Efferent

From CNS
- nerves carry impulses from CNS
- Somatic (voluntary) nerves
- Autonomic (involuntary) nerves
- sympathetic
- parasympathetic

Nervous Tissue in PNS and CNS is made of:

1. Nerve cells (neurons) - information messengers. Most diverse kind of cells in body
2. Supporting cells (neuroglia) outnumber neurons by up to 9:1
Cells are densely packed so there is little extracellular space

Neuroglia of CNS

1. Astrocytes
2. Microglia
3. Ependymal Cells
4. Oligodendrocytes

Astrocytes

- most abundant glial cells
- outnumber neurons by about 10:1

3 jobs of astrocytes

1. help form a network on which neurons grow
2. anchor neurons to capillaries
3. mop up 'leaked' neurotransmitters

Microglia

- protective role
- sense microbes and debris
- transform into macrophages and phagocytose debris

Ependymal Cells

- line cavities of brain and spinal cord
- are ciliated - to circulate cerebral spinal fluid

Oligodendrocytes

- wrap their branches around large nerve fibers (axons) and create an insulating cover or Myelin Sheath - for up to 60 axons

Neuroglia of the PNS

1. Satellite Cells
2. Schwann Cells

Satellite Cells

- function unknown
- surround neuron cell bodies in ganglia

Schwann Cells

- wrap around large nerves to create a Myelin Sheath
- just like Oligodendrocytes but can only surround 1 axon at a time

Neurons

Cells of nervous systems are neurons
- are ~100 billion neurons in the CNS
- specialized to conduct electrical impulses
- normally 80 times per second
- in epilepsy can fire up to 500 times per second
- last your entire life
- amitotic - do not divide
- very high metabolic rate; need constant supply of glucose and oxygen

Structure of Neurons

- many different shapes
- usually large, complex
- receptive region (dendrites)
- cell body (soma)
- conducting region (axon)
- output region (nerve terminal)

Cell body of neuron

also called the Soma
- contains usual organelles
- nucleus, ribosomes, ER, golgi, mitochondria
- neurofibrils - maintain cell shape and integrity

Nuclei

a cluster of cell bodies in the CNS

Ganglia

a cluster of cell bodies in the PNS

Dendrites

- branching extensions of the cell body
- also contain cytoplasm and organelles
- provide increase in surface area for input signals
- some are 'thorny' - dendritic spines
- transmit incoming information to axon hillock by Graded Response

Axon

- one per neuron
- arises from axon hillock
- short or long (nerve fiber)
- can branch (axon collaterals)
- usually has about 10,000 terminal branches
- is the conduction component of a neuron i.e. transmit impulses
- Terminals are the secretory component (Nt's)
- contains organelles, but NO ER or Golgi
- axon relies on cell body for protein synthesis
- axons decay quickly when damaged

axolemma

plasma membrane of axon

Anterograde

From cell body to terminal
- mitochondria
- replacement molecules for axolemma, NT synthesis
- Transported by the protein kinesin

Retrograde

To cell body from terminal
- molecules and organelles for degradation and recycling
- transported by the protein dynein

Myelin Sheath

- large, long axons are covered in Myelin (fatty protein) that electrically insulates axons
- increases transmission of nerve impulses along axon
- 150x faster than unmyelinated
- Formed by Schwann Cells
- cells wrap themselves around axon many times
- tight coil of wrapped membranes

Node of Ranvier

a gap left between adjacent Schwann cells
axon is exposed at node
axon collateral at node

white matter

myelinated fibers

gray matter

unmyelinated fibers and cell bodies

Structural Classification of Neurons

1. Multipolar
2. Bipolar
3. Unipolar

Multipolar

- 99% of neurons
- numerous dendrites
- 3 or more cell processes

Bipolar

have 2 processes (axon and dendrite)
- rare. found in sensory organs
ex. retina of eye, olfactory mucosa

Unipolar

- 1 process emerges from cell body
- most are sensory neurons in PNS

Nerve Impulses

- neurons communicate with each other by generating nerve impulses
- nerve impulses are electrical currents that travel through neurons.
- in the dendrites and cell body the electrical current is called a GRADED RESPONSE
- in the axon the electrical current is called an ACTION POTENTIAL

Graded Response

a short lived, local change in membrane potential (depolarization). This change causes current to flow that decreases in strength with distance

Action Potential

a large, short depolarization event that does NOT decrease in strength with distance. They occur only in axons, sarcolemma and T-tubules

Why the difference between AP and GR?

