Nervous System Overview 🧠

After studying this chapter, you should be able to:

 12.1 describe the structures and basic functions of the nervous

system

 12.2 compare the structures and functions of neurons and neuroglia,

and white matter and grey matter

 12.3 describe the types of electrical signals that permit

communication among neurons

 12.4 describe signal transmission at a chemical synapse,

summation, and excitatory and inhibitory neurotransmitters

 12.5 describe the classes and functions of neurotransmitters

 12.6 identify the various types of neural circuits in the nervous

system

 12.7 explain neurogenesis and the events involved in damage and

repair of peripheral nerves.

Nervous Tissue and Homeostasis

The excitable characteristic of nervous tissue allows for the generation

of nerve impulses (action potentials) that provide communication with
and regulation of most body organs.

Organization of the Nervous System 🌐

The nervous system is a complex network of billions of neurons and even

more neuroglia, organized into two main subdivisions:

1. Central Nervous System (CNS)

2. Peripheral Nervous System (PNS)

The nervous system carries out a complex array of tasks. It allows us to

sense various smells, produce speech, and remember past events; in
addition, it provides signals that control body movements and regulate the
operation of internal organs. These diverse activities can be grouped into
three basic functions: sensory (input), integrative (process), and motor
(output).

Central Nervous System (CNS) 🧠

The CNS consists of the brain and spinal cord.

 Brain: Located in the skull and contains about 85 billion neurons.

  Spinal Cord: Connected to the brain through the foramen magnum
and encircled by the vertebral column; contains about 100 million
neurons.

The CNS processes incoming sensory information and is the source of

thoughts, emotions, and memories. It also generates signals that
stimulate muscles and glands.

Peripheral Nervous System (PNS) 📡

The PNS consists of all nervous tissue outside the CNS. Components
include:

 Nerves: Bundles of axons plus associated connective tissue and

blood vessels.

 Ganglia: Small masses of nervous tissue containing neuron cell

bodies, located outside the brain and spinal cord.

 Enteric Plexuses: Networks of neurons in the walls of

gastrointestinal tract organs.

 Sensory Receptors: Structures that monitor changes in the

external or internal environment.

The PNS is divided into:

1. Somatic Nervous System (SNS)

2. Autonomic Nervous System (ANS)

3. Enteric Nervous System (ENS)

Somatic Nervous System (SNS) 💪

The SNS consists of:

1. Sensory neurons: Convey information to the CNS from somatic

receptors in the head, body wall, and limbs, and from receptors for
the special senses.

2. Motor neurons: Conduct impulses from the CNS to skeletal

muscles only.

The action of the SNS is voluntary.

Autonomic Nervous System (ANS) ⚙️

The ANS consists of:

1. Sensory neurons: Convey information to the CNS from autonomic

sensory receptors, located primarily in visceral organs.
 2. Motor neurons: Conduct nerve impulses from the CNS to smooth
muscle, cardiac muscle, and glands.

The action of the ANS is involuntary. It has two branches:

 Sympathetic Division: Supports exercise or emergency actions

('fight-or-flight').

 Parasympathetic Division: Takes care of 'rest-and-

digest' activities.

Enteric Nervous System (ENS) Gut Brain 🧠

The ENS, or 'brain of the gut', is involuntary. It consists of over 100

million neurons in enteric plexuses that extend most of the length of the
gastrointestinal tract.

 Sensory neurons: Monitor chemical changes and stretching of the

GI tract walls.

 Motor neurons: Govern contractions of GI tract smooth muscle,

secretions of GI tract organs, and activities of GI tract endocrine
cells.

Functions of the Nervous System 🎯

The nervous system has three basic functions:

1. Sensory (Input): Detecting internal and external stimuli.

2. Integrative (Process): Analyzing sensory information and making

decisions for appropriate responses.

3. Motor (Output): Activating effectors (muscles and glands) to

respond.

