OBI 814 - Estus Lecture 3 - Exam 2

• Somatic (motor) and autonomic nervous systems are two major divisions of the nervous system

Somatic vs Autonomic Nervous System

• These systems differ in the placement of effector neurons
• Somatic nervous system involves CNS neurons only, while autonomic involves CNS neurons acting via peripheral nervous system (PNS) neurons
• Somatic target types are skeletal muscles only but Autonomic target types include smooth/cardiac muscles and glands
• Somatic control is voluntary (except for reflexes), but autonomic control is involuntary
• Somatic motor neuron firing results in muscle contraction
• Autonomic neuron firing results in contraction or relaxation, depending on context

Somatic (Motor) Nervous System

• Motor neurons activate skeletal muscle contraction without direct inhibition
• The site of neuron-muscle interaction is the neuromuscular junction
• Motor neurons release Acetylcholine (ACh) onto nicotinic ACh receptors
• Ligand-gated Na+ channels open in response to ACh
• Na+ influx causes skeletal muscle depolarization, resulting in increased cytosolic Ca+2 via voltage-gated Ca+2 channels and Ca+2 induced Ca+2 release from specialized muscle endoplasmic reticulum (sarcoplasmic reticulum)
• Sarcoplasmic reticulum is a specialized endoplasmic reticulum where Ca+2 acts on SR ryanodine receptors to induce Ca+2 release
• Released Ca+2 is a critical mediator of muscle contraction
• ACh is degraded to acetate and choline by acetylcholine esterase at a rate of 500,000 ACh/sec/molecule enzyme, which is essentially diffusion limited

Spinal Reflexes

• These innate reflexes are the simplest controls of motor function
• They involve involuntary skeletal muscle movement controlled through reflex arcs
• Reflex arcs consist of a sensory neuron, spinal component, and motor neuron
• Voluntary skeletal muscle movement is controlled by the motor cortex in the brain
• Spinal reflexes include myotatic (muscle stretch reflex) and inverse myotatic reflexes

Muscle Sensors

• Muscle status is signaled by muscle spindles and Golgi tendon organs
• Spindles consists of afferent nerve fibers wrapped around intrafusal muscle fibers
• Specialized muscle fibers contribute little to muscle tension
• Nerve fibers signal STRETCH status, found in most skeletal muscles, aiding fine motor control
• Golgi tendon organ (GTO) is a deciduous tree-shaped nerve fiber integrated into the tendon
• GTOs serve as CONTRACTION sensors, increasing firing with change/particularly during isometric contraction
• Spindles are ~100 um wide, up to 10 mm long
• GTOs are ~100 um wide, 1 mm long
• When a muscle is passively stretched, muscle spindle shows increased firing rate with stretch
• Golgi tendon organ shows little to no activity

Myotatic Reflex

• E.g. sustained stretch leads to tonic muscle contraction
• Passive stretch, increasing weight activates muscle spindle afferents
• Spindle nerve axons synapse onto motor neurons directly (monosynaptic) in the spinal cord gray matter
• Motor neuron excitation causes contraction of the stretched muscle
• Other branches of muscle spindle afferents synapse on inhibitory interneurons, which results in inhibition of the antagonist muscles (reciprocal innervation)
• Patellar reflex is another example

Response to Strong Muscle Contractions

• When there's strong muscle contraction, the spindles are quiescent
• GTO neurons fire strongly with contraction

Inverse Myotatic Reflex

• GTO relaxes muscle to avoid damage
• Golgi tendon organ (GTO) neurons increase firing rate with strong muscle contraction
• Afferent GTO fibers synapse on both inhibitory and activating interneurons within the spinal cord gray matter
• Interneurons cause motor neurons to relax the contracted muscle and contract antagonist muscles (reciprocal innervation)
• The reflex protects muscle from damage due to excessive weight/contraction

Circuit Diagram of Inverse Myotatic Reflex

• Extreme muscle contraction activates GTO
• GTO inhibits contraction by relaxing flexor muscle and contracting extensor muscle
• This prevents muscle and tendon damage