1. the dendrites and cell body have chemical and/or mechanical gated ion channels
2. The axons, sarcolemma and T-tubules have voltage gated ion channels

How do you get electrical current to flow?

First, all plasma membranes must be polarized at rest.
- that means there is a voltage difference across membrane

Why is there a voltage difference between the inside of the membrane and the outside?

- Because there are leaky ion channels sprinkled all over the membrane of the neuron
- therefore, more positive ions (K+) leak out of the cell then leak back in (Na+).

Leaky Ion Channel

allows K+ to leak out of the cell easier than Na+ can leak back into the cell

Sodium/Potassium pump

pumps out 3 positive ions (Na+) for every 2 it pumps in (K+)

The net effect is;

more positive charges collect on the outside surface of the cell membrane than the inside surface creating a voltage difference of -70mV, called the Resting Membrane Potential

Resting Membrane Potential

Inside cell is more negative than outside (-70mv)
- called a polarized state
- occurs ONLY at membrane
- cytoplasm is neutral
- extracellular space is neutral

So what is depolarization?

- a change in Resting Membrane Potential such that the inside now becomes more positive than it was when at rest

Signal Conduction along nerves

- information is carried by nerves in the form of electrical current

2 forms of electrical signals

1. graded respons
2. action potential

graded response (detail)

- occur at sensory receptor endings and dendrites
- produced by a stimulus
- are short lived, local changes in RMP
- cause electrical current flow that DECREASES with distance
- magnitude of change in membrane potential is related to magnitude of stimulus

Mechanism of a graded response

1. A small region of membrane becomes depolarized
2. At point of stimulus inside of cell has the charge
3. positive charge will flow laterally (attracted to negative charge)
- Outside cell positive charges flow to less positive region created by depolarization
- the greater the initial depolarization the greater the currents
- as positive charges move laterally the membrane becomes depolarized
- this effect becomes weaker and weaker the further the current travels from site of initial stimulus

action potential (detail)

- generated by excitable tissue i.e. nerves and muscle cells
- are brief reversals of membrane potential
- change in amplitude is by about 100mv (never changes)
- takes about 3 milliseconds (never changes)
- is an all-or-none event
- voltage change travels along axon/sarcolema/t-tubules
- in a neuron the traveling voltage change is called a nerve impulse

profile of the voltage changes

1. RMP ~ -70mv
2. a depolarization sufficient to reach threshold
Once threshold is reached the depolarization is self-perpetuating
- no further stimulus required
- polarity is reversed. inside now more positive than outside
3. repolarization phase (neuron refractory)
4. after hyper-polarization
- neuron are refractory (will not respond)

Ionic Basis of action potentials

1. RMP generated by Na+/K+ pump. Deficit of the positive ions inside cell. RMP ~ -70mv. Na+ and K+ channels closed
2. Voltage gated Na+ channels open causing depolarization fo membrane. At -55mv local depolarization is sufficient to spread along membrane opening more voltage gated Na+ channels
More Na+ enters --> membrane depolarizes further till all Na+ channels open
- before AP peaks - Na+ channels begin to close
- inside of cell begins to repel further entry of Na+
- AP peaks - net influx of Na+ stops
K+ gates open. K+ exits cell i.e. positive ions exit cell. Returns inside cell to negativity (Repolarization)
3. K+ gates are to slow to close causing excessive K+ efflux leading to an after hyperpolarization or undershoot

_________ restores resting electrical conditions but _______________ are returned by 'reving' up Na+/K+ pump

Repolarization; ionic distributions

Refractory period

from the opening of the Na+ channels to the resetting of the Na+ channels. The neuron cannot respond to another stimulus while in this phase

Propagation of an action potential

- action potentials are propagated (transmitted) along the entire length of the axon
- the influx of Na+ establishes a current that depolarizes adjacent membrane areas
- flow of current is unidirectional as no current will flow in a refractory region

Speed of Nerve Impulses

- skeletal muscle - faster in nerves
- gut, glands - slower in nerves

Speed of conduction is determined by:

1. axon diameter
2. myelination

axon diameter

larger diameter axon means less resistance to flow of ions which means membrane reaches threshold faster and impulses travel faster

Myelination

in unmyelinated nerves AP's are generated next to each other - one after another - continuous conduction
In myelinated nerves AP's occur ONLY at node of Ranvier
- no Na+ channels under myelin sheath
- current flows under myelin from node to node so nerve conduction of impulses is faster
- called saltatory conduction