For example, when you answer your cell phone:

 The sound stimulates sensory receptors in your ears.

 This auditory information is processed in the brain, and the decision

to answer is made (integrative function).

 The brain stimulates muscles to grab the phone and press the
appropriate button (motor function).

Here we see a diagram of the nervous system, specifically detailing the

CNS and PNS. The CNS includes the brain and spinal cord, while the PNS
includes the nerves, ganglia, enteric plexuses, and sensory receptors.
Here we see a flowchart illustrating the Central Nervous System (CNS) and
its connections to the Peripheral Nervous System (PNS). The CNS includes
the brain and spinal cord, while the PNS includes the Autonomic Nervous
System (ANS), Somatic Nervous System (SNS), and Enteric Nervous
System (ENS).

Clinical Connection: Regulating Your Temperature

The body maintains a constant core temperature through physiological

adjustments controlled by the hypothalamus. This involves feedback
from neurons sensitive to changes in skin and blood temperature. The
hypothalamus maintains the set point for body temperature through
reflexes that cause vasodilation and sweating when the body is too warm,
or vasoconstriction and shivering when the body is too cold.

Histology of Nervous Tissue 🔬

Nervous tissue comprises two types of cells:

 Neurons

 Neuroglia

Neurons are specialized cells that provide unique functions of the

nervous system, such as sensing, thinking, remembering, controlling
muscle activity, and regulating glandular secretions.

Neuroglia support, nourish, and protect neurons, and maintain the

interstitial fluid that bathes them.

Neurons (Nerve Cells) 🧠

Neurons possess electrical excitability – the ability to respond to a

stimulus and convert it into an action potential.

Electrical excitability: The ability to respond to a stimulus and convert it

into an action potential.

A nerve impulse (action potential) begins and travels due to the

movement of ions (such as sodium and potassium) between interstitial
fluid and the inside of a neuron through specific ion channels in its plasma
membrane.

Most neurons have three parts:

1. Cell Body

2. Dendrites
 3. Axon

 Cell Body (Soma): Contains typical cellular organelles. Also

contains Nissl bodies (clusters of rough endoplasmic reticulum) for
protein synthesis. The cytoskeleton
includes neurofibrils (intermediate filaments for cell shape and
support) and microtubules (for moving materials). Ageing neurons
contain lipofuscin (a pigment that accumulates but doesn't harm
the neuron).

 Dendrites: Receiving or input portions of a neuron. They contain

numerous receptor sites for binding chemical messengers from
other cells.

 Axon: Propagates nerve impulses towards another neuron, muscle

fibre, or gland cell. It joins the cell body at the axon hillock. Nerve
impulses arise at the trigger zone (junction of the axon hillock and
initial segment). The cytoplasm of an axon is called axoplasm,
surrounded by the axolemma. Side branches called axon
collaterals may branch off.

The site of communication between two neurons or between a neuron and

an effector cell is called a synapse. Axon terminals swell into synaptic
end bulbs or exhibit varicosities, which contain synaptic vesicles that
store a neurotransmitter.

Neurotransmitter: A molecule released from a synaptic vesicle that

excites or inhibits another neuron, muscle fibre, or gland cell.

Many neurons contain two or even three types of neurotransmitters, each

with different effects on the postsynaptic cell.

Axonal Transport 🚚

Axonal transport is a cellular process responsible for the movement of

organelles, proteins, and other essential materials between the cell body
(soma) and the axon terminals in neurons.

There are two main types of axonal transport:

1. Slow Axonal Transport: Moves materials about 1–5 mm per day

and conveys axoplasm from the cell body towards the axon
terminals.

2. Fast Axonal Transport: Moves materials at 200–400 mm per day

using proteins as 'motors' along microtubules. It moves materials in
both directions:
  Anterograde (forward) direction: Moves organelles and
synaptic vesicles from the cell body to the axon terminals.

