Lecture 7

Overview of the Nervous

System & Neurotransmission

Assoc. Prof Peter Shortland

School of Science & Health p.shortland@uws.edu.au

Learning Objectives

1. Describe the basic organization of the peripheral and central nervous system

2. Describe the roles of neurons & glial cells in the nervous system

3. Describe how neurons & glia communicate with each other

4. Describe how an action potential is generated & propagated along axons

What is a nervous system?

Definitions:

The system of cells, tissues, and organs that regulates the

body's responses to internal and external stimuli. In vertebrates

it consists of the brain, spinal cord, nerves, ganglia, and parts of

the receptor and effector organs. The Free Dictionary

The entire integrated system of nerve tissue in the body:

the brain, brainstem, spinal cord, nerves and ganglia. The

sensory and control apparatus consisting of a network of nerve

cells. The system of nerve tissue that allows organisms to co-

ordinate bodily reactions from the CNS and gather information

from the external environment to be processed in the CNS.

Biology Online

What does a nervous system do?

1. Gather information from

the external environment (input)

2. information for assessment

& meaning (processing)

3. a response (behaviour,

output)

4. Regulate body homeostasis for

optimal performance

Sensory

Integrate

Effect Motor

Components of the nervous system

2. PNS Conveys information

to & from brain via peripheral nerves

• Integrates information from PNS

• Response, thinking, remembering, reacting

1. CNS

3. ANS

R&D 4 Fs ControlsGIRest and digest

What is the brain?

Definition:

• an organ of soft nervous tissue contained

in the skull, functioning as the coordinating

centre of sensation and intellectual and

nervous activity (Oxford English Dictionary)

• Centre of the nervous system in

vertebrates (& most invertebrates)

• Made up of neurons, axons and glial cells

• Has 3 main parts (fore- mid- & hind-brain)

The CNS: brain & spinal cord

• Both are protected by bone

• Surrounded by meninges

• Bathed in fluid

• Connect to PNS via cranial and spinal nerves

Meninges

removed

The CNS consists of grey matter

& white matter

• Grey matter contains neuron cell bodies, dendrites

& glial cells (40%)

• White matter is largely myelin that surround nerve

axons (60%) Axons and very few cells

There are 2 main cell types in the

nervous system

1. Neurons ( )

• Main excitable cells that generate and transmit electrical

signals (impulses)

• Function: to carry out most of the unique functions of

the nervous system e.g. thinking, sensing,

remembering, controlling, muscle activity & glandular

secretions

Have axons

I.e. Cellular communication

Basic Neuronal structure:

4 important parts 1. Dendrites are short, branched

and unmyelinated; conduct

impulses (synaptic potentials)

toward cell body

• Contain cell surface receptors

for specific neurotransmitters

2. Cell body & dendrites

receive contacts (synapses)

from other cells

hillock

Neuronal structure continued

3. Axon (“nerve fibre”)

• cable – long thin &

cylindrical

• can be unmyelinated &

myelinated

• conducts electrical

impulses to axon terminal

• Length – few um to >1m

4. Axon terminal contains

synaptic end bulbs that

release neurotransmitters

in response to electrical

impulses

CNS neuronal cell types:

morphological variation

Most neurons of brain Special sense neurons e.g.

retina & spinal cord e.g. retina, inner ear, & olfactory

motoneurons, cortex system or CNS interneurons

PNS Neuronal cell types

Strictly speaking: unipolar neurons

have 1 axon only conducting from

dendrite to terminal. Commonly

found in invertebrates e.g. insects

but NOT in humans.

