the level of the spinal cord without us being aware of it.
VIII. SNS is organized segmentally [S8]
a. The SNS is organized segmentally. This is an illustration for T3 and T4 of the thoracic spinal cord. The
interomediolateral spinal column projecting out through the ventral root of the spinal cord. These preganglionic
axons exit through the ventral root of the segment.
b. These axons can be myelinated or unmyelinated and can project to the paravertebral ganglion associated with
the same segment of the spinal cord, or it can be one more ganglion up or downstream of the that part of the
spinal cord. The actual roots of the neurons can be complicated. They can project to the postganglionic in the
paravertebral ganglia which is more distal.
IX. Sympathetic Nervous System Figure [S9]
a. The sympathetic preganglionic neurons provide output to the ganglion neurons which, in turn, provide input to
organ system.
b. If you look at the organization of the preganglionic of the length of the spinal cords, the rostral tissues are
innervated by the preganglionic cells that are more rostral partsof the throcolumbar spinal cord.
i. This organization is “viscerotopically” so that preganglionic innervation of structures in the head originate
rostrally, while output to the GI tract and other organs are most caudal (lumbar cord).
c. Important to remember is that these axons to the target take predicable courses through the body so during
surgery, major fiber bundles can be avoided so you don’t lose autonomic function.
d. Really important! An important specialization in the sympathetic system is the adrenal medulla, which by many
several criteria is a highly modified sympathetic ganglion.
i. It functions as an endocrine organ and releases epinephrine into the blood stream as well as other
molecules.
X. Parasympathetic Nervous System Figure [S10]
a. The preganglionic neurons of the parasympathetic system are found in nuclei in the brainstem, and in the sacral
spinal cord, so it is sometimes called the craniosacral division of the ANS because of the location.
i. Some of these preganglionic neurons send their axons out through the cranial nerves to targets in the head
such as the eye, salivary glands, etc.
ii. Others project into the thorax: bronchia, heart, pancreas lungs, intestine, stomach.
b. In this case, the organs themselves are innervated by the ganglionic fibers which are found in the ganglia that
are very close to the target tissues.
c. In some case, ganglionic fibers are impended into the tissue in loose assemblage of cells which is called
plexuses. They are less packed than a traditional ANS ganglia.
i. For example, the ciliary ganglion (behind the eye) is parasympathetic ganglia which projects to the iris and
the ciliary body.
ii. The cells also receive input from sensory neurons imbedded in the target tissue itself so it can go back to
CNS and control motor outflow.
XI. Brainstem Figure [S11]
a. This is the dorsal surface of the brainstem (at right) showing the location of the cranial nerve nuclei that are
either the source of the target of information that are leaving or entering the cranial nerves. The cranial nerve
nuclei are clusters of parasympathetic preganglionic neurons.
b. Some are purely visceral, some are somatic- the color key tells which is one is which.
c. I am not going to ask you remember all the CN.
d. Some of the CN nuclei generate motor commands out to target tissue, others receive sensory input and others
are mixed. For example, Edinger-Westphal nucleus, the inf. and sup. salivatory nulcei, and the dorsal motor
nucleus of the vagus are all visceral motor nuclei. So these are motor neurons that are sending motor
information out to the target tissue.
e. The axons of these cells travel in the cranial nerves.
f. Summary: some CN are visceral, sensory, or mixed.
XII. Figure 7 [S12]
a. Some of the ANS circuit can be fairly complex.
b. Input to the preganglionic neurons (sensory input ) and descending input from higher centers.
S1:Neuro: 1:00-2:00
Scribe: Sunita Jagani
Monday March 9, 2009
Proof: Sally Hamissou
Dr. Keyser
The Autonomic Nervous System: An Overview
Page 3 of 5
c. Output to the nucleus, the ganglionic neuron to one of the ganglia, the synapse can be extremely complicated.
Ganglionic neuron goes out to the target tissue.
d. The extensive CN that involves dorsal vagal nucleus.
e. Nucleus solitraus tract, receives sensory information from these structures.
f. Nucleus of ambiguous also provides output.
