SDJONIH

NEUROPHYSIOLOGYAutonomic Nervous System

S DJONI HUSODO

I. Divisions A. Sympathetic

• fight or flight response

B. Parasympathetic

• rest and digestionII. Involuntary Motor System

A. Autonomic vs. Somatic motor systems

1. Somatic• voluntary• direct synapse

• excitatory

2. Autonomic• involuntary

• disynaptic (preganglion, postganglion)

• Excitatory and inhibitory

III General nerve pathways

A. Sympathetic

• Preganglion cell body – gray matter

• axons move through ventral root of spinal nerve

• synapse w/ postganglion at sympathetic chain ganglion

• axons of postganglions exit via

Spinal nerve

Sympathetic nerve

Exceptions: some pre do not synapse at symp chain

Splanchnic nerve

axons of preganglion exit Splanchnic nerve and

synapse at collateral ganglion

Adrenal gland preganglion synapses directly w/adrenal

B. Parasympathetic

• cell bodies of preganglion – brainstem (nuclei)

and sacral region of spinal cord• axons move through cranial nerves

and through spinal nerves

• synapse w/ postganglion at ganglia near or in the target

IV. Signal transmission

A. Sympathetic

• Preganglion secretes Acetylcholine (Cholinergic)

• Postganglion – receptor = Nicotinic

• Postganglion secretes Norepinephrine (Adrenergic)

B. Parasympathetic

• Preganglion secretes Acetylcholine (Cholinergic)

• Postganglion – receptor = nicotinic

• Postganglion secretes Acetylcholine

• Target (Smooth muscle, heart, glands)

receptor = muscarinic

V. ANS generalized

A. Regulated

B. Excitatory and inhibitory

• depends on the target organ

C. Opposite effects

VI. Autonomic control

A. Cardiovascular function

• Sympathetic: Norepinephrine -

Increases cardiac muscle contractions

Increases blood pressure

• Parasympathetic: Acetylcholine

Decrease in cardiac output due to decrease in

calcium influx

B. Pupillary light reflex

1. Parasympathetic

• constricts pupil

2. Sympathetic

• Dilates pupil

C. Salivary glands

1. Sympathetic

• viscous secretion/ vasoconstriction of blood vessels

2. Parasympathetic

• watery secretion/ vasodilation of blood vessels

• Target (smooth muscle, cardiac, glands)

Receptor = Adrenergic (α,β)

Sweat Glands

• Preganglion secretes Acetylcholine

• Postganglion – nicotinic receptor

• Postganglion secretes Acetylcholine

• Sweat gland – muscarinic receptor

The parasympathetic division consists of a sacral and cranial part.

In the cranium the PSN originate from cranial nerves •CN III (oculomotor nerve)•CN VII (facial nerve)•CN IX (glossopharyngeal nerve) •CN X (vagus nerve).

In the sacral region of the body the PSN is derived from spinal nerves S2, S3 and S4, commonly referred to as the pelvic splanchnics.

Figure 11-11: Summary of efferent pathways

Principles of Neural Science, 3rd Ed. Kandel et al., p. 763

Sympathetic Parasympathetic

thoracic

lumbar

sacral

brainstemcranial nerves

Rockman et al., (2002) Nature 415:206-212

G-Protein Coupled Receptors

R

Ca++

PKC

Ca++Endoplasmic Reticulum

Gq

PLC

ProteinProtein-P

A

DAG

IP3

PIP2

Phospholipase C, Inositol Trisphosphate (IP3), Ca2+ and Diacylglycerol, Protein Kinase C (PKC)

PLC – phospholipase CPIP2 – phosphatidylinositol bisphosphateIP3 – inositol trisphosphate

DAG – diacylglycerolPKC – protein kinase C

Two or “Three” Subdivisions of the Nervous System

Voluntary Autonomic Enteric

Innervates skeletal muscle smooth musclecardiac musclesecretory glands

intestinecontrols intestinal motility secretion absorption

Neurotransmitter ACh norepinephrineAChneuropeptides

norepinephrineAChserotoninneuropeptides

Receptors nicotinic muscle AChR

adrenergic GPCRsmuscarinic ACh GPCRsnicotinic neuronal AChR

GPCRs

?

