Chapter 6 Neural signaling and structure of the nervous system

Section A. Neural Tissue

1. Nervous system (Nervous System)
Central N.
-Brain and spinal cord
Peripheral N.
2. Neural tissue
1) Nerve cell (Fig. 6-1)
A. Structure
(1) Soma (cell body)
Contains nucleus and organelles
Collection of RER and free ribosomes (Nissl bodies)
(2) Dendrites
Receive incoming signals
(3) Axon hillock (initial segment)
Trigger zone
Generates electric signal
(4) Axon
Transmit outgoing signals
(5) Axon (synaptic) terminal
Send neural signal to other cells- Releasing neurotransmitters
(6) Myelin Sheath (Fig. 6-2)
Layered coverings of axons
a. By oligodendrocytes
CNS
One oligodendrocyte covers multiple number of neurons
b. By Schwann cells
PNS
One cell forms one myelin
(7) Node of Ranvier
Axon where no myelin sheath present
Na+ channels are concentrated
(8) Axonal transport (Fig.6.3)
Cytoskeleton (microtubule)
Motor proteins:
(a) Kinesins: Anterograde movement
From cell body to axon terminal
Movement of nutrients, enzymes, organelles
(b) Dyneins: retrograde movement
From Axon terminal to cell body
Movement of recycled membrane vesicles, growth factors, chemical signals
Directly affects neuronal morphology, biochemistry, connectivity
Sometimes provides a route for foreign substances including toxins and viruses
(9) Synapse (Fig.6.4)
Junctions between two neurons

Presynaptic neuron vs. postsynaptic neuron

Usually between axon terminal and dendrites
2) Neuroglia (Fig. 6.6;Neuroglial cells)
A. Functions
(1) Provides a supporting framework
(2) Phagocytosis
B. Types of glial cells
(1) Astroglia
Largest and dominant neuroglia
Secrete chemicals- neurotransmitters, growth factor
Metabolic functions - provide glucose and remove ammonia
Create a structural framework for the CNS
Perform repairs in damaged neural tissues
(2) Oligodendrocytes
Form myelin sheaths around axons (CNS)
(3) Microglia
Smallest and rarest among neuroglia
Phagocytic cells
(4) Ependymal cells
Formation of ependyma - line the central canal of the spinal cord, and ventricles of the brain
Ependyma (at a certain area) produces CSF
Sometimes ependyma has cillia to facilitate CSF circulation
(5) Schwann cells (only at PNS)
Form Sheath of Schwann (myelin)
Improve impulse conduction
3. Structural class of neurons (structure of neurons)
1) Multipolar neuron
Many dendrites and one axon extending from the cell body
All the motor neurons connecting skeletal muscles are multipolar
*Multipolar interneurons
Short axon
Neural integration between interneurons
Major type of neuron
2) Unipolar neuron
Dendritic and axonal process are continuous
Action potential begins from base of dendrites
Most of the afferent neurons: Receptors of skin, internal organs, muscle
3) Bipolar neuron
Two processes (dendritic and axonal) at either end, and soma in between afferent neurons of
visual and auditory neurons
Axon is relatively short
4. Functional class of neurons (Fig. 6.3; Table 6.1,Fig.6.37)
1) Afferent neurons
Relay sensory information to CNS
Sensory receptors: Somatic and visceral sensory receptors
No dendrites

2) Efferent neurons
Carries motor commands to muscle and glands (effectors)
(1) Somatic nervous system (SNS)
Provides voluntary control over skeletal muscles
(2) Visceral motor system (Autonomic nervous system: ANS)
Provides involuntary regulation of smooth muscle, cardiac muscle, and glandular secretion.
(3) Interneurons
Connect neurons within CNS
Integrator/ signal changer/ gate keeper
99% of neurons
Section B. Membrane potentials
1. Definitions (Table 6.3)
(Membrane) potential: Electric potential difference across plasma membrane (Fig. 6.8a)
Equilibrium potential: The voltage difference across membrane due to a specific ion
concentration gradient
Example: K+ channel (Fig. 6.10)
Resting membrane potential: Potential difference under resting (stabilized) condition (Fig. 6.8b)
*K+ and Na+ quilibrium potential vs. resting potential (Fig.6.12)
2. Resting membrane potential
1) Characters
(1) Relative inside voltage to outside
(2) No electric signal is produced
(3) Na+ and K+ are major components on membrane potential
(4) -40 to -90mV
2) Resting potential determining factors (Fig.6.13)
(1) Specific ion concentrations by Na/K pumps
Na+ : Higher outside
K+: Higher inside
(2) Membrane permeability
Leaky K+ channels, but not on Na+ channels
(3) Population of Na+ and K+ channels
About 50-70% higher K+ channels than Na+ channels
(4) No Cl- pump on cell membrane (only channels)
(5) Proteins and phosphate compounds contribute to the negativity of inside of the cells
3) Calculation of equilibrium potential
(1) Concentration of major ions of a nerve cell (Table 6.2)
(2) Nernest equation
*Only one ion is considered
E= 60 log C0/ C1
C1: intracellular concentration of the ion
C0: Extracellular concentration of the ion
60: constant value
+
K equilibrium potential: -90mV
Na+ equilibrium potential: +60mV
(3) Goldman equation