XIII. Visceral and Somatic Afferents [S13]
a. You have sensory information coming in from the somatic sensory neurons and visceral sensory neurons and
they are both are coming into the dorsal horn neurons. Early evidence that their projections to the relay neurons
overlapped. It wasn’t clear how somatic sensory was separating from visceral sensory.
i. Visceral sensation is like pressure, GI system is distended or when your bladder or stomach is really full.
There is a lot of feedback you are not aware of and aware of.
ii. Here is somatic and visceral afferents bringing back sensory feedback into the spinal cord or the brainstem.
iii. These cells terminate in the laminae I and V of dorsal horn of the spinal cord, and they terminate on relay
neurons which can either do local circuit or can send project to higher centers of the brain.
b. Less than 20 years ago it was found, although these visceral and somatic sensory input show similar trajectories
coming into the cord, they actually have distinct different distribution and densities.
c. Somatic terminates more superficially in dorsal horn, while visceral is different distribution is centered at the
intermediolateral column where the preganglionics are.
d. There are still things about the autonomic that are being investigated.
XIV.
Enteric Nervous System [S14]
a. In the walls of the intestine system, there is a whole other nervous system.
b. There are more neurons in the intestinal neurons than in the spinal cord. If you peel back the layers of intestine
wall, you can see the plexuses- loose networks of neurons that innervate the gut. Some neurons are sensory
that bring information into the CNS, some are motor controlling the secretions into the lumen of the gut.
c. Enteric neurons form two conspicuous and extensive networks (plexuses) of ganglia connective tissue.
i. One is located between the longitudinal and circular muscle layers of the wall that is called the myenteric
plexus and also referred to as the Auerbach’s plexus.
ii. The other plexuses is between the circular muscle layer and the inner mucosal layer called the
submucous(al) plexus and also called Meissner’s plexus.
iii. Know by both names because people refer to them differently.
d. There are more plexuses like pregrandular, deep plexus and villous plexus. There are probably 4 or 5 layers of
neural plexus within the gut. These control secretion into the gut, bring sensory information.
i. The most important thing that they do is to control motility (contraction of muscles to move through the
digestive system).
e. These cells do get input from the rest of the nervous system. If the incoming information from central structures
is eliminated, this part of the nervous system can act on its on mostly. It is modulated by the rest of the nervous
system, but it is not absolutely dependent on it.
f. The picture-vagal preganglionic projection into the gut, it ends to the embedded on the tissues so it’s
parasympathetic. Stained the plexus with Cuprolinic blue. These are the incoming axons from the ANS
preganglionics.
*******Slides 15-18 were tables that he just read off. If there was anything extra he added, I have included in the
descriptions under respective slides.
XV. Table 21.1 [S15]
a. Tried to summarize some of this information. Don’t ask you to memorize all of the table, but useful to show that
parasympathetic and sympathetic have opposite effects on many tissues. .
b. The columns show the target, location of preganglionic neurons, location and actions.
c. Some of these actions are used clinically to check ANS neural circuits.
d. He read off the table for the eye, lacrimal gland, salivary gland, heart, and lungs for all the columns.
e. The heart actions increases cardiac output
f. These actions on target tissue would be good pharmacology to target. There will be examples of it later.
XVI.
Table 21.1 Part 2 [S16]
a. He read off the table for stomach, small and large intestine, bladder, adrenal ganglionic.
b. The effect of the sympathetic system activation is shut things down to prepare for fight of flight. It’s preparing
you for the stressful situation, like taking OM part of neuro test again.
c. Sympathetic system is for stress
d. The adrenal ganglion is like a modified sympathetic ganglion, the cells in the ganglion act like modified neurons,
they dump catecholamine in blood stream.
S1:Neuro: 1:00-2:00
Scribe: Sunita Jagani
Monday March 9, 2009
Proof: Sally Hamissou
Dr. Keyser
The Autonomic Nervous System: An Overview
Page 4 of 5
XVII. Table 21.1 Part 3 [S17]
a. In many cases, the parasympathetic effect is opposite of sympathetic effect.
b. He read off the chart for the eye, submandibular, salivary, heart, and lungs.
c. Accommodation is changing the shape of the lens as things get closer or further.
d. While the sympathetic is ready for stressful things, the parasympathetic is rest and digest, reduces the heart
rate, calms everything down, and bring back down to homeostasis condition.
