Freberg pp.

2-3; 64-76

Neuroscience as an Interdisciplinary Field

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● Neuroscience encompasses the scientific study of the brain and nervous system,
exploring both health and disease through various analytical approaches such as
molecular, cellular, and behavioral methods.
● This field is likened to Google Earth, allowing scientists to view both minute
details (molecular level) and broader contexts (whole networks).
● Molecular neuroscience investigates the nervous system's structure at the
molecular level, focusing on DNA, RNA, and proteins.
● Cellular neuroscience examines the structure and function of individual nerve
cells, while synaptic neuroscience studies how these cells forge connections and
the dynamics of synapses crucial for learning and memory.
● Behavioral neuroscience emphasizes understanding the biological basis of
behavior, and its subfields include cognitive neuroscience—focusing on
information processing and decision-making—and social neuroscience, which
addresses the interplay between the nervous system and social behavior.
The Importance of Behavioral Neuroscience
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● Behavioral neuroscience, also referred to as biological psychology, integrates
findings from molecular, cellular, and network neuroscience to understand health
and illness.
● There is a critical need for this understanding due to the prevalence of
neurological illnesses, affecting one in six Americans and costing over $500
billion annually.
● Delaying conditions such as Alzheimer’s disease by five years could significantly
reduce healthcare costs, highlighting the connection between biology, behavior,
and health.
● Acknowledging the biological basis for behavior is increasingly important in
medical education, as seen in the MCAT's inclusion of psychology and behavioral
neuroscience content.
Historical Highlights in Neuroscience
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● The development of neuroscience is closely tied to advancements in technology
and methodology for studying the nervous system, historically hindered by
religious and scientific restrictions.
● Ancient practices such as trepanation (drilling holes in the skull) indicate an early
understanding of the brain's significance in health.

Opportunities in Neuroscience Careers

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● The field of neuroscience offers diverse career paths, often favoring individuals
with advanced education like MDs or PhDs, though opportunities also exist for
those with undergraduate degrees.
● Graduates can work as research assistants, substance abuse counselors, or in
mental health facilities, with growing roles in advertising and web design
leveraging neuroscience insights.
● Skills in science, research methods, mathematics, and statistics are vital for any
student pursuing a career in neuroscience.

Glia and Neurons

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● The nervous system is composed of two primary cell types: glia (support cells)
and neurons (information processing cells).
 ● Glial cells, including astrocytes, oligodendrocytes, and Schwann cells, perform
various supportive functions such as nutrient transfer, forming the blood-brain
barrier, and myelination of axons.
● Astrocytes are crucial for the structural support of neurons, manage nutrient
supply, and play roles in neurotransmitter regulation, but can also hinder neural
recovery following injury.
● Microglia act as the brain's cleanup crew by removing dead cells and debris, with
dysfunction linked to neurodegenerative diseases.
Briefly explain more about Glia and Neurons... The nervous system is composed of two
primary cell types: glia (support cells) and neurons (information processing cells). Glial
cells, including astrocytes, oligodendrocytes, and Schwann cells, perform various
supportive functions such as nutrient transfer, forming the blood-brain barrier, and
myelination of axons. Astrocytes are crucial for the structural support of neurons,
manage nutrient supply, and play roles in neurotransmitter regulation, but can also
hinder neural recovery following injury. Microglia act as the brain's cleanup crew by
removing dead cells and debris, with dysfunction linked to neurodegenerative diseases.
The nervous system is fundamentally structured around two main types of cells: glia and
neurons.

Glia (Support Cells)

Glial cells, often referred to as "glia," serve essential supportive roles for neurons. They can be
categorized into several types:

1. Astrocytes: These star-shaped cells are the most abundant glial cells in the brain. They
provide structural support to neurons, regulate the supply of nutrients, and maintain the
blood-brain barrier, which protects the brain from harmful substances in the blood. Astrocytes
also play a role in neurotransmitter regulation and can influence synaptic activity. However, in
response to neuronal injury, they can form scar tissue that inhibits neural regrowth, complicating
recovery.

2. Oligodendrocytes: Found in the central nervous system (CNS), oligodendrocytes are

responsible for the formation of myelin, a fatty substance that insulates axons and enhances the
speed of electrical signal transmission. Each oligodendrocyte can myelinate multiple axons from
different neurons.