 Retrograde (backward) direction: Moves membrane

vesicles and other cellular materials from the axon terminals
to the cell body to be degraded or recycled.

Here we see a diagram of a multipolar neuron showcasing its structure

and various components, like the cell body, dendrites, axon, synapse, and
neurotransmitters.

Structural Diversity in Neurons 📏

Neurons vary greatly in size and shape. Cell bodies range from 5
micrometres (μm) to 135 μm in diameter. The pattern of dendritic
branching varies. Some neurons lack an axon, and others have very short
axons. The longest axons extend from the toes to the brain.

Classification of Neurons 📚

Neurons are classified structurally and functionally.

Structural Classification

Neurons are classified according to the number of processes extending

from the cell body:

1. Multipolar Neurons: Several dendrites and one axon. Most

neurons in the brain and spinal cord are of this type, as well as all
motor neurons.

2. Bipolar Neurons: One main dendrite and one axon. Found in the
retina of the eye, the inner ear, and the olfactory area of the brain.

3. Unipolar Neurons: Dendrites and one axon that are fused together
to form a continuous process. More appropriately
called pseudounipolar neurons. The dendrites function as
sensory receptors.

Here we see a diagram that illustrates the structural classification of

neurons, showcasing their components. The image features three types of
neurons: multipolar, bipolar, and unipolar, each labeled with its
corresponding type.

Functional Classification
Neurons are classified according to the direction in which the nerve
impulse is conveyed with respect to the CNS:

1. Sensory (Afferent) Neurons: Contain sensory receptors at their

distal ends or are located just after sensory receptors. They convey
action potentials into the CNS. Most are unipolar.

2. Motor (Efferent) Neurons: Convey action potentials away from

the CNS to effectors (muscles and glands) in the periphery. Motor
neurons are multipolar in structure.

3. Interneurons (Association Neurons): Located within the CNS

between sensory and motor neurons. They integrate incoming
sensory information and elicit a motor response. Most are
multipolar.

Neuroglia (Glia) 🧠

Neuroglia make up about half the volume of the CNS. They support and
protect neurons, and unlike neurons, they can multiply and divide in the
mature nervous system. There are six types of neuroglia:

 CNS: Astrocytes, oligodendrocytes, microglia, and ependymal cells.

 PNS: Schwann cells and satellite cells.

Resting Membrane Potential ⚡

The resting membrane potential is determined by three major factors:

1. Unequal distribution of ions in the ECF and cytosol.

2. Inability of most anions to leave the cell.

3. The electrogenic nature of the Na+–K+Na+–K+ ATPases.

Graded Potentials ⚡

Graded potentials are small deviations from the resting membrane

potential. These deviations can either make the membrane more
polarized (inside more negative) or less polarized (inside less negative).

 If the response makes the membrane more polarized, it is termed

a hyperpolarizing graded potential.

 If the response makes the membrane less polarized, it is termed

a depolarizing graded potential.

Graded potentials occur when a stimulus causes mechanically gated or

ligand-gated channels to open or close in an excitable cell's plasma
membrane. These potentials are mainly found in the dendrites and cell
body of a neuron.
The amplitude (size) of a graded potential varies depending on the
strength of the stimulus. This means they are larger or smaller depending
on how many ion channels open or close and how long they stay open.

Graded potentials produce a flow of current that is localized, spreading to

adjacent regions along the plasma membrane for a short distance before
gradually dying out. This is known as decremental conduction. Due to
their short range, graded potentials are only useful for short-distance
communication.

The image above illustrates graded potentials. Most graded potentials

occur in the dendrites and cell body. During a hyperpolarizing graded
potential, the membrane potential is inside more negative than the
resting level. Conversely, during a depolarizing graded potential, the
membrane potential is inside less negative than the resting level.

Summation of Graded Potentials ➕

An individual graded potential can become stronger and last longer

through summation, where graded potentials add together.