XVIII. Table 21.1 Part 4 [S18]
a. He read off the actions of the stomach , pancreas, ureter and bladder,
b. For the stomach, there is opposite actions then the sympathetic.
c. Because it causes the secretions, motility, of digestive organs, the PNS is called the rest and digest.
d. No effect on the adrenal gland.
XIX.
Table 20.2 [S19]
a. The pharmacology of SNS and PNS is amazing complex. This is just an intro.
b. The preganglionic neurons of both systems (PNS and SNS) utilize acetylcholine as the major neurotransmitter
at the synapse with the ganglionic neurons and the effects are mediated by nicotinic acetylcholine receptors.
c. Some preganglionic fibers also release neuropeptides and other neuroactive substances.
d. The postganglionic fibers of the parasympathetic system also release ACh and in this case the target tissue
muscarinic receptors mediate the response so it’s a G- protein- coupled receptor.
e. But the sympathetic postganglionic fibers primarily release norepinephrine, that affect several types of receptors
which are alpha1 and alpha 2, beta 1, and beta 2
f. For cholergenic subtypes in target tissues include M1 , M2, M3, M4, M5. Some tissues of have more than one.
*******He read off these charts, which is easier to look at in the power points.
He went through the receptors and what tissues express them and responses for the tissues which he read of the
chart for alpha 1 and 2.
For beta 1 and 2, he just mentioned which tissues have them, nothing about functions.
For cholergnic subtypes in target tissues include M1 , M2, M3, he talked about where they are, and just said “these
are the effects.”
XX. Table 48.1 [S20]
a. The pharmaceutical industry has spent a lot of money on this area, that targets autonomic synapses. Some of
these drugs are not used anymore.
b. The column includes the receptor, what drug does, and the drug that targets that, and the medical use.
c. For example, cholerginic M-3 Ach induced secretion like salivary glands. Atropine non-selective antagonist
blocks it, and it has been used for drooling in Parkinson’s patients.
d. Muscarin M1 inhibits the release of Ach from the NE from ANS nerve terminals.
e. Tranzapine prevents ulcers.
d. Lots of drugs used to treat hypertension by targeting the ANS including prazosin. yohimbine has an interesting
application.
f. These are few of many drugs that have been developed to target the ANS.
XXI.
Figure Visceral Afferents [S21]
a. The visceral sensory afferents that produce axon reflexes. Visceral and cutaneous afferents release transmitters
from the tachykinin family. Don’t worry about this family too much.
b. When action potentials are generated peripherally, they are propagated centrally. They can also propagated
other branches of the same sensory neuron causing localized release of tachykinins in the affected terminals
and causes responses in the target tissues reflexly just by this part of the cell here.
XXII. Neurotransmission Figure [S22]
a. Two unique NT were identified.
b. ATP can be released at synapse and has its own receptors (purigenic receptors) and are ligand gated ion
channles, it’s a cationic channel - so when it’s open the sodium flows and causes depolarization.
c. Another discovered in the ANS was nitric oxide. It’s a gas that’s produced by enzyme nitric oxide synthase on a
substrate and cofactor. As a gas instead vesicular release, it can diffuse at long distances so can affect other
cells..It affects vasculature, so figure out if vasculature to see if its dilated and constricted. This system is
targeted by pharmaceutical like vigra by targeting the nitric oxide pathway.
d. Here is a sympathetic terminal onto smooth muscles cell in some target tissue.
i. Here is there is co-transmission of NE, NPY, and ATP. Three NT being released so, there are there
different ways to activate target tissues. They do things at different time courses.
1. In phase 1, rapid depolarization, ATP binds to pureginic receptor (P2X) and it is ligand gated ion
channel, which causes depolarization which activates voltaged gated Ca channels which causes an
increase intracellular Ca. That’s responsible for the first peak.
