ORGANIZATION OF THE NERVOUS ■​ Axon. Transmits output signals.

SYSTEM, BASIC FUNCTIONS OF ➢​ Synaptic Connections

○​ Incoming signals enter primarily through
SYNAPSES, AND NEUROTRANSMITTERS
synapses on dendrites and cell bodies.
○​ Number of synaptic connections varies
■​ Few hundred to as many as
200,000, depending on neuron
type.
➢​ Signal Transmission
○​ Input direction – Synapses receive signals
from other neurons.
○​ Output direction – A single axon carries the
signal away.
■​ Axons may branch to reach
multiple targets within the nervous
system or peripheral body.
The nervous system stands out due to its unparalleled
➢​ One-Way Signal Flow
complexity, enabling intricate thought processes and control
○​ Synapses are specialized to allow signals to
mechanisms. It processes millions of sensory inputs every
move only in the forward direction
minute, integrating this information to direct appropriate
■​ From the axon of one neuron to the
responses throughout the body.
dendrites or cell body of the next.
○​ This ensures signals follow specific
GENERAL DESIGN OF THE NERVOUS SYSTEM
pathways to perform designated nervous
system functions.
CENTRAL NERVOUS SYSTEM NEURON: THE BASIC
FUNCTIONAL UNIT Neurons in the CNS demonstrate a highly organized structure,
The central nervous system (CNS) plays a crucial role in with synapses ensuring directional flow of information. This
coordinating the body's functions through its intricate network unidirectional signaling mechanism is critical for maintaining
of neurons. The structure and signal transmission of neurons functional pathways within the nervous system, enabling
within the CNS, highlighting their unique features and precise and efficient communication.
functional design.
SENSORY PART OF THE NERVOUS
SYSTEM—SENSORY RECEPTORS
The nervous system primarily begins its activities through
sensory experiences, which are detected by specialized
receptors across the body. These experiences either trigger
immediate responses or are stored as memories to influence
future reactions.

➢​ Neuron Composition
○​ CNS contains approximately 80–100 billion
neurons.
○​ A typical neuron consists of: Role of Sensory Receptors
■​ Dendrites. Receive incoming
➢​ Sensory experiences originate from specific
signals.
receptors,
■​ Cell body. Integrates inputs.
1
 ○​ Visual receptors (eyes). ■​ Secretion of chemicals by both
○​ Auditory receptors (ears). exocrine (e.g., sweat glands) and
○​ Tactile receptors (skin). endocrine glands (e.g., hormones).
○​ Other specialized sensory receptors. ○​ These activities are collectively termed
➢​ Responses to these experiences motor functions.
○​ Can lead to immediate brain reactions. ➢​ Effectors
○​ Can be stored as memories for minutes, ○​ Muscles and glands are the effectors,
weeks, or years, influencing future bodily responsible for carrying out the motor
reactions. functions dictated by the nervous system.
➢​ Motor Nerve Axis
Pathway of Sensory Information ○​ The skeletal motor nerve axis controls
skeletal muscle contraction (as shown in
➢​ The somatic sensory system collects sensory data Figure 46-3).
from the body’s surface and deeper structures. ○​ Parallel to this, the autonomic nervous
➢​ Information flows through peripheral nerves into system manages smooth muscles, glands,
the central nervous system (CNS). and other internal systems.
➢​ The CNS routes sensory input to multiple processing ➢​ Levels of CNS Control
areas, including ○​ Skeletal muscle control occurs at several
○​ Spinal cord (all levels). levels of the CNS
○​ Reticular substance (medulla, pons, and ■​ Spinal cord.
mesencephalon). ■​ Reticular substance (medulla,
○​ Cerebellum. pons, mesencephalon).
○​ Thalamus. ■​ Basal ganglia.
○​ Cerebral cortex. ■​ Cerebellum.
■​ Motor cortex.
Sensory receptors serve as the entry point for nervous system ○​ Lower CNS regions handle automatic,
activities, relaying crucial information to various CNS regions. instantaneous responses to sensory stimuli.
This efficient sensory processing allows for immediate ○​ Higher CNS regions manage deliberate,
responses or the creation of memories, ensuring adaptability complex muscle movements based on
and proper coordination of bodily functions. thought processes.

MOTOR PART OF THE NERVOUS The nervous system plays a critical role in controlling both
SYSTEM—EFFECTORS voluntary and involuntary muscle actions and glandular
secretions. This is achieved through a layered structure of
The nervous system plays a critical role in controlling bodily control centers, which ensure automatic responses as well as
activities by managing muscle contractions and glandular conscious, complex movements that allow the body to
secretions. These processes, known as the motor functions of function adaptively.
the nervous system, involve specialized anatomical structures
called effectors. PROCESSING OF INFORMATION— INTEGRATIVE
FUNCTION OF THE NERVOUS SYSTEM

A key role of the nervous system is to process sensory

information and generate appropriate mental and motor
responses. Most sensory input is filtered out as irrelevant, but
when important information is detected, the brain processes it
to trigger desired actions.