Multiple ions are considered at a time

*Resting potential: -70mV
4) Cause of resting membrane potential
K+ channel is chiefly permeable (leaky K+ channels)
Small number of Na+ channels
-About 50-70 times higher K+ channels than Na+ channels
3. Graded potentials and action potentials
*Important terms (Table 6.3)
1) Comparison between graded and action potentials (Table 6.4)
A. Graded potential (Fig. 6.16)
(1) Potential changes affect only a limited portion of the cell membrane.
(2) Depolirization or hyperpolarization
(3) Variable amplitude and duration
(4) Decremental (Fig. 6.15)
(5) No threshold or refractory period: summation is possible
(6) Examples: synaptic potential, receptor potential, and pacemaker potential
(7) Occurs at the gland tissues
B. Action potential
(1) All-or-none principle applied
(2) No summation
(3) Has threshold and refractory period
(4) No decrease in intensity through conduction
(5) Only depolarization
(6) Rapid and large change in membrane potential
(7) Deliver stimulus to long distance
(8) "Excitability": Excitable membranes in nerve, muscle, endocrine, immune, and
reproductive cells
2) Shift of potentials (Fig.6.14;action potential)
Depolarize
Overshoot
Repolarize
Hyperpolarize
3) Ionic basis of action potential (Fig. 6.19)
(1) Resting potential
Leaky K+ channels and some Na+ channels
Close to K+ equilibrium potential
Stimulation opens voltage-gated Na+ channels initiates depolarization
(2) Threshold potential
Permits more Na+ channels to open
Na+ influx exceeds K+ efflux
Positive feed back to bring in more Na+ by voltage-gated Na+ channels
(3) Overshoot
Membrane potential changed into positive
Action potential reaches to +30mV
(4) Peak of action potential
Na+ channels closed by inactivation process (Fig. 6.19a)

-"Hinged lid" or "ball and chain"

-Involved protein has side chain of arginine, n-propylguanidinium (nPG)
Voltage-gated K+ channels opened
(5) Repolarization
Rapid drop of action potential due to influx of K+ from opened K+ channels
(6) Hyperpolarization
Due to delayed closure of voltage-gated channels
(7) Restoration of resting potential
Na+/K+ pump
*Tetrodotoxin (puffer fish), and local anesthetics (procaine, lidocaine) bind to the sodium
channel blocking the passage of action potential
*Threshold potential
Membrane potential to which excitable membrane must be depolarized to initiate an action
potential
Usually 15mV less negative than resting membrane potential
*All-or-none principle (Fig. 6.21)
Action potential occur maximally or not at all, but not in between
Single action potential does not show intensity of stimulus
*Threshold stimulus
*Subthreshold potential
*K+ concentration and action potential propagation (K-action potential)
Hypokalemia
-Lower resting membrane potential
-Need stronger stimulation to propagate action potential
Hyperkalemia
-Increase resting membrane potential
-Weak stimulation may cause propagation of action potential
4) Refractory period
(1) Absolute refractory period
While potential stays above the threshold potential level
During action potential, stimulus doesn't produce another action potential
Due to opening and inactivated voltage-gated Na+ channels
(2) Relative refractory period
Second action potential is produced with only greater stimulus than the usual
During hyperpolarization period
Due to lingering inactivation of the Na+ channels, Increased K+ channel openings
(3) Functions of refractory period
Limits the number of action potentials in a given time
Rate of action potential relays intensity of stimulus
Up to 100 action potentials per second
5) Action potential propagation (Fig.6.22)
(a) Moves to adjacent membrane by ion flow
(b) Due to rich voltage-gated Na+ channels and positive feedback of Na+ channel opening
(c) Unidirectional in nerve, bidirectional in muscle
(1) Velocity of action potentials

