Nervous Tissue Chapter 12

Nervous Tissue

Chapter 12

• Overview of the

Nervous System

• Cells of the Nervous

System

• Electrophysiology of

Neurons

Subdivisions of the Nervous System

Two major anatomical

subdivisions:

• Central Nervous System

(CNS)

– the brain and spinal cord

• Peripheral Nervous

System (PNS)

– nerves and ganglia outside

of the CNS. (Ganglia are

clusters of neurons)

• Sensory (Afferent) Division brings visceral (thoracic

and abdominal organs) and somatic (skeletal muscle,

skin, bone and joints) sensory information into the CNS

• Motor (Efferent) Division sends out information from

the CNS.

– visceral motor division (Autonomic NS) innervates

cardiac muscle, smooth muscle, glands

• sympathetic division (active, arousing responses)

• parasympathetic division (calming, maintenance

functions like digestion)

– somatic motor division innervates skeletal muscle

• voluntary movement of skeletal muscles

Types of Neurons

• Sensory Neurons (afferent neurons)

– receptors that detect changes in the external

environment and within the body (temperature,

pressure, vibrations, light, chemicals)

– this information is transmitted into brain or spinal

cord

• Interneurons (association neurons)

– positioned between sensory neurons and motor

neurons in the CNS

– 90% of human neurons are interneurons

– interneurons process, store and retrieve information

• Motor Neurons (efferent neurons)

Characteristics of Neurons

• Excitation (irritability)

– cells respond to changes in the body and external

environment (the cells respond to stimuli)

• Conduction

– cells produce signals that travel from cell to cell

• Secretion

– when a signal reaches the end of an axon, a

chemical neurotransmitter is released

Structure of a

Neuron

Axon Hillock Initial Segment Dendrites Nissl (clumps of RER) Schwann Cells Axon Terminal Arborization Nodes of Ranvier Terminal Bouttons Cell Body (Soma)

Dr. Franz Nissl (1860-1919) was born in Germany, he gravitated to medicine and as a student in

Munich he wrote on pathology of cortical cells in which he used a stain he created which opened up a new era in neurocytology and neuropathology. Nissl Granules brought out by basic aniline stains perpetuate his name."But he also did outstanding work in psychiatry and demonstrated the correlation of nerves and mental disease by relating them to changes in glial cells, blood elements, blood

vessels, and brain tissue in general. He worked with

Alzheimer on general paresis. In the last 10 years of his life he did studies in which he established connections between the cortex

Axon

Hillock

Neuron Morphologies

• Multipolar Neuron – many dendrites – one axon that

may brach – most common type of neuron • Bipolar Neuron – one dendrite – one axon – olfactory, retina, inner ear • Unipolar Neuron – only one process

comes off soma – also called

pseudounipolar neurons

– sensory from skin and organs to

Neuroglia

• Neuroglia are cells other than neurons in the nervous system (90% of cells in the CNS are glia, but they only account for 50% of the volume of the CNS).

• Many Schwann Cells cover each axon in the PNS.

• Each Oligodendrocyte covers parts of multiple axons in the CNS.

• Astrocytes

– most abundant glial cells - form framework of CNS – form an important part of the “blood-brain barrier” by

separating neurons from capillaries

– help regulate the composition of brain tissue intercellular fluid – can produce action potentials like neurons

• Ependymal Cells form a ciliated simple columnar epithelium that lines cavities in the CNS and circulate cerebrospinal fluid (CSF).

• Microglia are bone marrow derived macrophages that move into the CNS and concentrate in areas of infection, trauma or stroke.

http://www.smartshunt.ethz.ch/project/FormerProject/ventricles_color?hires

Myelin Sheath

• Myelin is formed by multiple wrappings of a glial cell

membrane around an axon.

– Myelin is formed by oligodendrocytes in the CNS and by Schwann cells in the PNS.

– Myelination takes place during development of the nervous system.

– Wrappings of glial cell plasma membrane are about 20% protein and 80% lipid and make the axons look shiny white. – Not all axons are myelinated, but all axons are covered by

glial cells.

– Schwann cells hold short unmyelinated axons in grooves with only one membrane wrapping.

• Gaps between myelin segments are called

Nodes of Ranvier

– these “gaps” are extremely small spaces where two myelin segments meet.

Myelin Sheath Formation

Unmyelinated Axon

Myelin Sheath

Axons

Node of Ranvier

Schwann Cell

Electrical Potentials and Currents

• Nerve pathways are not continuous “wires” but a

series of separate cells that relay signals.