Processing of Sensory Information

➢​ More than 99% of sensory information is discarded

by the brain, as it is deemed irrelevant.
➢​ Examples of unnoticed stimuli
○​ Body parts in contact with clothing.
○​ Pressure from sitting on a seat.
○​ Perpetual background noise.

Selective Attention

➢​ Only important sensory information is processed

and brought to conscious attention.
➢​ For example, an object in one’s field of vision may
capture attention, or a sudden sensation may demand
➢​ Nervous System Control focus.
○​ The nervous system controls
■​ Skeletal muscle contraction Integrative Function of the Nervous System
throughout the body.
■​ Smooth muscle contraction within ➢​ When relevant sensory information is detected, it is
internal organs. processed and directed to appropriate brain regions
for integration and motor response.
➢​ Example:
2
 ○​ A person touching a hot stove ➢​ Each time sensory signals pass through synapses, the
■​ Instantaneous response: Lifting synapses become more capable of transmitting the
the hand away. same type of signal.
■​ Subsequent responses: Moving ➢​ This process is known as facilitation.
away from the stove, potentially
shouting in pain. Long-Term Facilitation

The nervous system efficiently filters out unnecessary sensory ➢​ After repeated passage through synapses, these
data, focusing on relevant stimuli and triggering appropriate synapses become so facilitated that internal brain
mental and physical reactions. This integrative function allows signals can trigger the transmission of impulses, even
for rapid responses to important events, ensuring survival and without sensory input.
adaptive behavior. ➢​ This results in the perception of experiencing the
original sensations, though they are actually just
ROLE OF SYNAPSES IN PROCESSING INFORMATION memories.

Synapses are crucial junctions between neurons that play a key Memory and Thinking
role in determining the direction and strength of neural
signals. They not only regulate signal transmission but also ➢​ The brain uses stored memories in its thinking
have the ability to selectively amplify or block signals processes, comparing new sensory experiences with
depending on various factors. past memories.
➢​ Memories help the brain select and channel important
➢​ Function of Synapses sensory information to appropriate areas for future
○​ Synapses act as the junction point between use or motor responses.
neurons, controlling how signals pass from
one neuron to the next. Uncertainty of Long-Term Facilitation Mechanism
○​ Transmission ease: Some synapses easily
transmit signals, while others transmit with ➢​ The exact mechanisms of long-term facilitation and
difficulty. sensory memory are still not fully understood, but
➢​ Influence of Facilitatory and Inhibitory Signals these processes are explored in Chapter 58.
○​ Facilitatory signals - Can open synapses to
Memory is a vital function of the nervous system, enabling the
allow transmission.
brain to store sensory information for future motor responses
○​ Inhibitory signals - Can close synapses,
and thinking. Through processes like facilitation, synapses
preventing signal transmission.
help the brain create perceptions from past experiences,
➢​ Response Variability of Postsynaptic Neurons
guiding future responses and decisions.
○​ Some postsynaptic neurons generate many
output impulses in response to signals.
MAJOR LEVELS OF CENTRAL NERVOUS SYSTEM
○​ Others produce only a few output impulses.
FUNCTION
➢​ Selective Action of Synapses
○​ Synapses can selectively block weak
The human nervous system has evolved through different
signals while allowing strong signals to
stages of human development, with each stage contributing
pass.
unique functional capabilities. These capabilities are organized
○​ At times, they amplify weak signals and
into three major levels within the central nervous system
may channel them in multiple directions
(CNS).
rather than just one.
The nervous system's evolution has led to the development of
Synapses play a selective and dynamic role in neural
three distinct levels in the CNS, each with specialized roles
communication. They regulate the flow of signals by adjusting
that contribute to the complexity and functionality of human
their transmission capacity, amplifying important signals, and
behavior and bodily regulation.
directing them efficiently through the nervous system.
SPINAL CORD LEVEL

While the spinal cord is often thought of as merely a conduit

STORAGE OF INFORMATION—MEMORY
for signals between the body and brain, it actually plays a
much more active and independent role in controlling various
While only a small fraction of sensory information leads to
bodily functions.
immediate motor responses, much of the information is stored
for future use in motor control and thinking. The process of
Spinal Cord's Independent Functions
storing sensory information, known as memory, is a key
function of synapses in the brain. ➢​ Even after injury to the high neck region, where the
spinal cord is cut, many essential functions remain
Memory and Storage
possible. These functions include:
○​ Walking movements. Coordinated by
➢​ Memory involves storing information for later use,
neuronal circuits in the spinal cord.
primarily in the cerebral cortex, but also in the basal
○​ Pain withdrawal reflexes. Automatically
brain regions and spinal cord.
pulling the body away from harmful stimuli.
○​ Leg stiffening reflexes. Helping to support
Facilitation
the body against gravity.
○​ Control of local physiological functions:

3
 ■​ Including regulating blood vessels, ➢​ Collaboration with Lower Centers The cortex never
gastrointestinal movements, and functions in isolation; it works with lower brain
urinary excretion. centers to refine and make their functions more
precise.
➢​ Without the cortex, lower brain functions would be
imprecise or incomplete.
➢​ Converting Functions to Precise Operations The
cortical information enhances and sharpens lower
Control of Spinal Cord by Higher Brain Levels brain functions, making them more determined and
effective.
○​ The brain does not always directly send
signals to the body; often, it sends Cerebral Cortex and Thought Processes
commands to the spinal cord control centers
to manage these functions autonomously. ➢​ The cortex is essential for thought but relies on the
lower brain centers to initiate wakefulness, which
The spinal cord is not merely a signal conduit but an active allows access to the memory bank necessary for
control center capable of managing critical bodily functions. thought processes.
The brain influences the spinal cord by directing it to carry out ➢​ The lower brain centers are responsible for
various actions, allowing for coordinated responses even awakening the cerebral cortex and enabling access to
without direct brain involvement. memories.

LOWER BRAIN OR SUBCORTICAL LEVEL The cerebral cortex is indispensable for thought and memory,
but it depends on the lower brain centers for activation and
Many subconscious bodily functions are controlled by the coordination. Together, these brain regions work in harmony,
lower regions of the brain, which include areas responsible for with the cortex transforming stored information into
autonomic activities like respiration, emotion, and reflexive purposeful actions and precise thoughts.
behaviors.
COMPARISON OF THE NERVOUS SYSTEM TO A
➢​ Subconscious Activities and Brain Areas COMPUTER
○​ Medulla, Pons, and Mesencephalon Key
areas for controlling unconscious functions, There are significant parallels between the structure of
such as: computers and the human nervous system. Both share input
■​ Arterial pressure and respiration. and output systems, and as computers become more complex,
■​ Equilibrium (in coordination with their functions become increasingly analogous to those of the
the cerebellum). brain.
○​ Cerebellum and Reticular Substance
■​ Responsible for equilibrium The human brain and computers share structural similarities,
control in conjunction with other especially in how they process input, store information, and
lower brain structures. direct output. The brain, much like a computer, continuously
○​ Feeding Reflexes integrates sensory data with memory to guide bodily functions
■​ Salivation and lip licking in and thought processes.
response to food taste are
controlled by the medulla, pons,
mesencephalon, amygdala, and
hypothalamus.
➢​ Emotional Responses
○​ Emotions such as anger, excitement, sexual
response, and reactions to pain or pleasure
can still occur even after substantial damage
to the cerebral cortex.

The lower regions of the brain are essential for regulating

subconscious bodily functions, including vital autonomic
processes and emotional responses. These functions can
persist even if higher brain areas, like the cerebral cortex, are
impaired.

HIGHER BRAIN OR CORTICAL LEVEL

CENTRAL NERVOUS SYSTEM SYNAPSES

The cerebral cortex plays a critical role in higher brain

Information in the central nervous system is transmitted
functions, particularly in memory and thought processes,
through nerve impulses, which travel from neuron to neuron.
while working in coordination with the lower brain centers for
However, the transmission of these impulses can be altered in
precise and effective operation.
various ways.

Role of the Cerebral Cortex

TYPES OF SYNAPSES—CHEMICAL AND ELECTRICAL

➢​ Memory Storehouse The cortex serves as an

There are two main types of synapses: chemical and
extensive storehouse of information, crucial for
electrical. Chemical synapses are the primary mode of signal
guiding brain functions.
transmission in the human central nervous system, while
electrical synapses have a different mechanism of action.
4
Chemical Synapses ➢​ Parts
-​ The motor neuron has three main parts:
➢​ In these synapses, the presynaptic neuron releases a ○​ Soma The main body of the neuron.
neurotransmitter that acts on the postsynaptic ○​ Axon Extends from the soma into a
neuron to excite, inhibit, or modify its sensitivity. peripheral nerve.
➢​ Neurotransmitters Over 50 neurotransmitters exist, ○​ Dendrites Branching projections from the
including acetylcholine, norepinephrine, serotonin, soma, extending up to 1 millimeter into the
and glutamate. surrounding areas.
➢​ One-Way Transmission Chemical synapses have a ➢​ Synaptic Terminals
critical feature of one-way conduction, where ○​ The dendrites and soma are covered with
signals always travel from the presynaptic neuron to 10,000 to 200,000 synaptic knobs
the postsynaptic neuron. This ensures directed (presynaptic terminals), with 80% to 95% on
transmission of signals for precise control over the dendrites.
functions such as sensation, motor control, and ○​ Excitatory terminals release
memory. neurotransmitters that excite the neuron,
while inhibitory terminals release
Electrical Synapses neurotransmitters that inhibit it.