Actually this neuron is pseudo-

unipolar; the axon from the cell

body bifurcates into 2 branches

Commonest pseudo-unipolar

cells are sensory afferents of the

PNS (Postganglionic motoneurons are also

pseudo-unipolar) Typical “textbook”

Example of a PNS neuronal cell:

skin peripheral receptor

• Distal axon terminal often a specialised ending e.g.

pacinian corpuscle

• Action potential propagates from distal to proximal

end

The other main cell type in

nervous tissue is Glia

2. Glia (no axons)

CNS

1. Astrocytes

2. Microglia

3. Oligodendrocytes

4. Ependymal cells

PNS

1. Schwann cells

2. Satellite cells

(Glia outnumber neurons by 25:1)

Function:

Neuronal support and homeostasis

1. Astrocytes

• Star-shaped cell that provide

to neurons; most

numerous cell type in CNS

• role (regulate

tissue pH, mop up & metabolise excess

neurotransmitters)

• Control movement of (potentially

harmful) substances from blood into

brain (main role) by forming the blood

brain barrier by covering blood

capillaries with their many end feet

• Form scar tissue when CNS is

damaged; prevents regeneration

Structural and nutrient support

Homeostatic

Microglia

• Resident macrophages

• Normally, quiescent but have a

role

• 1st part of active immune

defense against infection,

disease or trauma

• Become mobile & phagocytic -

eat cellular debris; rapidly

multiply & change shape

• Can be found in grey & white

matter

Surveillance (defence)

Oligodendrocytes

• axon myelination

– 1 to many (up to 50 axons)

• Only found in white matter

• Form myelin sheath by

wrapping their myelin

processes around axon; cell

body does not wrap around

axon

• Damage produces de-

myelination & alters axon

transmission e.g. MS

CNS

CNS

Ependymal cells

• Line cerebral cavities (ventricles) and

central canal in the spinal cord that

contain cerebrospinal fluid (CSF)

• Single layer of cuboidal/columnar ciliated

cells that aid in circulating CSF

Summary of the arrangement of glial

cells in the CNS

Glial cells in the PNS

• Surround neuronal cell bodies in peripheral

sensory & autonomic ganglia

• Flattened cells that provide

support to neuron (analogous to CNS astrocytes)

Structural and nutrient

Schwann cells

• Encircle and cover a PNS axon only

• Each Schwann cell produces part of the myelin

sheath

• Gaps between adjacent Schwann cells are called

• 2 types: Myelinating & Non-myelinating

• (Also help nerves regenerate when damaged)

Single

Nodes of Ranvier

Myelinating Schwann cells • Form a myelin sheath by wrapping

many layers of lipid rich cell

membrane around axon; cytoplasm

squeezed to periphery

• Myelin sheath acts as an electrical

insulator; speeds up conduction of

nerve impulses

• Conduction velocity is proportional

to myelin thickness (i.e. they are

FAST)

• Found around axons of motor &

sensory neurons

• Histologically, myelinated nerve fibres

appear white

Non-myelinating Schwann cells

• One Schwann cell can

wrap around several

fibres to form a

REMACK bundle

• These are all small

diameter fibres &

therefore have SLOW

conduction velocities

• Histologically, the nerve

fibres appear grey

Electron microscopic view of a nerve

D

A = Remack bundle, B = medium-sized myelinated axon, C,

thinly-myelinated axon, D thickly-myelinated, E = single

unmyelinated axon

E Myelin

Sheath

Schwann

cell

nucleus

[

Classification of peripheral nerve fibres

Class/

(group)

Myelin Axon

Diameter

(m)

Conduction

velocity (m/s)

Human

Function/Type of sensation

Afferents (sensory; input)

A (I)

Ia

Ib

Yes 12-20

(large)

>72 Joint receptors

Muscle spindle

Golgi tendon organ

A (II)

Yes 6-12

(medium)

30-72

Low threshold mechanoreceptors

(Pacinian corpuscles, Ruffini endings,

Merkel cells, Meissner corpuscles, hair

follicles)

Secondary “flower-spray” endings in

muscle

A (III)

Yes,

thin

1-6

(small)

5-29

Mechanical pain

Muscle flexor reflex afferents

Autonomic afferents

C (IV)

No <1

(tiny)

0.5-2 Temperature, muscle and visceral pain

Efferents (motor/output)

A

A

Yes 12-20

5-8

>72

30-48

Motor to skeletal muscle fibres

Motor to muscle spindle (Ia) fibres

B Yes,

thin

<3 3-30 Autonomic preganglionic efferents

C No <1 0.5-2 Autonomic postganglionic efferents

How do neurons communicate with

each other?