3. Schwann Cells: These cells perform a similar myelinating function in the peripheral nervous
system (PNS). Unlike oligodendrocytes, each Schwann cell myelinates only a single segment of
one axon, requiring many Schwann cells to myelinate a single nerve.

4. Microglia: These are the brain's immune cells, acting as the cleanup crew by removing dead
cells and debris resulting from injury or disease. They are crucial for maintaining brain health,
but when activated excessively, they can contribute to inflammation and damage, which is
associated with neurodegenerative diseases like Alzheimer's and Parkinson's.

Neurons (Information Processing Cells)

Neurons are specialized cells responsible for processing and transmitting information
throughout the nervous system. They can be classified based on their structure and function:

1. Structure: Neurons typically consist of a cell body (soma), dendrites, and an axon. Dendrites
receive signals from other neurons, while the axon transmits signals away from the cell body to
other neurons or muscles.

2. Types of Neurons:
- Sensory Neurons: These neurons carry information from sensory receptors (e.g., for touch,
vision, and hearing) to the central nervous system.
- Motor Neurons: They transmit commands from the central nervous system to muscles and
glands, facilitating movement and bodily functions.
- Interneurons: These neurons serve as connectors between sensory and motor neurons,
playing a critical role in reflexes and complex processing tasks.

The interplay between glia and neurons is vital for the overall functioning of the nervous system,
influencing everything from basic reflexes to complex behaviors and cognitive functions.
Understanding these cells and their interactions is crucial for advancing treatments for various
neurological disorders.

Briefly explain more about Neuron Structure and Function ... Neurons are specialized
for communication, featuring structures like axons, which send signals, and dendrites,
which receive information. The neural membrane comprises a phospholipid bilayer with
embedded ion channels and pumps that regulate ion movement and maintain cellular
homeostasis. Key structures in the cytoskeleton, such as microtubules, facilitate the
transport of materials within the neuron and provide structural integrity needed for
function. Pathogens can exploit the neuron’s transport systems to infect the nervous
system, underscoring the neuron’s vulnerability.
Neurons are the fundamental units of the nervous system, specialized for communication and
information processing. Their structure is intricately designed to facilitate these functions,
comprising several key components:
1. Dendrites: These are tree-like branches that extend from the neuron’s cell body. Dendrites
receive signals from other neurons, allowing for the integration of information. The greater the
surface area of dendrites, the more synapses they can form, enhancing the neuron's ability to
process incoming signals.

2. Cell Body (Soma): The cell body contains essential organelles, including the nucleus,
ribosomes, and mitochondria, which are crucial for the neuron's metabolic activities and protein
synthesis. It serves as the site for synapses where communication with other neurons occurs.

3. Axon: This long, slender projection transmits electrical impulses away from the cell body to
other neurons, muscles, or glands. The axon begins at the axon hillock, where action potentials
are generated. Axons can vary in length and diameter, influencing the speed of signal
transmission.

4. Myelin Sheath: Many axons are insulated by a fatty layer known as myelin, which enhances
the speed and efficiency of electrical signaling. Myelin is segmented, with gaps known as nodes
of Ranvier that facilitate rapid signal conduction through a process called saltatory conduction.

5. Axon Terminals: At the end of the axon, terminals release neurotransmitters into the synaptic
gap, facilitating communication with adjacent neurons. These terminals contain synaptic
vesicles that store neurotransmitters, which are critical for transmitting signals across synapses.

6. Cytoskeleton: The neuron's cytoskeleton, composed of microtubules and other filament types,
provides structural support and facilitates the transport of materials within the neuron. This
transport system is essential for maintaining cellular function and integrity.

Neurons are also susceptible to pathogens that may exploit their transport systems to invade
the nervous system, highlighting their vulnerability despite their specialized structures and
functions. Overall, the unique architecture of neurons enables them to effectively communicate
and process information, which is fundamental to all nervous system activities.