➢​ Electrical synapses involve gap junctions, which are Variations in Neurons

ion channels connecting adjacent cells, allowing ions
to flow freely between them. ➢​ Neurons in other parts of the nervous system differ
➢​ Bidirectional Transmission Unlike chemical from motor neurons in:
synapses, electrical synapses allow signals to be ○​ The size of the cell body.
transmitted in both directions. ○​ The length and number of dendrites.
➢​ Role in Coordination Electrical synapses help ○​ The length and size of the axon.
synchronize the activity of large groups of ○​ The number of presynaptic terminals,
interconnected neurons, allowing for synchronous which can vary from a few to over 200,000.
firing and heightened sensitivity.
Presynaptic Terminals
Chemical synapses are crucial for focused, one-way
transmission of signals in the nervous system, while electrical ➢​ These terminals are usually round or oval knobs
synapses allow for bidirectional communication and (synaptic knobs), and their structure is important for
coordination. Both types of synapses contribute to the overall synaptic function.
functioning and integration of neural activity. ➢​ Electron microscopy reveals that each terminal
contains:
PHYSIOLOGIC ANATOMY OF THE SYNAPSE ○​ Transmitter vesicles: Contain
neurotransmitters that are released into the
the structure of an anterior motor neuron in the spinal cord, synaptic cleft to excite or inhibit the
focusing on its parts, synaptic terminals, and their role in postsynaptic neuron.
neuronal communication. ○​ Mitochondria: Provide ATP for the
synthesis of neurotransmitters.
➢​ Mechanism of Transmission:
○​ When an action potential spreads to the
presynaptic terminal, depolarization causes
some vesicles to release neurotransmitters
into the synaptic cleft.
○​ These neurotransmitters bind to receptors on
the postsynaptic neuron, changing its
permeability and either exciting or inhibiting
it, depending on the type of receptor.

TRANSMITTER RELEASE FROM PRESYNAPTIC

TERMINALS—ROLE OF CALCIUM IONS

The presynaptic terminal plays a crucial role in the

transmission of signals between neurons. The release of
neurotransmitters, which enables communication between
neurons, is a well-coordinated process primarily controlled by
calcium ions. Below is an overview of how this process
works.

Presynaptic Membrane and Calcium Channels

➢​ The presynaptic membrane contains voltage-gated

calcium channels.
➢​ When an action potential depolarizes the presynaptic
membrane, these calcium channels open.

Structure of Anterior Motor Neurons Calcium Ion Influx

5
 ➢​ The opening of the channels allows calcium ions to second messengers that trigger intracellular signaling
flow into the terminal. pathways, influencing cellular processes.
➢​ The amount of neurotransmitter released from the
terminal into the synaptic cleft is directly related to Postsynaptic receptors are integral to the transmission of
the number of calcium ions entering. signals in the nervous system. They either directly control ion
channels or use second messenger systems to regulate cellular
Mechanism of Neurotransmitter Release activity. These mechanisms ensure precise modulation of
neuronal functions in response to neurotransmitter signals.
➢​ Upon entering the presynaptic terminal, calcium ions
bind to protein molecules known as release sites on ION CHANNELS
the inner surface of the membrane.
➢​ This binding causes the release sites to open, The ion channels in the postsynaptic membrane are
allowing vesicles filled with neurotransmitters to specialized to regulate the flow of specific ions, which is vital
release their contents into the synaptic cleft. for controlling neuronal activity. The precise selectivity of
➢​ Each vesicle contains 2,000 to 10,000 molecules of these channels ensures the proper transmission of electrical
acetylcholine. signals in the nervous system.

Vesicle Storage and Transmission Capacity

➢​ The presynaptic terminal contains enough vesicles to

transmit signals from a few hundred to over 10,000
action potentials.

The process of neurotransmitter release in the presynaptic

terminal is highly dependent on calcium ions. These ions
trigger the release of neurotransmitters from vesicles, which is
essential for effective neuronal communication. This
mechanism ensures the precise transmission of signals across
synapses and supports the efficient function of the nervous
system.

TRANSMITTER ACTIONS ON POSTSYNAPTIC

NEURONS—FUNCTION OF RECEPTOR PROTEINS
EXCITATORY OR INHIBITORY RECEPTORS IN THE
The postsynaptic neuron is equipped with specialized POSTSYNAPTIC MEMBRANE
receptors that play a pivotal role in receiving neurotransmitter
signals from the presynaptic neuron. These receptors facilitate Postsynaptic receptors play a vital role in determining whether
communication across the synapse by controlling ion channels a neuron becomes excited or inhibited. This distinction
or activating intracellular processes. between excitation and inhibition is crucial for regulating
nervous system function and maintaining a balance between
Receptor Structure stimulating and restraining neural activity.