S1:Neuro: 1:00-2:00
Scribe: Sunita Jagani
Monday March 9, 2009
Proof: Sally Hamissou
Dr. Keyser
The Autonomic Nervous System: An Overview
Page 5 of 5
2. In phase 2, NE binds to alpha 1 adergenic, which via G-coupled activating signal cascade involves
with phospholipase C and IP3, causing release of calcium intracellular stores and the second
depolarization causing contraction.
3. In phase 3, when present, NPY binds to a NTP receptor: Y1 receptor which is another G-coupled
mechanism, with a mechanism not understood somehow causes an increase in intracellular [Ca2+]
and thus produces the slow phase of contraction.
e. If you look at muscle contraction, it is brought by three separate phases.
XXIII. Figure Central Autonomic Nervous System [S23]
a. There is a central autonomic network that coordinates autonomic function, and this system involves structures in
the brain stem and forebrain. Among the key structures are the nucleus of the solitary tract, which receives
sensory input from organs such as the heart and then projects to other structures in the spinal cord and
brainstem. This is the basis of reflex actions.
XXIV. Input figure [S24]
a. This cartoon illustrates an example.
b. Here is the heart, chain ganglia, brainstem, spinal cord.
c. Sensory input from either the chemoreceptor or baroreceptors in the heart that tell something about cardiac
output is sent to the brain stem, and through 1 or 2 synapses ends up activating preganglionic neurons in the
intermediolateral column in thoracic spinal cord. These cells send axons to ventral root, and they synapse on
the ganglionic neuron in the sympathetic chain ganglia, and that sends axon to heat muscles and provides input
to the heart, which tries to bring things back to whatever condition that was signaled by the sensory receptors.
d. Reflex action that can change cardiac output without use knowing about it.
XXV. Diseases Associated with ANS [S25-S26]
a. Lots of diseases that are related to ANS.
b. Catch all- Dysautonomia literally means dysregulation of the autonomic nervous system. The autonomic
nervous system is the master regulator of organ function throughout the body. It is involved in the control of
heart rate, blood pressure, temperature, respiration, digestion and other vital functions.
i. Dysregulation of the autonomic nervous system can produce the apparent malfunction of the organs it
regulates. For this reason, dysautonomia patients often present with numerous, seemingly unrelated
maladies different organ systems can be because of generalized dysautonomia.
c. Postural Orthostatic Tachycardia Syndrome
i. Often more simply referred to as postural tachycardia syndrome, or POTS, this disorder is characterized by
the body's inability to make the necessary adjustments to counteract gravity when standing up. The
defining symptom of POTS is an excessive heart rate increment upon standing. However, there are a
multitude of other symptoms that often accompany this syndrome. As such, POTS can be a difficult
disorder to detect and understand.
d. Neurocardiogenic Syncope (NCS)
i. Sometimes referred to as neurally mediated syncope or vasovagal syncope, this disorder is characterized
by an episodic fall in blood pressure and/or heart rate that results in fainting .
e. Pure Autonomic Failure (PAF)
i. A degenerative disease of the peripheral nervous system characterized by a marked fall in blood pressure
upon standing (orthostatic hypotension). The orthostatic hypotension leads to symptoms associated with
cerebral hypoperfusion, such as dizziness, fainting, visual disturbances and neck pain. Other symptoms
such as chest pain, fatigue and sexual dysfunction may also occur. Symptoms are worse when standing
and are sometimes relieved by sitting or lying flat
f. Multiple System Atrophy/Shy-Drager Syndrome (MSA)
i. A degenerative disease of the nervous system, MSA usually becomes apparent when one is in their fifties
or sixties. Variety of symptoms including: genitourinary dysfunction, impotence, headache, neck pain,
dimming of vision, frequent yawning, orthostatic hypotension, gait disorder, sleep disorders and
hoarseness may occur with multiple system atrophy, Loss of sweating, rectal incontinence, iris atrophy,
external ocular palsies (paralysis of eye muscles), rigidity, tremor, and wasting of distal muscles may also
occur.
ii. MSA is a fatal illness, and patients usually die within ten years of onset. There are no treatments that are
useful of for this disease.
g. End {45:26}