Pharyngeal (gag) Reflex

• This reflex is evoked by touching the roof of the mouth, back of tongue, uvula, or back of throat
• It prevents objects from entering the throat, helping to prevent choking
• Sensory limb is predominantly glossopharyngeal nerve
• Effector motor limb is vagal cranial nerve X
• Causes a brisk and brief elevation of the soft palate and bilateral contraction of pharyngeal muscles
• It is of variable sensitivity among people

Autonomic Nervous System

• It is critical for homeostasis ensuring a state of balance among organ systems so the body can survive and function

Autonomic Nervous System: Sympathetic vs Parasympathetic

• Symp pre-ganglionic neurons are thoraco-lumbar (T1-L5), PS are cranial and sacral
• Symp ganglia are located nearer the vertebrae, and PS are near or on targets
• Most tissues innervated by both Symp and PS
• Symp-specific targets include most vasculature and sweat glands, no PS-specific targets
• Autonomic neurons release neurotransmitter onto target using en passant (in passing) synapses, leading to diffuse transmitter release across target surface

Transmitters In Systems

• Sympathetic pathways use acetylcholine and norepinephrine, while Parasympathetic pathways use acetylcholine
• CNS uses ACh
• Autonomic ganglion uses Norepinephrine>Epinephrine and ACh
• cleared from synaptic cleft by acetylcholine esterase – serine in active site is target of organophosphate insecticides
• Peptides can also be released, tend to be longer term modulators
• Some sympathetic ganglionic neurons release Neuropeptide Y (vasoconstrictor) onto targets

Synaptic Vesicles

• Synaptic vesicles have heterogeneity, Chemical neurotransmitters, e.g., ACh, tend to be stored in smaller vesicles while peptides tend to be stored in larger vesicles
• Peptide vesicles tend towards reserve pool, meaning that their greatest release is in response to prolonged stimulation

Symp and PS Receptors

• Primary Ganglionic Receptor for both is Nicotinic ACh Receptor
• Adrenergic Receptors and Muscarinic ACh receptors at Targets
• Have 7 TM, G-protein coupled receptors (GPCR)
• Alpha-Adrenergic: phenylephrine activates
• Beta-adrenergic: isoproterenol activates; beta-blockers (propranolol) inhibit
• Muscarinic AChR: activated by muscarine and inhibited by atropine

Adrenal Medulla

• The adrenal cortex is a true endocrine gland
• The adrenal medulla is a modified sympathetic ganglion
• The chromaffin cell is a modified postganglionic sympathetic neuron
• The hormone produced is Epinephrine, a neurohormone that enters the blood via the adrenal medulla.
• The ratio is about 4:1 epi to norepi

Actions of S/PS

• Actions of the sympathetic and parasympathetic (S/PS) systems when stimulated vary by tissue type and the receptors involved
• Heart
  • PS Stimulation : Decrease Force and Decrease Rate
  • Sympathetic Stimulation: Increase Force, Increase Rate via B1 receptor
• Blood Vessels
  • Skin Little Effect with PS
  • Sympathetic Stimulation to Skin constricts Alpha1 (Epi=NE)
  • Viscera No innervation with PS
  • Sympathetic Stimulation to Viscera constricts Alphal
  • Skeletal No PS innervation
  • Sympathetic Stimulation to Skeletal dilates , B2, some Alpha
• Lung Bronchi Contract
  • Sympathetic Stimulation to Lung relaxes, B2
• GI Tract Increases Motility and Secretions
  • Sympathetic Stimulation to GI tract decreases Motility and inhibits Secretions via Alpha1 alpha1 and B
• Liver has No known effect from Parasympathetic
• Liver has Sympathetic Stimulation by Glycogenolysis B2
• Vision pupil constriction Sympathetic Stimulation by Pupil dilation Alpha
• Sweating has Copious sweating. Sympathetic Stimulation of Muscarinic!!??!!