➢​ The postsynaptic membrane contains receptor Excitation Mechanisms

proteins that have two key components
○​ Binding component Extends outward into 1.​ Opening of sodium channels
the synaptic cleft and binds with the ○​ Sodium ions flow into the postsynaptic
neurotransmitter from the presynaptic neuron, making the membrane potential
terminal. more positive and moving it closer to the
○​ Intracellular component Passes through the threshold for action potential generation.
postsynaptic membrane, extending into the ○​ This is the most common method of
interior of the neuron. excitation.
2.​ Depressed conduction through chloride or
Receptor Activation and Ion Channel Control potassium channels
○​ Decreasing chloride ion influx or potassium
➢​ When neurotransmitters bind to receptors, they can ion efflux increases the positive charge
trigger one of two responses: inside the cell, promoting excitation.
○​ Direct gating of ion channels Receptors 3.​ Changes in internal metabolism
open ion channels to allow specific ions to ○​ Modifying cell activity or receptor numbers
pass through the membrane. can enhance excitation by increasing
○​ Activation of second messengers Some excitatory receptors or reducing inhibitory
receptors activate molecules inside the cell receptors.
that influence cellular functions.
Inhibition Mechanisms
Types of Receptors
1.​ Opening of chloride ion channels
➢​ Ionotropic receptors These receptors directly control ○​ Chloride ions flow into the postsynaptic
ion channels, allowing the flow of ions in response to neuron, making the internal membrane
neurotransmitter binding. potential more negative and inhibiting the
➢​ Metabotropic receptors These receptors do not neuron.
directly control ion channels but instead activate 2.​ Increase in potassium conductance

6
 ○​ Potassium ions move out of the neuron, ○​ These transmitters are responsible for fast,
increasing internal negativity, which inhibits acute responses in the nervous system.
the neuron. ○​ They are involved in processes like the
3.​ Activation of receptor enzymes transmission of sensory signals to the brain
○​ Inhibits cellular metabolic processes, which and motor signals to muscles.
can increase inhibitory receptor numbers or 2.​ Neuropeptides
decrease excitatory receptor numbers. ○​ These are larger molecules that typically
cause slower, more prolonged effects.
CHEMICAL SUBSTANCES THAT FUNCTION AS ○​ They can induce long-term changes in the
SYNAPTIC TRANSMITTERS nervous system, such as altering receptor
numbers, modulating ion channel activity,
Synaptic transmission involves a variety of chemical and potentially influencing synapse structure
substances that facilitate communication between neurons. and quantity.
These substances can be classified into two major categories: 3.​ Gaseous Molecules (e.g., NO, H2S, CO)
small-molecule, rapidly acting transmitters, and large ○​ While their role as neurotransmitters is still
neuropeptides that act more slowly. Some gaseous molecules debated, they may act as modulators in
are also involved, though their roles remain somewhat synaptic transmission.
uncertain.
Synaptic transmitters are essential for both fast and
long-lasting effects in the nervous system. Small-molecule
transmitters handle quick responses, while neuropeptides
mediate prolonged actions that can lead to structural changes
in the brain. The potential involvement of gaseous molecules
suggests additional layers of complexity in neurotransmission.

SMALL-MOLECULE, RAPIDLY ACTING

TRANSMITTERS

Small-molecule neurotransmitters play a crucial role in

synaptic transmission by facilitating rapid communication
between neurons. These molecules are synthesized in the
presynaptic terminal, released in response to action potentials,
and act on postsynaptic receptors to induce either excitation or
inhibition.

Synthesis and Release

➢​ Small-molecule neurotransmitters are synthesized in

the presynaptic terminal and stored in vesicles.
➢​ Upon the arrival of an action potential, vesicles
release their contents into the synaptic cleft, where
they rapidly bind to receptors on the postsynaptic
neuron.
➢​ The effect is usually quick, often occurring in less
than a millisecond.

Recycling of Vesicles

➢​ After the release of neurotransmitters, vesicles are

recycled. The membrane becomes part of the synaptic
membrane and later invaginates to form new vesicles.
➢​ This recycling process ensures efficient
neurotransmitter release.

Acetylcholine

➢​ Synthesized in the presynaptic terminal and plays a

significant role in various parts of the nervous
system, including motor control and the autonomic
nervous system.
➢​ It can have excitatory effects, such as in skeletal
muscle, or inhibitory effects, such as in
parasympathetic nerve endings (e.g., the vagus
nerve's effect on the heart).

Other Small-Molecule Neurotransmitters

Types of Synaptic Transmitters
➢​ Norepinephrine Involved in regulating wakefulness
1.​ Small-Molecule, Rapidly Acting Transmitters and mood. It is secreted by neurons in the brainstem

