The Autonomic Nervous System Joseph De Soto MD, PhD, FAIC

overview The autonomic nervous system regulates and integrates the moment by moment activities of the body. Many medications act by modulating the function of the autonomic nervous system. The autonomic nervous system and the somatic nervous system are parts of the efferent nervous system.

Nervous system The nervous system can be divided into the central nervous system of the brain/spinal cord (nuclei and tracts) and the peripheral nervous system (ganglia and nerves). The peripheral nervous system has an afferent component of the sensory nerves and the previously described efferent somatic (voluntary) and autonomic (involuntary) nervous system The autonomic nervous system is composed of the 1. Parasympathetic 2. Sympathetic and, 3. Enteric nervous systems

Central Autonomic system The central autonomic network is composed of both hypothalamic and extra-hypothalamic nuclei. Some of these sites regulate sympathetic outflow whereas others regulate parasympathetic outflow. The single most important hypothalamic nucleus of the central autonomic network is the paraventricular nucleus. The locus ceruleus and the rostral and caudal ventrolateral medulla and the serotonin-containing neurons of the pontine and medullary raphe nuclei are associated with control of the sympathetic nervous system. The extra-hypothalamic sites associated with control of parasympathetic outflow include the central nucleus of the amygdala, the dorsal motor nucleus of the vagus, the nucleus ambiguus, the periaqueductal gray, and the parabrachial nucleus.

Anatomy of parasympathetic The parasympathetic nervous system arises from cranial nerves III (oculomotor), VII (facial) , IX (glossopharyngeal) , X (vagus) and sacral nerves arising from S2, S3 and S4. About 90% of the parasympathetic nervous system is from cranial nerve X. Preganglionic fibers are long while post ganglionic fibers are short in the parasympathetic nervous system. The organs of the thoracic and abdominal cavity are innervated by the parasympathetic nervous system.

Anatomy of Sympathetic The sympathetic nervous system emergence from the spinal cord from T1 and L2 and synapse with the paravertebral ganglia. From the paravertebral ganglia nerves synapse at ganglia near the organ innervated. Hence, unlike the parasympathetic nervous system the parasympathetic nervous system is composed of short preganglionic fibers and long post ganglionic fibers.

Anatomy of the enteric The enteric nervous system is the third portion of the autonomic nervous system and is composed of nerves that innervate the gastrointestinal tract, the pancreas and gallbladder. This system is relatively independent of the CNS though it can be modulated by the parasympathetic and sympathetic nervous system. The enteric nervous system controls the motility, exocrine, endocrine and the microcirculation of the GI tract. The neurons of the ENS are collected into two types of ganglia: myenteric (Auerbach's) and submucosal (Meissner's) plexuses which control motility and glandular excretion respectively.

Function of the parasympathetic nervous system The parasympathetic nervous system is required for life and helps maintain bodily functions such as digestion and protein production by the liver. It is very important for maintaining homeostasis. The parasympathetic system does not fire it neurons in unison but more discretely usually organ by organ not all at once. A preganglionic parasympathetic fiber will synapse on only one post parasympathetic ganglion. The parasympathetic system predominates during time of “rest and digest”.

Function of the sympathetic nervous system The sympathetic nervous system often functions together as a unit especially in the presence of fear and intense exercise. The reactions of the sympathetic nervous system may occur via the direct stimulation of the effector organs by the sympathetic innervation or hormonal release by the adrenal medulla. A preganglionic sympathetic fiber will synapse on more than one postsynaptic ganglion. The sympathetic nervous system will mobilize energy stores , and divert blood flow from the internal organs and skin to the muscles. The flight of fight response.

Somatic nervous system Whereas the autonomic nervous system under involuntary control the somatic nervous system. This is an efferent system that puts muscles un voluntary control The somatic nervous system controls the conscious movement of skeletal muscle. The one fiber of the somatic nervous system will innervate 1 to 100 or more muscle fibers. The finer the movement of the muscles the smaller amount of muscle fibers are innervated by a single nervous system fiber.