Subdivisions of the Autonomic Nervous System

Sympathetic Parasympathetic

PrimaryNeurotransmitter

norepinephrineepinephrine (~20%) acetylcholine

Receptors&

SecondMessenger

Systems

Adrenergic GPCRs1 – IP3/DAG, [Ca2+]i PKC2 - cAMP/PKA

1 - cAMP/PKA2 - cAMP/PKA3 - cAMP/PKA

Muscarinic GPCRsM1 – IP3/DAG, [Ca2+]i PKCM2 – cAMP/PKA, PI(3)KM3 – cAMP/PKA, IP3/DAG, [Ca2+]i PKCM4 – M5 – IP3/DAG, [Ca2+]i PKC

Adrenal Medulla(epi:norepi::80:20)

Agonist potency order

Selected actionof agonist

Mechanism

α1:Norepinephrine > epinephrine >> isoprenaline

Smooth muscle contractionglycogenolysis gluconeogenesis,

Gq: phospholipase C (PLC) activated, IP3 and calcium up

α2:Epinephrine ≥ norepinephrine >> isoprenaline

Smooth muscle constriction and neurotransmitter inhibitioninhibition of insulin. induction of glucagon

Gi: adenylate cyclase inactivated, cAMP down

β1

Isoprenaline > epinephrine = norepinephrine

Heart muscle contractionRenin releaseLipolysis

Gs: adenylate cyclase activated, cAMP up

β2

Isoprenaline > epinephrine >> norepinephrine

Smooth muscle relaxationLipolysis Anabolism in skeletal muscle

Gs: adenylate cyclase activated, cAMP up (also Gi, see β2)

β3

Isoprenaline = norepinephrine > epinephrine

Enhance lipolysis

Gs: adenylate cyclase activated, cAMP up

1. The M1 muscarinic receptors (CHRM1) are located in the neural system.

2. The M2 muscarinic receptors (CHRM2) are located in the heart

3. The M3 muscarinic receptors (CHRM3) , the smooth muscles of the blood, lungs causing bronchoconstriction, smooth muscles of the gastrointestinal tract (GIT), which help in increasing intestinal motility and dilating sphincters. The M3 receptors are also located in many glands that help to stimulate secretion in salivary glands

4. The M4 muscarinic receptors: Postganglionic cholinergic nerves, possible CNS effects

5. The M5 muscarinic receptors: Possible effects on the CNS

1. D1-like family receptors is coupled to the G protein Gαs

activates adenylyl cyclase,increasing cAMP.The D1 and D5 receptors are members of the D1-like family

2. D2-like family receptors is coupled to the G protein Gαi, inhibiting adenylate cyclase inhibits the formation of CampD2, D3 and D4 receptors are members of the D2-like family

Dopamine receptor

Family Type Mechanism Potential

5-HT1Gi/Go-protein coupled.

Decreasing cellular levels of cAMP.

Inhibitory

5-HT2Gq/G11-protein coupled.

Increasing cellular levels of IP3 and DAG.

Excitatory

5-HT3

Ligand-gated Na+ and K+ cation channel.

Depolarizing plasma membrane.

Excitatory

5-HT receptor

5-HT4Gs-protein coupled.

Increasing cellular levels of cAMP. Excitatory

5-HT5Gi/Go-protein coupled.[4]

Decreasing cellular levels of cAMP. Inhibitory

5-HT6Gs-protein coupled.

Increasing cellular levels of cAMP. Excitatory

5-HT7Gs-protein coupled.

Increasing cellular levels of cAMP. Excitatory

GABA receptor

GABAA receptors are ligand-gated ion channelsGABA molecules to their binding sites in the extracellular part of receptor triggers opening of a chloride ion-selective poreinhibiting the firing of new action potentials.

GABAB receptors are G protein-coupled receptorsA slow response to GABA is mediated by GABAB receptorsnot dependent on Cl¯