BIOL 2480 - Autonomic

"stress", Defined as "the nonspecific response of the body to any

demand made upon it."

Body responds through

neural and hormonal mediators

Stress has

•Multiple targets

So stress isn't good or bad, it is just how the body responds overall to external demands, just anything that

forces your bodies homeostatic control to shift

Neural mediators and sympathetic and

parasympathetic systems.

Hormonal are driven by

Hypothalamic pituitary adrenal (HPA) axis

Driven by the "

autonomic" nervous system

Sympathetic ("flight or fight") and

parasympathetic ("rest and digest") systems constantly trade off

An essential difference between somatic and autonomic systems is the

autonomic ganglia.

The lower motor neurons, the ones that actually cause the muscle or gland to have an effect, start outside the

CNS with the cell bodies clustered into autonomic ganglia (make them say what a ganglion is).

These are the

postsynaptic neurons

These are the postsynaptic neurons. They receive input from neurons that start inside the CNS, the

presynaptic neurons, that have cell bodies in the spinal cord or brainstem.

As we will get to, the location of the ganglia will differ between

symp and parasymp, with symp tending to be closer to the spinal cord.

•Fight or flight,

-Dilate pupil, Open airways, Inhibit digestion, Glucose production

Chain ganglia are close to

•spinal cord.

Visceral ganglia are

•further away

-Celiac ganglia

-Mesenteric ganglia

There are two sets of sympathetic ganglia. The chain ganglia run along the length of the spinal cord, getting

presynaptic neurons from the thoracic and lumbar area.

These are close to the spinal cord with long postsynaptic neurons going to the target organ. Many ganglia go to the heart to help control heart rate. There are 3 ganglia that are further from the spinal cord: the

celiac ganglia branch out to control the stomach, gall bladder, pancreas and liver (in conjunction with the enteric); the superior mesenteric ganglion controls the intestines; and the inferior controls the rectum, bladder and penis.

Ganglia much closer to

target organs

Brainstem origin for many

preganglionic neurons

-Edinger-Westfall nucleus

•Pupil reflex

-Pons & medulla

•Spit & tears

-Dorsal motor nucleus of vagus

•Stomach, pancreas, upper intestine

Note here at parasymp preganglionics are longer and

more branched than symp.

Postganglionics are the opposite. Preganglionics only originate from

brainstem and sacral spinal cord.

Edinger-Westfall- group of preganglionic neurons located at top of brainstem. Axons leave via

oculomotor nerve (III). Controls pupil dilation and lens accomodation (stretch). Form synapses at ciliary ganglion

Pons & Medulla send out numerous axons that synapse in salivary ganglia and modulate

saliva and tear production. You have many different salivary glands so you need fine scale control.

Dorsal motor nucleus - stimulates digestion, pancreatic enzymes (insulin & glucagon). Stimulates

gall bladder, dilates blood vessels in small intestine.

Neurons in the gut can operate

•independently, although they are modified by sympathetic and parasympathetic innervation.

Consists of two major nerve

•plexuses

-Myenteric

Submucous

Controls function of GI tract, pancreas and gallbladder

Has local

sensory neurons, interneurons and motor neurons

Responds to changes in tension of walls and

changes in chemical environment

Motor neurons control gut smooth muscle, local blood vessels, secretion.

Plexuses are another name for neural network. Both extend along entire length of gut.

Myenteric and submucous

Myenteric - between 2 muscle layers (longitudinal and circular). Controls

motility

submucous - between circular muscle and mucosa. Controls

secretion

Both plexuses are connected to each other and both contain motor neurons for

secretion and motility, just that myenteric has more for motility and submucous has more for secretion.

Synaptic contacts much less specialized in

autonomic.

Instead of defined terminal you see autonomic

varicosities (swellings).

Varicosities are

transient - they are constantly changing.

Main point here is that axon does not end at a terminal like we covered previously. Instead the neurotransmitter vesicles are all clumped together into

localized swellings called varicosities

There is no defined active zone in these varicosities and it is not entirely clear (at least to me) the steps involved

in vesicle fusion.

Note: because of these differences, it is not strictly appropriate to call this a synapse. Rather we will talk about

prejunctional and postjunctional processes.

The varicosities can change location along the axon fairly easily. Around effector tissue, axons become

varicose, with the varicosities occuring at 2-10 micron intervals. Axons are myelinated but lose their coating in the varicosities.

2. Neurotransmitters more varied, therefore effects

more varied

Old view: sympathetics are

adrenergic,

parasympathetic are

cholinergic

This is still partially correct. In general, both sympathetic and parasympathetic presynaptic fibers release ACh at the

ganglionic synapse

For both this acts on nicotinic receptors at the

postsynaptic dendrite.

Between postsynaptic cell and target tissue the sympathetics tend to release

NE onto adrenergic receptors and parasymps release ACh onto muscarinic receptors.

Norepinephrine

(sympathetic)

acetylcholine

(parasympathetic)

•Norepinephrine (sympathetic) and acetylcholine (parasympathetic) still major players.

Sympathetic also commonly uses _________________________ as cotransmitter

ATP and neuropeptide Y

parasympathetic may use

ATP & vasoactive intestinal polypeptide (VIP).