Implications of Glial Research

Glial research has significant implications for both understanding and treating
neurological conditions. Astrocytes, a type of glial cell, play a critical role in conditions
like HIV-associated neurocognitive disorder (HAND). When infected with the HIV virus,
astrocytes can disrupt their structural integrity, particularly their end-feet that contribute
to the formation of the blood-brain barrier. This compromise allows toxins and other
harmful substances to enter the central nervous system (CNS), increasing the risk of
further brain damage even in patients receiving effective antiretroviral therapy.
Moreover, the uncontrolled activation of microglia, another type of glial cell, is linked to
inflammation and neuronal damage in various neurodegenerative diseases, including
Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. As microglia release
inflammatory substances, their regulation becomes a critical area of focus for
developing treatment strategies aimed at mitigating neuroinflammation and protecting
neuronal health.

Research into glial cells not only enhances our understanding of these pathological
conditions but also sheds light on the healthy functioning of the nervous system. For
instance, astrocytes are involved in neurotransmitter regulation and the maintenance of
the extracellular environment, which are essential for proper neuronal signaling. Insights
gained from studying glial functions could lead to novel therapeutic approaches for
enhancing recovery from CNS injuries and improving outcomes in neurodegenerative
diseases, highlighting the dual role of glia in both supporting neuronal health and
contributing to disease processes.

Tau Protein Dynamics

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● Phosphorylation of tau protein results in its disconnection from microtubules.
● Disconnected tau protein forms tangled structures, known as neurofibrillary
tangles, which disrupt cellular signaling and structural integrity.
● The collapse of neurons due to these tangles can lead to cell death (Brandt,
2001).
Tau protein is a crucial component of the neuronal cytoskeleton, primarily involved in
stabilizing microtubules, which are essential for maintaining the structure and function of
neurons. Under normal conditions, tau binds to microtubules, helping to organize and
stabilize them, much like rungs on a ladder. However, when tau undergoes
phosphorylation—where phosphate groups are added to the protein—it becomes
detached from the microtubules. This phosphorylation is often triggered by various
enzymes and can be influenced by pathological conditions, such as neurodegenerative
diseases.

Once tau is phosphorylated and disassociates from the microtubules, it begins to

aggregate and form neurofibrillary tangles. These tangles disrupt the normal signaling
processes within the neuron and compromise its structural integrity. As a result, the
neuron may experience a collapse, leading to a loss of function and ultimately cell
death. This process is particularly significant in the context of Alzheimer's disease,
where the accumulation of neurofibrillary tangles is a hallmark feature and contributes to
the progressive decline in cognitive and physical functions associated with the disease
(Brandt, 2001).

In summary, the dynamics of tau protein are critical for neuronal health, and its
dysregulation through phosphorylation can have devastating effects on neuron structure
and function, leading to neurodegeneration.

Neuron Structure
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● Neurons possess three types of fibers in their cytoskeleton: microtubules (10 nm
in diameter), neurofilaments (middle-sized), and microfilaments (3 to 5 nm in
diameter).
● Neurofilaments provide structural support, while microfilaments are involved in
shaping neural branches during development and learning (Rajnicek, 2006).
● The neural cell body (soma) contains a nucleus, ribosomes, and organelles
necessary for protein synthesis and general cellular functions.
Neurons are specialized cells that play a crucial role in processing and transmitting
information within the nervous system. Their structure is uniquely adapted to facilitate
these functions.

1. Cytoskeleton: Neurons contain three types of fibers that make up their cytoskeleton:
- Microtubules: These are the largest fibers, approximately 25 nm in diameter, and are
responsible for the transport of materials within the neuron. They form hollow tubes that
help maintain the neuron’s shape and facilitate the movement of organelles and
vesicles.
- Neurofilaments: These are intermediate-sized fibers, typically around 10 nm in
diameter. They provide structural support to the neuron, helping to maintain its integrity
and shape, particularly in the axon.
- Microfilaments: The smallest fibers, ranging from 3 to 5 nm in diameter, are involved
in dynamic processes such as the growth and retraction of dendrites and axons during
development and in response to learning experiences (Rajnicek, 2006).

2. Neural Cell Body (Soma): The soma is the central part of the neuron and contains
essential organelles, including:
 - Nucleus: This houses the cell's DNA and is responsible for regulating cellular
activities and synthesizing proteins.
- Ribosomes: These are involved in protein synthesis, either free-floating in the
cytoplasm or associated with the rough endoplasmic reticulum.
- Organelles: Other organelles such as the Golgi apparatus and mitochondria are
present, playing roles in packaging proteins and energy production, respectively.