Neurotransmission

• Neurons receive signals (electrical or chemical) and

transmit them to other cells

• These graded synaptic potentials produce ipsps

or epsps which are added together over time &

space (temporal and spatial summation).

• If their total exceeds a threshold value the trigger

zone fires an electrical impulse called an Action

Potential

• It is of fixed size & propagates unchanged along the

axon to the synapse to cause release of neuro-

transmitters into a synaptic cleft

Overview of neurotransmission

Information

processing Pre-

synaptic

cell

Post-

synaptic

cell

R

M

P

Main neurotransmitters =

4 stages

Glutamate (+)GABA/Glycine (-)

Biophysical requirements for

action potentials

Excitability

• Cells have a due to

– differences in concentration of ions inside vs outside of cell

– differences in membrane permeability for different ions

• is the capacity to change this

membrane potential

• Essential property of neurons: gives rise to the

action potential

• Also found in a range of excitable cells typically

muscle cells e. g. skeletal muscle, cardiac muscle.

Resting membrane potential

Excitability

The biophysical requirements for the

resting membrane potential (RMP)

• Ion gradient across cell membranes – Difference in [ions] inside vs outside

creates a chemical gradient

Resting membrane potential

(~70mV)

High extra-

cellular Na+, Cl-,

low K+

High intra-

cellular K+,

low Cl-, Na+

Cell membrane is a lipid bilayer + proteins

• Normally cell membrane is impermeable to ions

• Charged ions only move through integral membrane

proteins called channels

• Process = facilitated diffusion

Types of Ion channels

1. “Leak” channels responsible for resting

membrane potential (channel open all the time)

2. Ligand gated – open in response to chemical

stimuli acting on their receptors found on

channels e.g. peripheral sensory receptors

3. Voltage gated – open in response to changes in

membrane potential

4. Stimulus transducing (mechanical,

temperature, acidity)- open as a result of

physical stimulus

• Action potential driven by voltage gated

sodium and potassium channels

“Leak” channels contribute to the

resting membrane potential

• Due to concentration gradients

across the membrane Na+ & K+ ions

leak across the membrane

• There are more K+ than Na+

channels in the membrane so more

K+ leaks out creating an increased

negative charge inside the cytosol =

membrane potential

• Membrane potential changes when

permeability to ions change

• Changes in RMP are signals used

to receive integrate & send

information

Active ion pumps:

The Na+/K+ ATPase exchanger • Requires energy to transport ions against concentration

gradient; Contributes to development of resting membrane

potential

• Without it eventually Na+ influx through leak channels would

destroy the RMP resulting in

3 out

2 in

No transmittion

Types of ion channels

Activation gate

Voltage gatedLigand gated

Voltage gated ion channels have

activation & inactivation gates Using Na+ as an example:

• At rest activation gate is

closed (inactivation is open)

• When voltage changes

during depolarization, the

activation gate opens (Na+

rushes in)

• Inactivation gates block

pore during repolarization

phase;

• During hyperpolarization

phase both gates reset

The action potential

• A series of 4 rapidly occurring events that

change & then restore the membrane

potential of a cell to its resting state

• Involves Na+ & K+ channels

Stage 1 of the action potential:

Resting state

• In the resting state, ion

channels are closed

• Resting membrane held

at ~ -70mV

• Stimulus causes

generator potentials

(usually excitatory) which

depolarise cell to the

threshold potential

Stage 2 of the action potential:

Depolarisation phase

• Na+ channels are open

• Na+ enters down

concentration gradient

rapidly depolarising the

cell and changing voltage

• Note: K+ channels are

opening very slowly

• They are fully open by

end of this phase

Stage 3 of the action potential:

Repolarization phase

• At peak Na+ gates shut

(inactivated) so no

more depolarization

can occur even if more

stimuli occur

• K+ channels fully open

to expel +ve charge

along concentration

gradient causing

repolarization

Stage 4 of the action potential:

Return to the resting state

• K+ channels slowly

closing

• Membrane becomes

more negative as K+

approach equilibrium

producing the after

hyperpolarisation

• The RMP is regained by

K+ ions leaving via leak

channels

• Na+ gates resetting

Refractory periods (Na+ channels inactivated) (prior to closure of K+ channels)