___________ are also common.

Neuromodulators

For something to be considered a cotransmitter it must have a

specific action on the effector organ itself

Neuromodulators do not have direct actions on effectors but instead

change the activity of the neurotransmitter somehow.

The same substance can also play both roles. Neuromodulators can be directly released from

varicosities or can come from other sources (cytokines, hormones, etc)

The majority of autonomic nerve fibers contain a mix of many different neurotransmitters that

vary in proportion in different tissues and species during development and disease."

Junctional cleft is the space between the

varicosity and the effector muscle.

Spacing can modulate effects of

co-transmitters.

I autoinhibition: example is of vas deferens. Only about 20 nm separates vas deferens from varicosities. Norepi and ATP get

cotransmitted.

I autoinhibition: example is of vas deferens. Only about 20 nm separates vas deferens from varicosities. Norepi and ATP get cotransmitted. If stimulation keeps coming then

then neuropeptide Y is released, inhibiting release of norepi or ATP. (neuromodulation)

II autoinhibition & potentiation: a cleft of 100-500 nm as in many blood vessels. First get release of

norepi/ATP

II autoinhibition & potentiation: a cleft of 100-500 nm as in many blood vessels. First get release of norepi/ATP. As stimulation continues NPY aslo gets released which enhances effects of

NA/ATP.

If stimulation keeps going, NPY builds up in

cleft and eventually inhibits norepi/ATP release

III Potentiation: With large cleft spacing (1000-2000 nm) as is typical of large arteries, NPY only serves a

neuromodulatory role. Essentially concentrations don't build up enough to inhibit release prejunctionally.

Different varicosites can influence each other and their

•effect can vary dependent upon location.

autoinhibition: transmitter X gets released and has some direct effect on

effector muscle/gland.

autoinhibition: transmitter X gets released and has some direct effect on effector muscle/gland. The same substance can also shut down release by binding to a

receptor on the varicosity. Feedback control

Cross-talk: X & Y in separate varicosities can both affect the

muscle (in this case antagonistically) but can also have neuromodulatory role on each other.

Synergism: Both X & Y,whether in the same varicosity or in different ones, can act directly on the muscle but also can have

i.neuromodulatory role on each other postjunctionally to enhance action

Opposite actions: X & Y can have opposite actions on different effector sites or can have a different effect depending on status of

effector organ

Ex of latter: if Uterine artery is "high tone" (stretched), X will make it

relax (inhibit)

If artery is "low tone" (relaxed) Y will make it

tense. Two balance each other to modulate tone.

Effect can also depend on what

co-transmittors are released.

Example: Norepinephrine binds to

α1 receptor for slow contraction,

ATP binds to

P2x receptor for fast contraction.

ATP and norepi are stored in small granular vesicle (SGV), neuropeptide Y is stored in

large granular vesicles (LGV).

ATP binds to P2x receptors (ionotropic) and results in

rapid excitatory junctional potential (EJP).

ATP binds to P2x receptors (ionotropic) and results in rapid excitatory junctional potential (EJP). Causes calcium

releases and a quick contraction.

Norepi (NA) binds to alpha 1 receptor (metabotropic) causing formation of

IP3 which then releases intracellular calcium and a slow contraction

NPY released from LGV can act directly synergistically on both P2x and

alpha 1 to enhance their effects but can also work prejunctionally to inhibit release of ATP and NA.

Effect at the organ depends on how many

muscle bundles get stimulated, directly or indirectly.

The cross-hatched muscle cells get directly stimulated by release of neurotransmitter at the varicosity. The junction potentials will spread quickly from the directly innervated cells to

nearby coupled cells (hatched).

If a large enough area of effector muscle is depolarized, a propagated action potential will spread to the

indirectly coupled cells (Remind them that most smooth muscle consists of cells electrically coupled together)

Notice the difference in pattern. Visceral will have fastest activation in narrow band so can get local

effect. Vascular has it more spread on one surface and then goes deeper with time.

•Ganglionic transmission can be:

Fast EPSP -

-Slow EPSP

-IPSP

Fast EPSP -

-instantaneous

Slow EPSP -

-longer lasting

ACh released from preganglionic binds to nicotinic receptors and causes

large, fast EPSP. Primary synaptic pathway for both symp and parasymp.

Slow EPSP happen when postsynaptic has muscarinic receptors. Smaller than

fast (note scale) but longer lasting. Result from opening of Na+ and Ca2+ channels and closing of K+.

Peptadergic EPSP can last up to a minute or more and works via same mechanism as slow

EPSP. Substance P is a common ligand for peptadergics

IPSP - mediated by muscarinic receptors that cause K+ channels to

open, causing K+ to leave and Em to hyperpolarize.

Visceral sensory inputs travel to nucleus of the

solitary tract (medulla) topographically.

•From there it goes to 3 locations.,

1. Preganglionic neurons

2. integrative areas such as reticular formation and forebrain

3. Various spots in the brain

3. Various spots in the brain

lateral reticular formation

- periaqueductal gray matter

- amygdaloid complex

How does brain regulate autonomic outputs? Direct outputs are found in

hypothalamus, parabrachial nucleus, solitary tract and other brainstem centers

There are also lots of other side connections between these and

autonomic preganglionic fibers.

Hypothalamus is

autonomic integrating center

Hypothalamus, Takes in sensory info, compares it to

set points