 Two depolarizing graded potentials summate to produce a larger

depolarizing graded potential.

 Two hyperpolarizing graded potentials summate to produce a larger

hyperpolarizing graded potential.

 If equal but opposite graded potentials summate, they cancel each

other out.

Graded potentials have different names based on the stimulus causing

them and where they occur. For example:

 In response to a neurotransmitter, a graded potential is called

a postsynaptic potential.

 In sensory receptors and sensory neurons, they are

termed receptor potentials and generator potentials.

The image above shows a graded potential forming in response to the

opening of mechanically gated channels or ligand-gated channels. In (a), a
mechanical stimulus (pressure) opens a mechanically gated channel that
allows passage of cations into the cell, causing a depolarizing graded
potential. In (b), the neurotransmitter acetylcholine opens a cation
channel that allows passage of Na+, K+, and Ca2+; Na+ inflow is greater
than either Ca2+ or K+ outflow, causing a depolarizing graded potential.
In (c), the neurotransmitter glycine opens a Cl− channel that allows
passage of Cl− ions into the cell, causing a hyperpolarizing graded
potential.

Action Potentials (AP) 🚀

An action potential (AP), or impulse, is a sequence of rapidly occurring

events that decrease and reverse the membrane potential, eventually
restoring it to the resting state. It has two main phases:

 Depolarizing phase: The negative membrane potential becomes

less negative, reaches zero, and then becomes positive.

 Repolarizing phase: The membrane potential is restored to the

resting state (approximately -70 mV).

 After-hyperpolarizing phase: The membrane potential

temporarily becomes more negative than the resting level.

Two types of voltage-gated channels open and close during an action

potential, mainly in the axon plasma membrane and axon terminals.

Threshold and the All-or-None Principle 🚦

An action potential occurs in the membrane of the axon when

depolarization reaches a certain level, called the threshold (around -55
mV in many neurons). The generation of an action potential depends on
whether a stimulus can bring the membrane potential to this threshold.

 Subthreshold stimulus: A weak depolarization that cannot bring

the membrane potential to threshold; no action potential occurs.

 Suprathreshold stimulus: A stimulus strong enough to depolarize

the membrane to threshold; several action potentials form.

Once generated, the amplitude of an action potential is always the same

and does not depend on stimulus intensity. Instead, a stronger stimulus
above threshold leads to a greater frequency of action potentials.

The all-or-none principle states that an action potential either occurs

completely or not at all.

Phases of an Action Potential 🌊

1. Depolarizing Phase: When a depolarizing graded potential or

stimulus causes the axon membrane to depolarize to threshold,
voltage-gated Na+Na+ channels open, leading to an influx
 of Na+Na+ that changes the membrane potential from -55 mV to
+30 mV.

 Each voltage-gated Na+Na+ channel has an activation gate

and an inactivation gate.

 In the resting state, the inactivation gate is open, but the

activation gate is closed.

 At threshold, both gates open, and Na+Na+ inflow begins.

 As more channels open, the membrane depolarizes further,

and more Na+Na+ channels open in a positive feedback
mechanism.

2. Repolarizing Phase: After a few ten-thousandths of a second, the

inactivation gates of voltage-gated Na+Na+ channels close. Also,
voltage-gated K+K+ channels open, but more slowly than
the Na+Na+ channels.

 Na+Na+ inflow slows, and K+K+ outflow accelerates.

 The membrane potential changes from +30 mV to -70 mV.

 Repolarization also allows inactivated Na+Na+ channels to

revert to the resting state.

3. After-hyperpolarizing Phase: Outflow of K+K+ may be large

enough to cause an after-hyperpolarizing phase.

 Voltage-gated K+K+ channels remain open, and the

membrane potential becomes more negative (around -90 mV).

 As voltage-gated K+K+ channels close, the membrane

potential returns to the resting level of -70 mV.