• Neuronal communication is based on mechanisms for

producing electrical potentials and currents.

– electrical potential - difference in concentration of charged ions across a membrane measured in millivolts (mV)

– electrical current - flow of ions across a membrane measured in milliamps (mA)

• Living cells have polarized membranes.

– Ions are maintained by the cell at different concentrations inside and outside of the cells.

– Membrane polarity of a resting (inactive) neuron is about

-_{70 mV because of a relatively negative charge inside of the}

Electrical potentials of living cells are measured using a sensitive voltmeter with tiny glass electrodes.

One electrode is placed inside the cell (intracellular) and one electrode is placed just outside the cell (extracellular).

note: a sheet of paper is about 100 m thick!

Neurophysiologists make extremely thin glass recording electrodes from glass tubes with instruments that precisely control the heat and tension on the tube. These hollow glass needles are then filled with a conducting salt solution.

Resting Membrane Potential (RMP)

• RMP is a voltage difference across the membrane

of an inactive neuron and is usually about -70 mV.

• RMP is caused by:

– unequal ion distribution between Extracellular Fluid (ECF) and the Intracellular Fluid (ICF) caused by

selective permeability of plasma membrane and active transport.

– Na+_/K+ _{pumps transport Na}+ _{and K}+ _{in a 3:2 ratio}

3 Na+ _{out of the neuron and 2 K}+ _{into the neuron}

• pumps work continuously and require ATP

• high use of ATP means glucose and oxygen must be supplied continuously to nerve tissue

– large cytoplasmic anions do not escape (anionic proteins, PO₄2-_{, SO}

Local Potentials

• Dendrite and soma membranes start to depolarize in

a particular location when a neuron is stimulated by

ligands (hormones or neurotransmitters from another

cell), light, heat or a mechanical disturbance.

– membrane depolarizes due to opening of gated

Na

+

_{channels that let Na}

+

_{rush in according to its}

concentration and electrical gradients

• Local Potentials:

– are graded (vary in magnitude with stimulus

strength)

– are decremental (get weaker the farther they

spread)

– are reversible (as K

+

_{leaks out of cell and the}

Na

+

_/K

+

_{pump works to restore membrane polarity)}

Generation

of a Local

Membrane

Summation of Depolarizations from Local Potentials

can lead to an Action Potential

Local depolarizing

potentials are excitatory. Local potentials that bring the cell closer to

threshold are called EPSPs (excitatory

postsynaptic potentials). Depolarization must

reach a threshold to

trigger an action potential Local hyperpolarizing

potentials would be inhibitory.

Postsynaptic Potentials

• Excitatory postsynaptic potentials (EPSP) cause a positive voltage change in the postsynaptic cell making it more likely to fire (depolarize).

– result from Na+ _{flowing into the cell}

– noradrenaline and glutamate are excitatory neurotransmitters

• Inhibitory postsynaptic potentials (IPSP) cause a voltage

change in the postsynaptic cell that makes it less likely to fire because it is hyperpolarized.

– results from Cl- _{flowing into the cell or K}+ _{leaving the cell}

– glycine and GABA (gamma aminobutyric acid) are examples of inhibitory neurotransmitters

• Some neurotransmitters, like ACh and norepinephrine, can be either excitatory or inhibitory depending on the type of

Excitatory (a)

and Inhibitory (b)

Postsynaptic

Potentials

Summation of Postsynaptic Potentials

• Temporal Summation occurs when a single cell receives many EPSPs in a short period of time. • Spatial Summation

occurs when a single cell receives many EPSPs from more than one presynaptic cell.

Summation of IPSP’s Inhibit Neurons

• Inhibitory Neuron “I” suppresses presynaptic neuron “S” by releasing an inhibitory neurotransmitter like glycine.

• Inhibitory neurotransmitters can block voltage-gated calcium channels and open K+ channels in neuron “S” dropping its

membrane potential so it will not release neurotransmitter onto neuron “R” .

Action Potential

• Action Potential plotted on

a realistic timescale looks

like a “spike”.

• Initial depolarization events

are very subtle and happen

very quickly.

• Characteristics of an AP

– follows an all-or-none law • voltage gates either open

or they don’t

– irreversible (once started, it goes to completion and can not be stopped)

Action Potential at the Axon Hillock

1. Sodium influx due to local potential spreads to the high density of voltage-gated

channels at the trigger zone (500 channels/m2 at hillock vs 50 channels/m2 on soma).