Innervation Most organs receive dual innervation by the parasympathetic and sympathetic nervous system. When this occurs the influence of each system is opposed to one another. For instance the parasympathetic nervous system slow down respiration while the sympathetic nervous system will increase respiration. Some organs are only innervated by the sympathetic nervous systems, such as adrenal medulla, kidney, sweat glands and pilomotor muscles.

Contrasting the sympathetic and parasympathetic nervous system

neurotransmitters The neurotransmitters used by the autonomic nervous system are acetylcholine and norepinephrine/epinephrine. The parasympathetic nervous system releases of acetylcholine from the preganglionic fiber and from the post ganglionic fiber. The sympathetic nervous system stimulates release of acetylcholine from the preganglionic fiber and norepinephrine from the post ganglionic fiber. The Adrenal medulla medullar secretes epinephrine. The somatic nervous system releases acetylcholine at the skeletal muscle motor end plate.

Nicotinic receptors Nicotinic acetylcholine receptors, or nAChRs, are neuron receptors. They are subtype of cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the presynaptic and postsynaptic sides of the neuromuscular junction. As ionotropic receptors, nAChRs are directly linked to ion channels and do not use second messengers as metabotropic receptors do. Nicotinic acetylcholine receptors are the best-studied of the ionotropic receptors There are two major types Nm and NN which are at the neuromuscular end plate and neuron respectively. The NN is found and at the initial ganglion of both the parasympathetic and the sympathetic nervous system

Muscarinic receptors There are four receptors that acetylcholine will bind to the 1) Nicotinic receptors, and the Muscarinic receptors: M1, M2 and M3, M4 and M5 receptors. The M1 receptor is found in the CNS, salivary glands, and stomach. The M1 receptor is important for memory. Gq protein utilized The M2 receptor is found in the heart. Gi protein used. The M3 receptor is found in the gut, bronchioles, and sphincters. They contract the muscles of gut and airways and relax sphincters. Gq protein used. M4 (Gi protein used ) and M5 (Gq protein used)are receptors found in the brain.

Cholinergic receptors

Adrenergic receptors Norepinephrine and epinephrine can bind to 5 receptor subtypes: α1,α2, β1, β2, and β3. α1 receptors are found on vascular smooth muscle and sphincters and cause contraction. Gq protein utilized. α2 receptors are found on the presynapric cleft of neurons and inhibit release of neurotransmitter. Gi protein utilized.

Adrenergic receptors β1 receptor is found on cardiac muscle and the kidney. It speeds up heart rate and increases renin secretion. Gs protein utilized. β2 receptors relax the bronchi smooth muscle, increase glycogenolysis in the liver and skeletal muscle and increase gluconeogenesis in the liver. Gs protein utilized. β3 receptors are found in the fat and increase lipolysis. Gs protein utilized.

IP3, DAG increased CAMP decreased cAMP increased cAMP increased cAMP increased

Cyclic AMP The second messenger cAMP is activated as follows. An agonist binds the G-Protein receptor. A GS subunit bind adenylate cyclase. (A Gi subunit will inhibit adenylate cyclase) Adenylate cyclase then produces cAMP (cyclic adenosine monophosphate) for ATP. 4 cAMP molecules will bind to the regulatory subunit of protein kinase A activating it. Protein kinase A will then activate and deactivate other enzymes by phosphorylating them. The reaction continues until cAMP decomposition into AMP is catalyzed by the enzyme phosphodiesterase.

cAMP is degraded to AMP by phosphodiesterase

IP3 & DAG Once a G-coupled receptor is bound by an agonist it will allow the Gprotein to dissociate into the Gα and Gβγ subunits. The subtype used of the Gα will be Gq. The Gq-ATP subunit will activate phospholipase C. Phospholipase C will convert phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). The IP3 will travel to the endoplasmic reticulum (ER) and bind the ligand-gated Ca2+ channel that is found on the surface of the ER. Allow intracellular Ca2+ to increase. DAG remains on the cell membrane and activates the signal cascade by activating protein kinase C (PKC).