7
 and hypothalamus and by postganglionic neurons of packaged into vesicles for transport to the nerve
the sympathetic nervous system. terminals.
➢​ Dopamine Released from the substantia nigra, it ➢​ The vesicles are transported slowly (a few
plays a role in motor control and emotional centimeters per day) by axonal streaming, and they
responses, typically having an inhibitory effect. release their contents at the synaptic terminal in
➢​ Glycine An inhibitory neurotransmitter mainly found response to action potentials.
in the spinal cord.
➢​ GABA (Gamma-Aminobutyric Acid) The primary Characteristics of Neuropeptides
inhibitory neurotransmitter in the adult central
nervous system, though it acts as an excitatory ➢​ Slow Synthesis Due to their complex synthesis and
neurotransmitter during early brain development. transport process, much smaller quantities of
➢​ Glutamate The main excitatory neurotransmitter, neuropeptides are released compared to
important in sensory pathways and the cerebral small-molecule transmitters.
cortex. ➢​ Potency Neuropeptides are much more potent, often a
➢​ Serotonin Regulates mood, sleep, and pain thousand times more than small-molecule
perception. It has inhibitory effects in certain regions transmitters, compensating for their smaller quantity.
of the nervous system. ➢​ Prolonged Effects Neuropeptides induce prolonged
➢​ Nitric Oxide A gaseous neurotransmitter involved in actions, such as lasting changes in calcium channel
long-term behavior and memory functions. Unlike activity, alterations in cellular metabolism, and gene
other neurotransmitters, it is not stored in vesicles activation/deactivation. These effects can last from
and diffuses directly into postsynaptic neurons to days to years.
modify intracellular functions.
Co-Localization and Co-Release with Small-Molecule
Small-molecule neurotransmitters are essential for rapid Transmitters
communication in the nervous system, influencing both
short-term and long-term neuronal functions. Their roles range ➢​ Neuropeptides are often co-localized with
from excitation and inhibition to modulation of behavior and small-molecule neurotransmitters within the same
memory, highlighting the complexity and adaptability of neurons.
synaptic transmission in the brain. ➢​ In some cases, they are stored and released together
in the same synaptic vesicles, while in other cases,
NEUROPEPTIDE they are housed in separate vesicles but released
Neuropeptides are a distinct class of neurotransmitters concurrently.
synthesized and released in a manner different from ➢​ The co-release of these neurotransmitters can
small-molecule transmitters. These transmitters typically have influence postsynaptic neurons in complex ways,
slower and longer-lasting effects and can coexist with where the fast-acting small molecules may trigger
small-molecule neurotransmitters in the same neurons, immediate responses, while neuropeptides initiate
influencing a variety of neuronal processes. longer-term effects through second messenger
systems or gene expression changes.

Example of Co-Release

➢​ In the raphe nucleus of the brainstem, neurons

co-release serotonin and glutamate, both of which
play significant roles in regulating sleep-wake cycles.
This co-release allows for a balance of immediate
signaling and long-term modulation.

Neuropeptides offer a unique mode of synaptic signaling,

providing slow, prolonged effects that contrast with the rapid
actions of small-molecule transmitters. The coexistence and
co-release of these two types of transmitters allow neurons to
modulate both short-term and long-term processes, enhancing
the complexity and flexibility of neural communication.

ELECTRICAL EVENTS DURING NEURONAL

EXCITATION
the process of neuronal excitation and the role of excitatory
postsynaptic potentials (EPSPs) in initiating action potentials.
It also explains the concept of summation and how the action
potential is generated at the initial segment of the axon.

Synthesis of Neuropeptides

➢​ Neuropeptides are synthesized in the neuronal cell

body, not in the presynaptic terminal.
➢​ Large-protein molecules are created by ribosomes,
which are then processed in the endoplasmic
reticulum and Golgi apparatus.
➢​ These proteins are split enzymatically to form
neuropeptides or their precursors, and subsequently

8
 ELECTRICAL EVENTS DURING NEURONAL
INHIBITION
The effects of inhibitory synapses, presynaptic inhibition,
and the summation of postsynaptic potentials on neuronal
excitation. It covers how inhibitory signals reduce the
likelihood of a neuron firing and the different types of
summation (spatial and temporal) that lead to neuron
excitation.

Inhibitory Postsynaptic Potential (IPSP)

Excitatory Postsynaptic Potential (EPSP)
➢​ Inhibitory synapses open chloride channels,
➢​ The membrane potential increases from −65 mV to allowing chloride ions to enter the neuron, making
−45 mV, making the neuron more positive (less the membrane potential more negative
negative). (hyperpolarization).
➢​ This increase is called the EPSP, and if it rises high ➢​ The Nernst potential for chloride is approximately
enough, it can trigger an action potential in the −70 mV, which is more negative than the typical −65
postsynaptic neuron. mV resting potential.
➢​ An EPSP of +20 mV (from the resting potential) can ➢​ The entry of chloride ions (influx) or the exit of
initiate this process. potassium ions (efflux) results in a hyperpolarized
membrane, which is termed IPSP. The membrane
Summation potential may change by about −5 mV to inhibit the
neuron.
➢​ A single presynaptic terminal cannot generate a large
enough EPSP to reach the threshold for an action Presynaptic Inhibition
potential.
➢​ Instead, multiple presynaptic terminals (about ➢​ Inhibitory substances, such as GABA, can be
40-80 for motor neurons) discharge simultaneously or released onto the presynaptic terminals, causing the
in rapid succession, a process called summation. influx of chloride ions.
➢​ This reduces the effect of sodium ions that would
Generation of Action Potentials normally cause depolarization, preventing signal
transmission from the presynaptic to the postsynaptic
➢​ Once the EPSP reaches the required threshold, an
neuron.
action potential is generated in the initial segment of
the axon. Time Course of Postsynaptic Potentials
➢​ The soma has fewer voltage-gated sodium channels,
making it difficult for the EPSP to generate an action ➢​ EPSPs and IPSPs are short-lived, lasting 1-2
potential there. milliseconds before returning to the resting
➢​ The initial axon segment has a high concentration of membrane potential.
sodium channels, making it easier to trigger an action ➢​ Some transmitter substances can cause more
potential. prolonged effects, lasting hundreds of milliseconds
➢​ The threshold for excitation is around −45 mV, to hours, especially neuropeptides.
with an EPSP of +20 mV.
Spatial Summation
Action Potential Propagation
➢​ A single presynaptic terminal often does not excite a
➢​ Once initiated, the action potential travels down the neuron sufficiently.
axon and may also move backward toward the soma ➢​ Spatial summation occurs when multiple
and dendrites. presynaptic terminals stimulate the neuron
➢​ However, dendrites typically cannot generate action simultaneously, increasing the postsynaptic potential
potentials because they also have few voltage-gated and eventually reaching the threshold for action
sodium channels. potential initiation.