2. If threshold potential (-55mV) is reached, voltage-gated Na+

channels open (more Na+ _enters

causing more depolarization). 3. Voltage-gated Na+ channels

open quickly. Incoming Na+

further depolarizes membrane which opens more Na+ _channels

(positive feedback). Voltage gated K+ _{channels slowly start to}

open.

4. Na+ _{channels are inactivated}

and close above 0mV.

Membrane is now positive on the inside.

5. Voltage-gated K+ channels fully open, K+ _{diffuses out. K} + _outflow

and the Na+_/K+ _{pump repolarize}

the membrane.

6. K+ _{channels stay open longer}

than Na+ channels so more K+ leaves the cell and the

membrane voltage

hyperpolarizes below the

resting potential.

7. Ion diffusion through K+ _leak

channels in the membrane or

astrocyte scavenging of K+

from the interstitial fluid restores resting membrane potential.

1 2 3 4 5 1

Phases of the Action Potential

TIME (msec)

Phases of the Action Potential

Time (milliseconds) Memb ran e Po ten tial (mV) Phase 1 2 3 4 5

Name of Phase Resting Membrane

Graded Local

Potential Depolarization Repolarization

Hyper- polarization Na+_/K+ _pump Na+ out K+ _in Na+ _out K+ _in Na+ _out K+ _in Na+ _out K+ _in Na+ _out K+ _in

K+ _{leak channels K}+ _{out K}+ _{out K}+ _{out K}+ _{out K}+ _out

voltage-gated Na+ _channel Closed and ready

to open

Closed and ready

to open Open

Closed and not able to open

Closed and ready to open voltage-gated K+ _{channel Closed Closed Slowly opening Open Slowly Closing}

Ion primarily responsible for the

membrane voltage K

+ _{(out) Na}+ _{(in) Na}+ _{(in) K}+ _{(out) K}+ _(out)

membrane channel(s) primarily responsible for membrane voltage

Na+_/K+ _pump K+ _{leak channels} ligand-gated Na+ channels voltage-gated Na+ channels voltage-gated K+ channels voltage-gated K+ _channels Na+_/K+ _pump

Depol ariz ati on Repolariz ation Hy per polariz ation Memb ran e Po ten tial (mV) Time (milliseconds) 0

Saladin Text page 460: “A traveling nerve signal is an electrical current, but it is not the same as a current traveling through a wire. A current in a wire travels millions of meters per second and is

decremental – it gets weaker with distance. A nerve signal is much slower (not more than 2m/sec in unmyelinated fibers), but is

nondecrimental. Even in the longest axons, the last action potential generated at a synaptic knob has the same voltage as the first one generated at the trigger zone. …We can compare the nerve signal to a burning fuse. When a fuse is lit, the heat ignites powder

immediately in front of this point and this repeats itself in a

self-propagating fashion until the end of the fuse is reached. At the end, the fuse burns just as hotly as it did at the beginning. In a fuse the combustible powder is the source of potential energy that keeps the process going in a nondecremental fashion. In an axon, the potential energy comes from the ion gradient across the plasma membrane. Thus, the signal does not grow weaker with distance; it is

http://www.youtube.com/watch?v=3OdALBhR1zU

http://www.youtube.com/watch?v=b-IRI1bA5jw&feature=related

Burning Fuse

Myth Busters outrunning a gunpowder trail 8:37-9:25

The Refractory Period

• The Refractory Period is when a cell is resistant to

stimulation.

• Assures one way conduction of the impulse

because membrane channels are temporarily

deactivated.

• No stimulus can start an action potential during the Absolute Refractory Period because the voltage-gated Na+

channels are closed. • Another action potential

can be started by a stronger than normal stimulus because some voltage-gated Na+

channels are re-activated.

The Refractory Period

During the Refractory Period, voltage-gated Na+ _{channels are}

Impulse Conduction in Unmyelinated Fibers

• All healthy axons are covered by glial cells.

• Unmyelinated Axons are covered by a single

layer of Schwann cell membrane (in the PNS)

or oligodendrocyte membrane (in the CNS).

• Myelinated Axons are wrapped with many

layers of glial cell membrane.

• Threshold voltage in the trigger zone (axon

hillock) starts the impulse down the axon.

• Nerve signal (impulse) is a chain reaction of

sequentially opening voltage-gated Na

+

channels down entire length of axon.

