Lecture 7 Overview of the Nervous System & Neurotransmission

Assoc. Prof Peter Shortland School of Science & Health

p.shortland@uws.edu.au

Learning Objectives

1. 2. 3. 4.

Describe the basic organization of the peripheral and central nervous system Describe the roles of neurons & glial cells in the nervous system Describe how neurons & glia communicate with each other 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 coordinate 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 Sensory the external environment (input) 2. information for assessment Integrate & meaning (processing) 3. a Motor response (behaviour, Effect output) 4. Regulate body homeostasis for optimal performance

Components of the nervous system

1. CNS

2. PNS

Conveys information to & from brain via peripheral nerves

3. ANS
Integrates information from PNS Response, thinking, remembering, reacting

R&D Rest and digest

4 Fs

Controls GI

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

Meninges removed

Both are protected by bone Surrounded by meninges Bathed in fluid Connect to PNS via cranial and spinal nerves

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 (
Have axons

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
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 retina & spinal cord e.g. motoneurons, cortex

Special sense neurons e.g. retina, inner ear, & olfactory 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 pseudounipolar; the axon from the cell body bifurcates into 2 branches
Commonest pseudo-unipolar cells are sensory afferents of the PNS Typical textbook
(Postganglionic motoneurons are also pseudo-unipolar)

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. 2. 3. 4. Astrocytes Microglia Oligodendrocytes Ependymal cells

PNS
1. Schwann cells 2. Satellite cells

Function: Neuronal support and homeostasis

(Glia outnumber neurons by 25:1)

1. Astrocytes
Star-shaped cell that provide Structural and nutrient support to neurons; most numerous cell type in CNS role (regulate Homeostatic 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

Microglia
Resident macrophages Normally, quiescent but have a Surveillance (defence) 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

Oligodendrocytes
axon myelination 1 to many (up to 50 axons) Only found in CNS white matter
CNS

Form myelin sheath by wrapping their myelin processes around axon; cell body does not wrap around axon Damage produces demyelination & alters axon transmission e.g. MS

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 Structural and nutrient support to neuron (analogous to CNS astrocytes)

Schwann cells

Encircle and cover a PNS axon only Single Each Schwann cell produces part of the myelin sheath Gaps between adjacent Schwann cells are called
Nodes of Ranvier

2 types: Myelinating & Non-myelinating (Also help nerves regenerate when damaged)

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

Myelin Sheath

[
D

Schwann cell nucleus

A = Remack bundle, B = medium-sized myelinated axon, C, thinly-myelinated axon, D thickly-myelinated, E = single unmyelinated axon

Classification of peripheral nerve fibres

Axon Diameter (m) Afferents (sensory; input) A (I) Yes 12-20 Ia (large) Ib A (II) Yes 6-12 (medium) Class/ (group) Myelin Conduction velocity (m/s) Human >72 Function/Type of sensation

Joint receptors Muscle spindle Golgi tendon organ Low threshold mechanoreceptors (Pacinian corpuscles, Ruffini endings, Merkel cells, Meissner corpuscles, hair follicles) Secondary flower-spray endings in muscle Mechanical pain Muscle flexor reflex afferents Autonomic afferents Temperature, muscle and visceral pain

30-72

A (III) C (IV)

Yes, thin No

1-6 (small) <1 (tiny)

5-29 0.5-2

Efferents (motor/output) A Yes 12-20 A 5-8 B Yes, <3 thin C No <1

>72 30-48 3-30

0.5-2

Motor to skeletal muscle fibres Motor to muscle spindle (Ia) fibres

Autonomic preganglionic efferents 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 neurotransmitters into a synaptic cleft

Overview of neurotransmission
4 stages

R M P

Presynaptic cell Main neurotransmitters =

Glutamate (+) GABA/Glycine (-)

Information processing

Postsynaptic cell

Biophysical requirements for action potentials

Excitability
Cells have a
Resting membrane potential

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.
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
High extracellular Na+, Cl-, low K+
High intracellular K+, low Cl-, Na+

Resting membrane potential (~70mV)

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 No transmittion
3 out

2 in

Types of ion channels

Ligand gated Voltage gated

Activation gate

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 to supra maximal stimuli

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 (= Inhibitory ) Depolarization membrane potential becomes more positive; AP possible if depolarization large enough (= 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

Membrane potential (mV)

AP threshold

Stimulus 1

Stimulus 2

Time ms

Temporal summation

Spatial summation

Signal transduction = conversion from stimulus to electrical signal

Generator potential
AP threshold ( -35 to -25 mV) Depolarise ( -55 to -35 mV) Resting potential (-55mV DRG)

PERIPHERAL STIMULUS

Action potential

Presynaptic Excitatory neuron Post synaptic potential

Action potential
neurotransmitter

Action potential Postsynaptic neuron

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
~1m

~1mm

2 major advantages of myelination: Speed & energy efficiency

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)

SUMMARY OF NEUROTRANSMISSION: 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

Pre-synaptic neurons

Transmitters

excitatory;

inhibitory

..
Postsynaptic neuron

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 gliotransmitters 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