-Depends on diameter of neuron and myelin sheath presence

-Lager neuron propagates faster
: Less resistance to local current
: Higher ion movement rate in a short time
(a) Unmyelinated axon
Continuous conduction of action potential side by side
The conduction rate is relatively slow (0.5m/sec)
Action potential moves with the cable properties through the axon
(b) Myelinated axon (Fig. 6.23)
Saltatory conduct node to node (leap)
Large and myelinated axon: 100m/sec
Action potentials are occur only at the node
Na+ channels are highly concentrated at the node
Metabolically cost effective less energy needed for ion restoration
* Demyelination
Progressive destruction of myelin sheaths
Caused by inflammation, axon damage, scarring of neural tissue
Gradual loss of sensation and motor control
Regional paralysis and numb
Ex) Multiple sclerosis
Optic nerve, brain, and spinal cord are affected
Partial loss of vision, problems with speech, balance, and general
motor coordination
6) Initiation of action potentials
Graded potentials from receptor potential, or pacemaker potential, or
synaptic potential
Section C. Synapses
Definition: Anatomically specialized junction between two neurons, at which the electrical activity
in one neuron influences the others
1. Ways of neuronal communications (Fig. 6.24, neural circuits)
1) Conversions
Many presynatic and one postsynaptic neuron
Information from many source into one cell's activity
Collecting information
2) Diversions
One presynaptic neuron into many postsynaptic neuron
One information to many pathways
3) Parallels
4) Reverberating circuit
Feedback communication
2. Functional anatomy of synapses
1) Electric synapse
In gap junction between two neurons
Direct movement of action potential to next neuron
Useful when a group of muscles need to move at the same time

Abundant in cardiac and smooth muscle

Rare in general
2) Chemical synapse (Fig.6.25,26)
A. Synaptic vesicle
Released from axon of presynatpic neuron
Contains neurotransmitters
Exocytosis of neurotransmitters
B Synaptic cleft
10 - 20 nm space between two neuron in synapses
Neurotransmitter are released
C. Vesicle docking site
Fuse with synaptic vesicle
D. Receptors
Located in postsynaptic neuron
Bind to neurotransmitters
Open or close ion channels of postsynaptic membrane
3. Mechanisms of neurotransmitter release (Fig.6.27)
(1) Arrival of action potential opens Ca+ channels on axon terminal
(2) Ca+ influx triggers formation of fusion complex between synaptic vesicle and presynatic
membrane (vesicle docking site)
Activation process
(a) Released Ca+ binds to calmodulin
(b) Ca+-calmodulin biding activates protein kinase
(c) Protein kinase phosphorylates synapsin in vesicle membrane
*During inactive state, synapsin holds vesicle to inhibit from presynaptic membrane
binding.
(d) Vesicle fuses with presynaptic membrane
*SNARE proteins (soluble N-ethylmaleimide-sensitive-factor attachment protein
receptor)
-Proteins involved in neurotransmitter release
(3) Exocytosis of neurotransmitter
(4) Neurotransmitter binds to postsynaptic receptor proteins
4. Activation of postsynaptic cell
Binding of neurotransmitter and receptor changes function of ligand-gated channels
1) Fate of neurotransmitters
Reuptaken by active transport into presynaptic terminal
Diffuse away to other area
Destroyed by cholinesterase
2) Responses of chemical synapses (Fig.6.30)
(1) Excitatory chemical synapses (Fig. 6.28)
Activation of receptor opens Na+ channels
Produce graded potential called "Excitatory Postsynaptic Potential"(EPSP)
Elevates activation threshold
(2) Inhibitory chemical synapses (Fig. 6.29)
Activation of receptor opens Cl- channels (or K+)
Produce hyperpolarizing graded potential called "Inhibitory