Speed of Nerve Signals

• Signal speed depends on:

– diameter of the axon

• larger diameter = faster signal conduction because of increased membrane surface area for signal conduction

– myelination

• myelinated axons are faster because of saltatory conduction • axons can be fast and thin (saves space) if they are myelinated

• Speeds:

– slow, unmyelinated fibers conduct at 0.5-2 m/sec (1-4 mph)

• slow pain fibers (burning, aching, throbbing pain) from a sprain, sun burn or stubbing a toe take a relatively long time to reach the CNS and last a long time.

– fast, myelinated fibers conduct at 120 m/sec (268 mph)

• fast pain fibers (sharp, pricking pain like stepping on a thorn) are conducted to the CNS quickly to help prevent further injury

• fast signals are also to skeletal muscles or from sensory organs for vision and balance

Saltatory Conduction in Myelinated Fibers

• Voltage-gated channels at Nodes of Ranvier

– fewer than 25 per m2 _{in myelin-covered regions}

– up to 12,000 per m2 _{in nodes of Ranvier}

• Fast Na+ _{diffusion into axon occurs between nodes}

depolarizing the membrane and generating a local

Saltatory Conduction in Myelinated Fiber

• The action potentials jump from node of Ranvier to

node of Ranvier. (Saltator (L) a leaper, dancer)

Clinical Correlation

• Multiple Sclerosis

– Myelin sheaths formed by oligodendrocytes in the

CNS deteriorate and are replaced by scar tissue.

– Deterioration may be caused by an immune

disorder triggered by a virus in genetically

susceptible individuals.

– Nerve conduction is disrupted. Specific symptoms

depend upon the part of the CNS is involved.

– Symptoms can include double vision, blindness,

speech defects, spontaneous muscle cramps,

tremors, numbness.

R. Douglas Fields “Why White Matter Matters” Scientific American, March 2008.

“Few axons are covered with myelin at birth. More are insulated over time from the back of the cerebral cortex to the front. Basic functional areas such as vision (back) are completed before age 4, followed by language and last, self-control (forehead). Myelin is laid down until age 25 or so, one reason teenagers do not have adult

decision- making abilities”

Age 4 Age 8 Age 12 Age 16 Age 20

Synapses Between Neurons

• Neural Synapse: The specialized junction between

the membranes of two neurons.

– 1st neuron is presynaptic neuron – 2nd neuron is postsynaptic neuron

• First neuron affects the second neuron

– The first neuron releases a chemical called a

neurotransmitter that will bind to a specific receptor on the second neuron. There are over 100 known

neurotransmitters

• Synaptic delay = 0.5 milliseconds

– time for the signal to move from the presynaptic cell to the postsynaptic cell

• Synapse may be axodendritic, axosomatic or

axoaxonic

• Number of synapses on postsynaptic cell is variable:

– 8,000 on spinal motor neuron

Neuron Cytoplasm (red) Synapses (green) Nucleus (purple)

Synaptic Cleft Presynaptic Neuron Postsynaptic Neuron Synaptic Vessicles containing Neurotransmitter

Types of Neurotransmitters

There are over 100 different

neurotransmitters, and these are

classified in 4 major categories:

1. Acetylcholine (ACh)

2. Amino Acid Neurotransmitters

GABA, glycine, aspartic acid

3. Biogenic Amines (Monoamines)

– Catecholamines: epinephrine, norepinephrine, dopamine

– Indolamines: serotonin, histamine

Neuropeptides

Neuropeptides:

• are chains of 2-40

amino acids.

• are stored in synaptic

vesicles in the terminal

boutton.

• are powerful even at low

concentrations.

• have long lasting

effects.

• may also function as

hormones if they are

Synaptic Transmission

Two examples of synapses with different

modes of action:

• Excitatory Adrenergic Synapse

• Inhibitory GABA-ergic Synapse

Excitatory Adrenergic Synapse

• Action potential opens voltage-gated Ca

++

_channels

on presynaptic neuron.

• Ca

++

_{influx triggers release of Norepinephrine (NE)}

into the synapse.

• NE works through a Second Messenger System.

– NE binds to receptors on the postsynaptic cell that starts a chemical cascade resulting in production of a second

messenger, cAMP that can have multiple effects including activating enzymes, activating genes, and activating

ligand-gated ion channels.

• NE is taken back up by the presynaptic neuron and

recycled.

Inhibitory GABA-ergic Synapse

• Pre-synaptic neuron releases GABA

(



-aminobutyric acid) into the synapse.

• GABA binds to receptors on the postsynaptic

cell and triggers the opening of Cl

-

channels

producing a hyperpolarization of the

postsynaptic cell.

• Postsynaptic neuron is inhibited because it is

now further away from threshold.