Classification of Nerve fibers (axons)

1. group A
2. group B
3. group C

Group A

mostly sensory and motor fibers serving:
- skin
- skeletal muscles
- joints
Have:
- large diameter, thick myelin sheaths
- speed of conduction is up to 300 mph

Group B

Autonomic Nervous system sensory and motor fibers
- small somatic sensory fibers (pain and small touch fibers)
- are medium diameter
- lightly myelinated
- speed of conduction is 40 mph

Group C

Same fibers as group B
- small diameter
- unmyelinated
-no saltatory conduction
- speed of conduction is 2mph

Pathologies of the Nervous System

1. Multiple Sclerosis
2. Amyotrophic Lateral Sclerosis (ALS)

Multiple Sclerosis

- an autoimmune disease
Symptoms - poor vision
- poor muscle control:
- clumsiness
- weakness
- paralysis
Immune system makes antibodies to myelin so there is destruction of myelin sheath which leads to slow impulse conduction
- Leakage and short-circuting of electrical current
- eventually impulse conduction stops

Amyotrophic Lateral Sclerosis (ALS)

- Lou-Gehrig's Disease
- Motor NEuron Disease
- Degeneration of motor nerves - Sporadic 90-95% of cases - familial 5-10% of cases
Familial cases have mutation in gene for SOD1 - no protection from free radicals

Electrical to chemical signaling

- nerve impulses travel along Motor Neurons
- end of axon branches forms a Neuromuscular Junction (NMJ) with a single muscle fiber
- NMJ - motor nerve ending (terminal)
- synaptic cleft
- motor end plate

Nerve Terminal

- contains synaptic vesicles (sacs containing neurotransmitter).
A NEUROTRANSMITTER (NT) is a chemical message.
At the NMJ the NT is Acetylcholine (Ach).

Synaptic Cleft

- is a gap between nerve terminal and sarcolemma

Motor End Plate

A dimple in the sarcolemma
- junctional folds of sarcolemma
- Ach receptors
- transmembrane proteins that bind Ach
- transmit chemical signal into electrical signal

Mechanism of Nerve Terminal

1. Nerve impulse travels down axon
2. Impulse reaches nerve terminal
3. voltage gated Ca2+ channels open
4. Ca2+ flows into nerve terminal
5. Ca2+ fuses with synaptic vesicles
6. Synaptic vesicles fuse with terminal membrane (presynaptic membrane)
7. Exocytosis of Ach into Synaptic Cleft
8. Ach diffuses across synaptic cleft
9. Ach attaches to Ach Receptors on postsynaptic membrane
10. Ach Receptors trigger depolarization of Sarcolemma
11. Depolarization Spreads to T-Tubules
12. Causes Ca2+ binds toponin ... etc

How is signal terminated?

1. decrease nerve impulses
2. Acetycholinesterase in synaptic cleft degrades Ach
- most rapid mechanism
- lifetime of Ach in Synaptic Cleft ~ 200 microseconds
In some cases the neurotransmitter (e.g. Dopamine) is recycled by the nerve terminal

Pathologies

Myasthenia Gravis
- muscle weakness
- difficulty swallowing
- drooping eyelids
Autoimmune disease
- immune system developed antibodies to Ach Receptors
- Ach receptor number is low

Tubocurarine (curare)

Botanical agent from S. America
Binds to Ach R's
Prevents Ach from binding
Causes muscular paralysis
used as a muscle relaxant during surgical anesthesia

Anticholinesterases

drugs that inhibit (block) acetylcholinesterase (AchE)
Ach does not degrade
too much Ach in Synaptic cleft leads to excessive stimulation of Ach R's and leads to muscle paralysis
Phsostigmine
Insecticides - parathion, malathion (organo phosphates)
Nerve gases (organo phosphates) - sarin, tabun, soman and VX (kills within minutes)

Medicinal Uses

to increase tone in smooth muscle of GI tract and bladder
- myasthenia gravis

tetrodotoxin

- one of the most potent poisions known
- found in fugu (Japanese) or puffer fish
- block Na+ channels in skeletal muscle
- cell cannot depolarize
- death is by paralysis of respiratory muscles

Botulinus Toxin

BOTOX
- from bacteria Clostidium Botulinum
- block Ach release from nerve terminal
- paralysis of muscles

Local Anesthetics

- procaine, lidocaine, cocaine
- prevent conduction of nerve impules
- block Na+ channels