EPSP can lead to the generation of an action potential in a Temporal Summation

neuron through the processes of summation and the high
concentration of sodium channels in the initial axon segment. ➢​ Temporal summation occurs when rapid, successive
This process is crucial for neuronal excitation and discharges from the same presynaptic terminal add
communication within the nervous system. up, increasing the postsynaptic potential.

9
 ➢​ If the rate of stimulation is high enough, this can lead sodium channels and have a high threshold for
to neuronal excitation. excitation.
➢​ However, dendrites can conduct signals through
Simultaneous Summation of EPSP and IPSP electrotonic conduction, a process that transmits
electrical current via ion flow within the dendrites
➢​ If both EPSP and IPSP are active at the same time, without generating action potentials.
their effects may cancel each other out, preventing
the neuron from firing. Decrement of Electrotonic Conduction

Facilitation of Neurons ➢​ The electrotonic current in dendrites decays as it

travels toward the soma due to the dendrites'
➢​ Facilitation occurs when a neuron is close to the leakiness to ions (e.g., potassium and chloride).
threshold for firing but hasn’t reached it. Another ➢​ This decremental conduction means that the farther
excitatory signal can push the neuron past the an excitatory synapse is from the soma, the weaker
threshold, leading to action potential generation. the signal becomes before reaching the soma.
➢​ This allows neurons to be easily activated in ➢​ Consequently, synapses near the soma have a much
response to further excitatory inputs. stronger impact on neuronal excitation or inhibition
than those located further away.
Inhibition and summation play crucial roles in the regulation
of neuronal firing. Inhibitory synapses reduce neuron Summation of Excitation and Inhibition in Dendrites
excitability, while spatial and temporal summation of
postsynaptic potentials increase the likelihood of action ➢​ Dendrites can summate both excitatory
potential initiation. Additionally, facilitation allows neurons postsynaptic potentials (EPSPs) and inhibitory
to respond quickly to further stimuli, enabling efficient postsynaptic potentials (IPSPs), similar to the
communication within the nervous system. soma.
➢​ In the example provided, a dendrite receives a strong
SPECIAL FUNCTIONS OF DENDRITES FOR EXCITING EPSP near its tip and inhibitory signals closer to the
NEURONS soma, resulting in the cancellation of the excitatory
The spatial field of excitation of dendrites in anterior motor effect by the inhibitory input.
neurons, the limitations of dendrites in transmitting action ➢​ Inhibition on the axon hillock and initial axon
potentials, and the processes of electrotonic conduction and segment is especially powerful because it directly
decremental conduction that occur within dendrites. It also increases the threshold for excitation at the critical
discusses the summation of excitatory and inhibitory signals point where action potentials are initiated.
and how synaptic locations influence neuronal activity.

Dendrites play a crucial role in the spatial summation of

synaptic signals, though they cannot generate action potentials
on their own. Their ability to conduct signals electrotonically
allows for the integration of excitatory and inhibitory inputs.
The proximity to the soma determines the influence of
synaptic signals, with signals closer to the soma having a more
significant effect. Additionally, inhibitory inputs at key
locations, such as the axon hillock, can regulate neuronal
excitability by altering the threshold for action potential
initiation.

EXCITATION STATE OF THE NEURON AND RATE OF

FIRING
The concept of the "excitatory state" in neurons, explaining
how the balance between excitation and inhibition determines
a neuron's firing behavior. It also explores the variability in
thresholds for excitation and maximum firing frequencies
across different neurons and their implications for nervous
Large Spatial Field of Excitation in Dendrites system functions.

➢​ Dendrites of anterior motor neurons can extend 500

to 1000 micrometers, covering a large area.
➢​ 80% to 95% of all presynaptic terminals of the
motor neuron terminate on dendrites, contributing
significantly to excitation.
➢​ The extensive dendritic network allows for the
summation of signals from multiple presynaptic
nerve fibers.