3. Dendrites and Axon:

- Dendrites: These are branched extensions that receive signals from other neurons.
The surface area of dendrites is critical for forming synapses and receiving
neurotransmitter signals.
- Axon: Typically a single long extension that transmits electrical impulses away from
the soma to other neurons or muscles. The axon hillock, located at the junction of the
axon and soma, is where action potentials are generated.

Overall, the structure of neurons, including their cytoskeletal fibers and organelles, is
intricately designed to support their primary functions of communication and information
processing in the nervous system.

Organelles and Their Functions

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● Ribosomes generate proteins either independently or alongside the rough
endoplasmic reticulum (RER), which appears bumpy due to ribosomes on its
surface.
● Smooth endoplasmic reticulum (SER) transports proteins to the Golgi apparatus
where they are packaged into vesicles for transport.
● Mitochondria generate ATP, the primary energy source for neurons, by
processing pyruvic acid and oxygen.

Organelles are specialized structures within cells that perform distinct functions
essential for cellular operation and maintenance. In the context of neurons, several key
organelles play critical roles:

1. Ribosomes: These are the sites of protein synthesis within the cell. Ribosomes can
function independently or be attached to the rough endoplasmic reticulum (RER). When
they are bound to the RER, they produce proteins that are either secreted from the cell
or incorporated into the cell membrane.
2. Rough Endoplasmic Reticulum (RER): The RER is characterized by its bumpy
appearance due to the presence of ribosomes on its surface. It is involved in the
synthesis of proteins, particularly those that are destined for secretion or for use in the
cell membrane. Once proteins are synthesized, they are transported to the smooth
endoplasmic reticulum.

3. Smooth Endoplasmic Reticulum (SER): The SER lacks ribosomes and is primarily
involved in the transport of proteins synthesized in the RER to the Golgi apparatus.
Additionally, it plays a role in lipid synthesis and detoxification processes.

4. Golgi Apparatus: This organelle is responsible for modifying, sorting, and packaging
proteins received from the endoplasmic reticulum into vesicles. These vesicles can then
transport the proteins to their final destinations, either inside or outside the cell.

5. Mitochondria: Known as the powerhouse of the cell, mitochondria are responsible for
producing adenosine triphosphate (ATP), the primary energy currency of the cell. They
achieve this by processing pyruvic acid and oxygen, which are derived from glucose
metabolism. The presence of many mitochondria in a neuron indicates high energy
demands, particularly in areas of the cell that require significant energy for activities
such as neurotransmitter release.

In summary, these organelles work collaboratively to ensure that neurons can

synthesize proteins, transport materials, and generate energy efficiently, which is vital
for their function in transmitting signals throughout the nervous system.

Dendrites and Axons

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● Dendrites, which resemble tree branches, receive information from other
neurons; their surface area influences the number of synapses formed.
● Dendritic spines facilitate additional synapse formation and can change shape
during learning, impacting memory (see Chapter 12).
● An axon carries messages away from the neuron; it typically has one axon and
can be significantly longer than the branches of the dendrites.
Dendrites and axons are crucial components of neurons, each serving distinct functions
in neural communication.

Dendrites:
- Dendrites are branch-like structures that extend from the neuron’s cell body,
resembling the branches of a tree. Their primary role is to receive information from other
neurons.
- The surface area of dendrites is vital because a larger surface area allows for more
synaptic connections, enhancing the neuron's ability to integrate signals from multiple
sources.
- Dendritic spines, small protrusions on dendrites, provide additional sites for synapse
formation. These spines can undergo structural changes in response to activity, which is
believed to play a significant role in learning and memory processes.

Axons:
- In contrast to dendrites, an axon is a long, slender projection that transmits electrical
impulses away from the neuron’s cell body to other neurons or target tissues. Typically,
a neuron has one axon, which can vary greatly in length, sometimes extending several
feet in larger organisms.
- The axon is responsible for carrying action potentials, which are the electrical signals
that propagate along the axon to the axon terminals. At the terminals, the signal is
converted from electrical to chemical, leading to the release of neurotransmitters into
the synaptic gap.
- Axons can also have branches known as collaterals, which allow a single axon to
communicate with multiple target cells, thereby facilitating complex signaling pathways
within the nervous system.