Postsyanptic Potential"(IPSP)
Stabilize/ decrease membrane potential
(3) Comparison of excitatory and inhibitory synapsees (Fig.6.32)
5. Synaptic integration
- Summation of graded potentials toward initiation of action potential (Fig. 6.31)
Temporal summation
Stimulation on the same cell with intervals
Spatial summation
Multiple stimulation on the same cell at different locations
Initiation segment (Axon Hillock) has low threshold
*Postsynaptic potentials last long time to initiate multiple action potentials
6. Factors that determine synaptic strength (Table 6.5)
1) Presynaptic factors
(1) Availability of neurotransmitter
(2) Axon terminal membrane potential
(3) Calcium concentration
(4) Activation of membrane receptors on presynaptic terminal
a. Axo-axonic synapse (Fig. 6.33)
b. Autoreceptors (negative feedback)
(5) Drugs or diseases influence on presynaptic factors (Fig. 6.34)
Causes
a. Leakage of neurotransmitter from vesicle (exposure to enzyme)
b. Increase transmitter release
c. Block transmitter release
d. Inhibit transmitter synthesis
e. Block transmitter reuptake
f. Block transmitter digesting enzyme at cleft
g. Bind to postsynaptic receptors -Agonists or antagonists
h. Inhibit or activate second messenger activity in postsynaptic cell
2) Postsynaptic factors
(1) Immediate past electrical history
(2) Effects of other neurotransmitters/ modulators
(3) Drugs and diseases (h of Fig. 6-34)
3) General factors
(1) Area of synaptic contact
(2) Enzymatic destruction of neurotransmitter
(3) Geometry of diffusion path
(4) Neurotransmitter reuptake
7. Neurotransmitters and neuromodulators (Table 6.6)
1) Neuromodulators are,
(1) Complex responses in postsynaptic cells
(2) Associated with slow events (learning, development, sensory)
2) Classes of neurotransmitter/neuromodulator
(1) Acetylcholine (ACh)
Major neurotransmitter in PNS and brain
Choline + Acetyl CoA.

Synthesized from presynaptic vesicles

Binds to cholinergic receptor
-Nicotinic (cause of Alzheimer's disease), muscarinic receptor
(2) Biogenic amines
From amino acids
Catecholamines -Dopamine, norepinephrine, epinephrine
From tyrosine (Fig.6.35)
Norepinephrine is a major neurotransmitter in PNS and CNS
Adrenergic / noradrenergic fibers
Roles in consciousness, mood, motivation, blood pressure regulation, and hormone release
Serotonin
From tryptophan
Roles in sleep, food intake, reproductive behavior, emotional states
Histamine
Released from mast cells and basophils
Local immune responses and vasodilation
(3) Amino acid transmitters
Glutammate (Fig.6.36), aspartate
GABA (Gama-Aminobutyric Acid), glycine
(4) Neuropeptides
Endogenous opioids -endorphin, dynorphins
Peptide P
(5) Miscellaneous
NO (Nitric Oxide) -from arginine
ATP
Section D. Structure of the nervous system
1. Central nervous system (CNS)
1) Brain (Fig. 6.38, Table 6.7)
Major divisions of the brain
A. Cerebrum (Fig.6.39)
Largest portion of the brain
Weighs about 1200g in female and 1400g in male
Brain size is related to body size no relationship with intelligence
Divided into two hemispheres, connected by longitudinal fissure
Center for conscious thought processes, sensations, intellectual functions, memory storage
and retrieval, and complex motor patterns
B. Diencephalon
Part of forebrain
Contains thalamus, hypothalamus, and pituitary gland
A key relay zone of sensation and movement
Control mechanisms for homeostatic integration
(1) Thalamus
Comprise about 4/5 of diencephalon
Most part of the walls of the third ventricle
Relay center through which sensory information passes to the cerebrum

(2) Hypothalamus
Located below the thalamus
Floor and lateral wall of the third ventricle
Neural center for hunger, thirst, and body temperature regulation
Controls pituitary gland secretion
Regulation of sleep, sexual desire, and emotions
Secretes hormones Antidiuretic hormone (ADH) and Oxytocin through pituitary gland
(3) Pituitary gland
Located below the hypothalamus
Connected to diencephalon body by stalk called infundiburum
Divided into anterior and posterior pituitary gland
Secretes pituitary hormones
C. Brainstem
(1) Midbrain
Located above the pons and below the thalamus
The uppermost part of the brainstem
Process visual and auditory information
Generate involuntary motor responses
Maintenance of consciousness
(2) Pons
Rounded bulge on the underside of brain
Located between midbrain and medulla oblongata
Bridge connects cerebellum to the brain stem
Regulates respiration
(3) Medulla oblongata
Segment attached to the spinal cord lowest subdivision of brain stem
Passage of information from and to the brain
Has group of neurons called vital centers
-Vasomotor center: controls peripheral blood flow
-Cardiac center: controls heart rate
-Respiratory rhythmicity center: basic pace of respiratory movement
D. Cerebellum
Occupies the inferior and posterior aspect of the cranial cavity
The second largest structure of the brain
Connected with cerebrum, pons, medulla oblongata, and spinal cord
Receives input from joint, tendon, and muscle receptors
Participates in the coordination of movement
Damage of cerebellum produces ataxia
-Lack of coordination due to errors in the speed, force, and direction of movement
*Limbic system (Fig. 6.40)
A functional system
Consisted with frontal lobe cortex, temporal lobe, thalamus, and hypothalamus
Associated with learning, emotional experience/ behavior, and endocrine functions
2) Spinal code
Passage of sensory impulses to the brain and motor impulses from the brain
Controls spinal reflexes