Refractory Period ⏳

The refractory period is the time after an action potential begins during
which an excitable cell cannot generate another action potential in
response to a normal threshold stimulus.

 Absolute Refractory Period: Even a very strong stimulus cannot

initiate a second action potential. This coincides
with Na+Na+ channel activation and inactivation.

 Relative Refractory Period: A second action potential can be

initiated, but only by a larger than normal stimulus. This coincides
with voltage-gated K+K+ channels still being open after
inactivated Na+Na+ channels have returned to their resting state.
Large-diameter axons have shorter absolute refractory periods, allowing
for higher impulse frequencies.

Propagation of Action Potentials ⚡

To communicate information, action potentials must travel from the

trigger zone of the axon to the axon terminals. Unlike graded potentials,
action potentials do not die out; they maintain their strength as they
spread along the membrane. This is called propagation, and it depends
on positive feedback.

The image above shows the different phases of an action potential. An

action potential arises at the trigger zone and propagates along the axon
to the axon terminals. It consists of a depolarizing phase, a repolarizing
phase, and an after-hyperpolarizing phase.

Continuous and Saltatory Conduction 🏃‍♀️

There are two types of propagation:

 Continuous Conduction: Step-by-step depolarization and

repolarization of each adjacent segment of the plasma membrane.
Ions flow through voltage-gated channels in each adjacent segment.
This occurs in unmyelinated axons and muscle fibers.

 Saltatory Conduction: Occurs along myelinated axons due to the

uneven distribution of voltage-gated channels. Few channels are
present where the myelin sheath covers the axolemma, but many
are present at the nodes of Ranvier.

 The action potential appears to "leap" from node to node,

hence the name "saltatory."

 This is a more energy-efficient mode of conduction.

Factors Affecting the Speed of Propagation 💨

The speed of propagation is affected by:

1. Amount of Myelination: Action potentials propagate more rapidly

along myelinated axons.

2. Axon Diameter: Larger diameter axons propagate action potentials

faster due to their larger surface areas.

3. Temperature: Axons propagate action potentials at lower speeds

when cooled.
Classification of Nerve Fibers 📚

Axons are classified into three groups based on myelination, diameter,

and propagation speeds:

 A Fibers: Largest diameter (5-20 μm), myelinated, with speeds of

12-130 m/sec. Involved in touch, pressure, joint position, and some
thermal and pain sensations, as well as motor impulses to skeletal
muscles.

 B Fibers: Medium diameter (2-3 μm), myelinated, with speeds up to

15 m/sec. Conduct sensory impulses from the viscera and
autonomic preganglionic neurons.

 C Fibers: Smallest diameter (0.5-1.5 μm), unmyelinated, with

speeds of 0.5-2 m/sec. Involved in pain, touch, pressure, heat, cold,
and autonomic postganglionic neurons.

Fiber Diameter Myelinati Speed

Type (μm) on (m/sec) Function

Touch, pressure, joint position, some

A 5-20 Yes 12-130 thermal/pain, motor to skeletal muscles

Sensory impulses from viscera, autonomic

B 2-3 Yes Up to 15 preganglionic neurons

Pain, touch, pressure, heat, cold, autonomic

C 0.5-1.5 No 0.5-2 postganglionic neurons

Muscle Force and Transition Rates 💪

Intact fast and slow skeletal muscles generate approximately the same
amount of peak force (PoPo) of between 200 and 250 kN/m. However,
the rate of transition from the low- to high-force state
shows Ca2+Ca2+ sensitivity and is seven times higher in fast-
twitch compared to slow-twitch skeletal muscle fibres. This higher rate
of transition provides for a greater rate of movement.

Postsynaptic Potentials 🧠

Excitatory Postsynaptic Potentials (EPSP)

Excitatory postsynaptic potentials (EPSPs) cause depolarization of

the postsynaptic membrane, bringing it closer to the threshold.
  A single EPSP normally doesn't initiate a nerve impulse, but the
postsynaptic cell becomes more excitable.