Autonomic Tone

• Many autonomic neurons maintain slow basal discharge rate, e.g., 1 AP/sec,
• This provides latitude that can be increased or decreased
• Full activation is about 10-20 APs/sec.
• Sympathetic neurotransmitter diffusion from synapse contributes to basal blood levels
• ACh is cleaved by AChE, and little escapes synapse
• Adrenal medulla also has basal release rate into vasculature
• Basal sympathetic tone maintains blood vessels at ~1/2 max diameter

Default State

• Most organs are dually innervated
• Arterioles: Skin/viscera vasodilation, hypotension by default
• GI Tract Reduced tone and secretions for resting
• HUMANs, PS is predominant for most tissues
• Example given is that in mice, sympathetic system is very predominant over parasympathetic system

Autonomic Reflexes: Local Axon Reflex

• Skin injury stimulates sensory nociceptor (these are DRG neurons)
• This causes:
  • "Afferent - towards brain" wave of depolarization up collateral to the axon
  • Then up to "Orthodromic , refers to neurons firing action potentials with prevailing direction" the CNS.
• Depolarization wave also progresses from axon back down other collaterals
• This "Efferent - away from brain" and is "Antidromic -refers to neurons firing action potentials against prevailing direction" and occurs against prevailing direction
• NT includes substance P, vasodilates nearby blood vessels, produces localized reddening of skin
• The local axon reflex is antidromic because an afferent neuron is acting in an efferent fashion

Blood Pressure

• The autonomic nervous system maintains blood pressure via the Baroreflex
• LOW blood pressure DECREASES firing rate of baroreceptors on carotid artery and aorta
• The Medullary cardiovascular inhibits PS neurons and activates Sympathetic neurons
• Blood pressure INCREASES because:
  • Sympathetic ACTIVATION INCREASES HR and contractility
• Sympathetic ACTIVATION constricts skin and visceral vasculature
• PS INHIBITION at heart by vagal nerve INCREASES HR

Increased Blood Pressure

• INCREASING blood pressure dilates blood vessels
• Increased firing rate of baroreceptors causes the medullary center to activate PS and inhibits sympathetic system
  • Increased PS will decrease lowers cardiac output by decreasing HR
• Overall, this combination lowers blood pressure

Fight or Flight Response

• Highly stressful situation activates Sympathetics, especially in adrenal medulla where epinephrine/NE is dumped into blood stream which leads to a set of system responses:
  • Cardiovascular - increased rate and contractility, shift blood flow from skin and viscera to skeletal muscle
  • Respiratory – dilation of bronchioles, and an increased rate
  • Metabolic -Glycogenolysis in liver in order to increase blood glucose sugar
• Also leads to Lipolysis in adipocytes to increase blood free fatty acid as alternative energy source
• In someone with Vasovagal Syncope, fainting may occur during needle injections
• Strong emotional stimulation leads to high sympathetic activity - Baroreflex causes parallel increase in PS in effort to lower blood pressure
• Sudden removal of emotional stress causes rapid decrease in Sympathetics. PS can overshoot
• Results in insufficient blood flow to brain maintain consciousness.

Autonomic Dysreflexia

• A life threatening emergency that Occurs in about 50% of individuals with an injury at T6 or above
• Symptoms include: - Very high blood pressure (can be above 300, pounding headache) - Bradycardia (slow pulse) - Flushed above injury - Cold, pale skin below injury

Etiology of Autonomic Dysreflexia

• Noxious stimuli activate sensory nerves below injury Sensory afferent activation includes firing onto local sympathetic neurons in spinal cord, leading to their activation
• This causes High blood pressure - which is severe vasoconstriction caused by over-active Symp stimulation -Loss of higher negative feedback from higher centers in areas below SCI
• In response Bradycardia will occur as baroreceptors sense high blood pressure, activate PS and inhibit Symp
• CNS control of splanchnic (visceral) sympathetic innervation is lost
• The Treatment for this would be Identify cause of noxious stimuli, blocked catheter, or a pressure ulcer. Blood pressure drops occur with with successful treatment, or a stroke/death