A. Nomenclature of nerve fibers in spinal cord

Ascending sensory fiber tracts
-Start with the prefix spino- and end with the name of the brain region where the spinal
cord fibers first synapse (ex: spinothalamic tract)
Descending motor fiber tracts
-Start with a prefix denoting the brain region that give rise to the fibers and end with the
suffix -spinal (ex: corticospinal tract)
B. Anatomy
(1) Consists of 31 segments (Fig.6.42)
Cervical spinal nerves: 8 segments
Thoracic spinal nerves: 12 segments
Lumbar spinal nerves: 5 segments
Sacral spinal nerves: 5 segments
Coccygeal nerve: 1 segments
(2) Every segment has a pair of dorsal root ganglia and ventral roots (Fig.6.41)
a. Dorsal root ganglia
Contain cell bodies of sensory neurons
Bring sensory information to the spinal cord
b. Ventral roots
Contain the axons of CNS motor neurons
Control muscles and glands
c. Spinal nerve
Mixed nerve -Dorsal and ventral roots united
(3) Spinal cord runs up to L2
(4) Cauda equina
Contains long ventral and dorsal roots inferior to tip of spinal cord
2. Peripheral nervous system (PNS)
1) Consists with cranial nerves and spinal nerves
(1) Cranial nerve (Cranial N; Table 6.8)
Arising from the brain
12 pairs
Mixed nerves of sensory and motor fibers
(2) Spinal nerves (Spinal N A, B)
Arising from the spinal cord
31 pairs
Mixed nerves of sensory and motor fibers
2) Divisions of peripheral nervous system (Table 6.9)
A. Afferent division
Sensory input to CNS
B. Efferent division (Fig.6.43)
Signal from CNS to effectors
Neurotransmitters (Fig.6.46)
-First neurotransmitter from the nerve exiting CNS is always Ach.
(1) Somatic division
Signal to skeletal muscle
Leads to muscle contraction

(2) Autonomic division (Fig. 6.44)

Signal to glands, cardiac and smooth muscle, and gastrointestinal tract
Excitatory or inhibitory
Examples of autonomic nervous systems activity (Table 6.11)
a. Sympathetic pathway
"Fight-or-flight"
Nerves from thoracolumbar division
b. Parasympathetic pathway
"Rest-or-digest"
Nerves from brain and sacrum (craniosacral division)
3. Blood Brain barrier
1) Function
Protects from harmful substances through blood including pathogens
2) Formation
-Form a tight junction among,
Endothelial cells
Astrocytes' secretion (determines permeability)
Basement membrane of blood vessels
3) Permeability of the barrier
a) Type of substance transport
Facilitated diffusion: creatinine, urea, ions...
Active transport: glucose, proteins
b) Lipid-soluble substances move freely
Oxygen, carbon dioxide, alcohol, caffeine...
c) Protein and antibiotics are carried by transporters
4. Cerebrospinal fluid (CSF)
1) Functions
(1) Physical protection of brain and spinal cord
(2) Chemical protection
Maintains ionic balance
(3) Exchange of nutrients and wastes
2) Ventricles (Fig.6.47)
CSF containing cavities in brain
Four ventricles
-Two lateral ventricles
-Third ventricle
-Forth ventricle
3) CSF production
From choroid plexuses of ventricles
-Network of capillaries in the walls of ventricles
Filtration of plasma and secretion through ependymal cells
4) Circulation of CSF (subarachnoid space)
Openings in the roof of fourth ventricle
Subarachnoid space contains CSF
Reabsorption of CSF into blood
-Through arachnoid villi at suprior sagital sinus

Active circulation
-Forces from production of CSF
-Circulatory, respiratory, and postural pressures