No new APs possible

APs possible tosupra maximalstimuli

Action potential threshold: “all-or-none”

AP size same independent of stimulus

Frequency encoding of information by action

potentials is proportional to stimulus intensity

Generator (graded) potentials

• A change in the RMP can occur

in 2 ways: graded & action

potentials (AP)

• Graded potentials involve small

local deviations from the RMP

– Hyperpolarization – membrane

potential becomes more negative;

No AP possible (= )

– Depolarization – membrane

potential becomes more positive;

AP possible if depolarization large

enough (= )

Inhibitory

Excitatory

Graded potentials

• Graded potentials arise

due to movement of ions

through stimulus-gated &

ligand-gated ion channels

• Short distance & short

lived

• Size varies with stimulus

strength (larger=stronger)

• Can summate

• May produce an action

potential Stimulus 1 Stimulus 2

Time ms

Mem

bra

ne p

ote

nti

al

(mV

)

AP threshold

Temporal summation

Spatial summation

Action potential Action potential

Action potential

Generator potential

Resting potential

(-55mV DRG)

Depolarise

( -55 to -35 mV)

AP threshold

( -35 to -25 mV)

PERIPHERAL

STIMULUS

Excitatory Post synaptic potential

neurotransmitter

Presynaptic

neuron

Postsynaptic neuron

Signal transduction =

conversion from stimulus to electrical signal

AP propagation in

unmyelinated axons • Passive

• Ionic current flows across each adjacent

segment of the membrane

• Step by step depolarization & repolarization of

each voltage gated ion channel in membrane

• Slow

AP propagation in myelinated

axons: saltatory conduction • Propagation of AP from one node of Ranvier to next

• AP at 1st node generates ionic currents in cytosol &

interstitial fluid that open ion channels at next node

• AP "jumps" along axon, skipping myelin region

• Increases conduction velocity of action potentials

and their energy efficiency

~1µm

~1mm

Since ionic currents are confined to nodes of

Ranvier, fewer ions ‘leak’ across the membrane

> saves metabolic energy > selective advantage

(human nervous system uses ~20% of body's

metabolic energy)

Myelinated segments long enough for signals to

travel for at least two nodes while retaining enough

amplitude to fire an AP at 2nd or 3rd node

high safety factor of saltatory conduction, (allows

transmission to bypass nodes in case of injury)

2 major advantages of myelination:

Speed & energy efficiency

… …

Transmitters

… excitatory; … inhibitory

SUMMARY OF NEURO-

TRANSMISSION: If the

sum of all excitatory &

inhibitory post synaptic

potentials is a

depolarisation that

reaches threshold then

an action potential is

generated at the axon

hillock of the post

synaptic neuron

Postsynaptic neuron

…..

Pre-synaptic neurons

How do glial communicate?

Gliotransmission • Glia do not have axons

• Glia communicate by using

electrical synapses (GAP

junctions on end feet; highly

secure; synchronised)

• Glia communicate with each

other and with neurons via

tripartite synapses

• Glia also release “glio-

transmitters” e.g. Glutamate

& ATP that act on receptors

on neurons and other glia

The tripartite synapse: Presynaptic NT

release activate astrocyte receptors

elevating Ca levels causing release of

other neurotransmitters that modulate

pre/post synaptic neuronal function

Key three points

Self-Test Question 1

Which glial cell acts as a “butler” to

neurons by providing structural & nutrient

support?

A. Astrocyte

B. Ependymal cell

C. Microglial cell

D. Oligodendrocyte

E. Schwann cell

Self test question 2

During the depolarisation phase of an action

potential which of the following is true?

A. Both potassium and sodium channels are open

B. Both potassium and sodium channels are closed

C. Potassium channels open slowly and sodium

channels close

D. Potassium channels are closed and sodium

channels are open

E. Potassium channels open slowly and sodium

channels are open

Self test question 3

Saltatory conduction occurs in

A. Dendrites

B. Glial cells

C. Myelinated axons

D. Synaptic junction

E. Unmyelinated axons