 The cell is partially depolarized, making it more likely to reach

threshold when the next EPSP occurs.

Inhibitory Postsynaptic Potentials (IPSP)

Inhibitory postsynaptic potentials

(IPSPs) cause hyperpolarization of the postsynaptic membrane,
making it more difficult to generate an action potential.

 During hyperpolarization, the membrane potential becomes more

negative and farther from the threshold.

Neurotransmitter Receptors 🫙

Neurotransmitters released from a presynaptic neuron bind

to neurotransmitter receptors in the plasma membrane of a
postsynaptic cell. Each receptor has one or more neurotransmitter
binding sites for its specific neurotransmitter. When a neurotransmitter
binds to its receptor, an ion channel opens, creating either an EPSP or
IPSP.

Types of Neurotransmitter Receptors

Neurotransmitter receptors are classified as either ionotropic

receptors or metabotropic receptors, based on the relationship
between the neurotransmitter binding site and the ion channel.

Receptor
Type Description

The neurotransmitter binding site and the ion channel are components
Ionotropic of the same protein.

The neurotransmitter binding site and the ion channel are components
Metabotro of different proteins; the receptor is coupled to the ion channel via a G
pic protein.

Ionotropic Receptors

An ionotropic receptor is a type of ligand-gated channel.

 In the absence of the neurotransmitter (ligand), the ion channel is

closed.
  When the correct neurotransmitter binds, the ion channel opens,
and an EPSP or IPSP occurs.

Cation Channels and EPSPs

 Many excitatory neurotransmitters bind to ionotropic receptors

containing cation channels.

 EPSPs result from the opening of these channels, allowing passage

of Na+Na+, K+K+, and Ca2+Ca2+.

 Na+Na+ inflow is greater than Ca2+Ca2+ inflow or K+K+ outflow,

causing depolarization.

Chloride Channels and IPSPs

 Many inhibitory neurotransmitters bind to ionotropic receptors

containing chloride channels.

 IPSPs result from the opening of these channels.

 The inward flow of Cl−Cl− ions causes hyperpolarization.

Metabotropic Receptors

A metabotropic receptor contains a neurotransmitter binding site but

lacks an ion channel. It is coupled to a separate ion channel by a G
protein.

 When a neurotransmitter binds to a metabotropic receptor, the G

protein either directly opens/closes the ion channel or activates
a second messenger, which in turn opens/closes the ion channel.

 Some inhibitory neurotransmitters bind to metabotropic receptors

linked to K+K+ channels.

 IPSPs result from the opening of K+K+ channels.

 The outward flow of K+K+ ions causes hyperpolarization.

Same Neurotransmitter, Different Effects 🎭

The same neurotransmitter can be excitatory at some synapses and

inhibitory at others, depending on the structure of the neurotransmitter
receptor to which it binds.

 Example: Acetylcholine (ACh)

 At excitatory synapses, ACh binds to ionotropic receptors with

cation channels, generating EPSPs.
  At inhibitory synapses, ACh binds to metabotropic receptors
coupled to G proteins that open K+K+ channels, resulting in
IPSPs.

Removal of Neurotransmitter

Removal of neurotransmitter from the synaptic cleft is essential for normal

synaptic function to prevent indefinite influence on the postsynaptic cell.
Neurotransmitter is removed in three ways:

1. Diffusion: Neurotransmitter molecules diffuse away from the

synaptic cleft.

2. Enzymatic Degradation: Enzymes inactivate neurotransmitters.

 Example: Acetylcholinesterase breaks down acetylcholine.

3. Uptake by Cells:

 Reuptake: Neurotransmitters are actively transported back

into the neuron that released them.

 Uptake: Neurotransmitters are transported into neighbouring

neuroglia.

 Example: Neurons take up norepinephrine and recycle it into

new synaptic vesicles using neurotransmitter
transporters.