Synapses and Neurotransmitters

- synapses release and receive NT's
- NT's act at Receptors to open or close ion channels and cause changes in membrane permeability

A synaps has 2 parts:

1. Nerve terminal - contains synaptic vesicles that fuse with presynaptic membrane to exocytose NT's into synaptic cleft
2. A receptor region - an area of the postsynaptic membrane with specific neurotransmitter receptors

Excitatory Synapses

- NT release causes depolarization or postsynaptic membrane
- These Graded depolarizations are called Excitatory Postsynaptic Potentials (EPSP's)
- if enough EPSP's are produced an AP will be triggered at axon hillock

Inhibitory Synapses

- NT release induces hyperpolarization of postynaptic membrane
- these graded hyperpolarizations are called Inhibitory Postsynaptic Potentials (IPSP's)
- if enough IPSP's are produced generation of AP's at the axon hillock will be prevented

Neurotransmitters

to date there are over 50 NT's
most neurons make 2 or more NT's
neurons can release one or all NT's

Classification of NT's

NT's are classified based on chemical structure
1. Acetylcholine (Ach)
2. Biogenic Amines
3. Amino Acids

Acetylcholine (Ach)

- released at NMJ - excitatory
- degraded by AchE

Biogenic Amines

Dopamine, norepinephrine, epinephrine (adrenalin), serotonin, histamine

Amino Acids

Inhibitory - Gamm AMinobutyric Acid (GABA)
Excitatory - Glycine, Aspartate, Gluatmate

Smooth Muscle

found in the walls of hollow organs (except the heart)

Smooth muscle cells

- spindle shaped
- one central nucleus
- much smaller than skeletal muscle cells
- endomysium located between muscle fibers
- muscle cells arranged in sheets
- sheets found in all hollow organs except capillaries

arrangement of muscle cells

- two sheets of smooth muscle found in most organs
1. longitundinal layer
2. circular layer

longitudinal layer

- one sheet runs parallel to long axis or organ
- contraction --> dilation --> shortening

circular layer

- fibers run around circumference of organ
- contraction --> constriction --> elongation

Peristalsis

alternating contraction/relaxation of muscle sheets

Also contractions occur in:

Bladder
Uterus
Rectum
Bronchi --> asthma
Stomach --> cramps

Main characteristics of smooth muscle

no NMJ
innervated by autonomic nerves
- have varicosities
- wide synaptic cleft
- called diffuse junctions
- less developed SR
- no T-tubules
- Plasma membrane pouches CAveoli - stores Ca+
Caveoli and SR provide Ca2+ for contraction
- no stiations (no sarcomeres)
- do contain thick and thin filaments
- arranged diagonally
- therefore contract like a slinky
Have non-contractile intermediate filaments- to resist tension

The Brain

Adult Brain Regions - named from embryological development
Brain forms from neural tube (day 26)

Neural Tube

Anterior (rostral)
Posterior (caudal)

Primary Brain vesicles

forebrain
midbrain
hindbrain

Secondary Brain Vesicles

Telencephalon
Diencephalon
Mesencephalon
Metencephalon
Myelencephalon

Adult brain structures

Telencephalon - Cerebrum: cerebral hemispheres (cortex, white matter, basal nuclei)
Diencephalon - Diencephalon (thalamus, hypothalamus, epithalamus), retina
Mesencephalon - Brain stem: midbrain
Metencephalon - Brain stem: pons; Cerebellum
Myelencephalon - Brain stem: medulla oblongata

Adult Neural Canal Regions

Telencephalon - lateral ventricles
Diencephalon - third ventricles
mesencephalon - cerebral aqueduct
Metencephalon - 4th ventricle
Myelencephalon - 4th ventricle

General Organization of the brain

1. Outer layer (cortex) - Gray matter (neuronal cell bodies)
- Covers cerebral hemispheres and cerebellum
2. Below cortex is white matter (myelinated axons)
3. Deeper in brain are islands of gray matter - called nuclei
4. Nuclei surround ventricles of brain

Ventricles

Are hollow chambers filled with cerebrospinal fluid (CSF)
- Two lateral ventricles
- One deep in each hemisphere
- connect to the third ventricle by interventricular foramen of Monroe
- One third ventricle
- connects to fourth ventricle by cerebral aqueduct
- one fourth ventricle
- continuous with central canal of spinal cord
- have 3 openings (apertures)
2 lateral apertures
1 medium aperture