Dendrites and Action Potentials

➢​ Dendrites generally cannot transmit action

potentials because they lack sufficient voltage-gated

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 SPECIAL CHARACTERISTICS OF SYNAPTIC
TRANSMISSION

There are several factors that influence synaptic transmission,

including synaptic fatigue, the effects of pH changes,
hypoxia, and various drugs. It also delves into synaptic delay
and its importance in understanding neuronal activity.

Fatigue of Synaptic Transmission

➢​ Synaptic fatigue occurs when excitatory synapses

are repetitively stimulated, initially causing high
discharge rates that gradually decrease.
➢​ Fatigue acts as a protective mechanism, reducing
excess neuronal activity, as seen in the termination of
epileptic seizures.
Excitatory and Inhibitory States
➢​ The primary cause of fatigue is the exhaustion of
neurotransmitter stores in presynaptic terminals,
➢​ A neuron's excitatory state is the result of the
which can last from a few seconds to minutes of rapid
combined summation of excitatory and inhibitory
stimulation.
inputs.
➢​ Other factors contributing to fatigue include:
➢​ If the excitation surpasses inhibition, the neuron is
○​ Inactivation of postsynaptic membrane
in an excitatory state.
receptors.
➢​ If inhibition dominates, the neuron is in an inhibitory
○​ Abnormal ion concentrations in
state.
postsynaptic cells.
Thresholds and Firing Behavior
Effect of Acidosis or Alkalosis
➢​ When the excitatory state exceeds the threshold for
➢​ Alkalosis increases neuronal excitability, which can
excitation, the neuron will fire repetitively as long as
lead to conditions like epileptic seizures due to a rise
the excitation remains high.
in blood pH.
➢​ Neurons have different thresholds for excitation, with
➢​ Acidosis decreases neuronal excitability and can lead
some neurons requiring less excitation to reach their
to coma in cases of severe diabetic or uremic
threshold, while others need more.
acidosis.
➢​ For example, neuron 1 has a low threshold for
➢​ Certain substances like caffeine, theophylline, and
excitation, while neuron 3 has a high threshold.
theobromine increase neuronal excitability by
Frequency of Firing lowering the threshold for excitation.
➢​ Strychnine raises neuronal excitability by inhibiting
➢​ The maximum frequency of firing varies among the action of inhibitory neurotransmitters, leading
neurons. to tonic muscle spasms.
➢​ Neuron 2, for instance, has the lowest maximum
frequency of discharge, whereas neuron 3 can fire at Effect of Hypoxia on Synaptic Transmission
a higher maximum frequency.
➢​ Neurons are highly sensitive to oxygen levels. A lack
➢​ Neurons can fire continuously if their normal
of oxygen (hypoxia) for even a few seconds can
excitatory state is above their threshold level. Their
cause complete loss of excitability, leading to
firing rate can be increased by increasing excitation
unconsciousness if brain blood flow is temporarily
or decreased by applying inhibition.
interrupted.
Implications of Different Neuronal Responses
Effect of Drugs on Synaptic Transmission
➢​ The diversity of neuronal responses allows the
➢​ Anesthetics typically increase the threshold for
nervous system to perform various functions, as
excitation, decreasing synaptic transmission by
different neurons can have varying thresholds for
altering the physical properties of neuronal
excitation and different maximum firing rates.
membranes.
➢​ The ability to adjust a neuron's excitatory and
➢​ Other drugs, like caffeine and certain stimulants,
inhibitory states enables complex control over its
increase excitability, while some inhibit the activity
firing patterns, which is crucial for coordinated and
of inhibitory transmitters.
flexible nervous system function.
Synaptic Delay
Neurons operate in an excitatory state when the excitation
level exceeds inhibition, leading to repetitive firing once the
➢​ Synaptic delay refers to the time consumed during
threshold is reached. Neurons differ in their thresholds for
the transmission of signals from a presynaptic to a
excitation and firing frequencies, allowing for diverse
postsynaptic neuron.
responses to stimuli. These variations are essential for the
➢​ The minimal time required for all processes
flexible and efficient functioning of the nervous system, as
(neurotransmitter release, diffusion, receptor action,
different neurons can handle different types of inputs and
etc.) is about 0.5 milliseconds.
perform specialized roles.
➢​ Measuring synaptic delay helps estimate the
number of neurons involved in a neuronal circuit,

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 providing insights into the speed and efficiency of
synaptic transmission.

Synaptic transmission is influenced by various physiological

and pathological factors such as fatigue, acidosis/alkalosis,
hypoxia, and drugs. Fatigue serves as a protective
mechanism against excessive neuronal activity, while changes
in pH and oxygen levels can either increase or decrease
neuronal excitability. Synaptic delay is crucial for
understanding the time dynamics of signal transmission,
aiding in the study of neural circuits.

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