Together, dendrites and axons enable neurons to effectively process and transmit
information throughout the nervous system.
Action Potential and Signal Transmission
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● Action potentials, which are electrical impulses, begin at the axon hillock and
travel along the axon to the terminal where neurotransmitter release occurs.
● The diameter of axons influences the speed of signal transmission; larger axons
transmit signals faster than smaller ones.
Action potentials are rapid electrical impulses that occur in neurons, enabling them to
transmit signals over long distances. The process begins at the axon hillock, which is
the cone-shaped segment of the axon where the neuron integrates incoming signals.
When the membrane potential at the axon hillock reaches a certain threshold,
voltage-gated sodium channels open, allowing sodium ions (Na+) to flow into the
neuron. This influx of positive ions causes depolarization, reversing the membrane
potential and creating the action potential.

Once initiated, the action potential propagates down the length of the axon. The speed
of this transmission is significantly influenced by the axon's diameter; larger diameter
axons allow for faster signal conduction due to reduced resistance to ion flow.
Additionally, many vertebrate axons are insulated by myelin, a fatty substance that
wraps around the axon in segments. This myelination increases the speed of signal
transmission through a process called saltatory conduction, where the action potential
jumps from one node of Ranvier (unmyelinated section) to the next, further enhancing
efficiency.

When the action potential reaches the axon terminal, it triggers the release of
neurotransmitters from synaptic vesicles into the synaptic gap. These neurotransmitters
then bind to receptors on the postsynaptic neuron, facilitating communication between
neurons and continuing the signaling process. Thus, action potentials are essential for
the rapid and efficient transmission of information within the nervous system.

Myelin and Ion Channels

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● Myelin is an insulating layer surrounding some axons, allowing for faster signal
transmission; it does not cover the entire axon length.
● Nodes of Ranvier are gaps between myelin segments that are critical for the
movement of action potentials.
● Myelin reduces the energy requirements by limiting the number of ion channels
needed along the axon.
Myelin is a fatty insulating layer that surrounds certain axons in the nervous system,
significantly enhancing the speed and efficiency of electrical signal transmission. This
insulation allows for smaller diameter axons to maintain high conduction velocities,
which is crucial for efficient neural communication. However, myelin does not cover the
entire length of an axon; it is segmented, with gaps known as Nodes of Ranvier
occurring between myelin segments. These nodes are critical for the propagation of
action potentials, as they contain a high density of ion channels that facilitate the rapid
influx and efflux of ions, thereby enabling the electrical signal to "jump" from node to
node in a process called saltatory conduction.

The presence of myelin also reduces the energy requirements of neurons. In myelinated
axons, fewer ion channels are needed along the axon membrane, as the myelin sheath
prevents ion movement in the insulated regions. Consequently, the sodium-potassium
pumps, which are responsible for restoring ion concentrations after action potentials, do
less work in myelinated axons compared to unmyelinated ones. This energy efficiency
is vital for the overall metabolic demands of the nervous system, allowing for greater
information processing and communication without excessive energy expenditure.

Neuron Classification
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● Neurons are categorized by structural and functional characteristics, including
unipolar, bipolar, and multipolar types.
● Unipolar neurons have a single branch and are found in sensory systems while
bipolar neurons, which have one axon and one dendrite, are common in sensory
pathways like the retina.
● The most prevalent type, multipolar neurons typically have numerous dendrites
and a single axon; these include motor and interneurons, facilitating
communication within nervous systems.
Neurons can be classified based on their structural and functional characteristics, which
reflect their roles in the nervous system. The primary types of neurons include unipolar,
bipolar, and multipolar neurons.

1. Unipolar Neurons: These neurons have a single branch that extends from the cell
body and then splits into two. They are primarily found in the sensory systems of
vertebrates, where they play a crucial role in transmitting sensory information from the
periphery (such as skin and muscles) back to the central nervous system (CNS).
Unipolar neurons are important for encoding and transmitting information related to
touch, temperature, and pain.
2. Bipolar Neurons: Bipolar neurons possess two branches extending from the cell
body: one axon and one dendrite. They are commonly found in sensory pathways,
particularly in the retina of the eye, where they are involved in the processing of visual
information. Their structure allows them to efficiently relay signals between sensory
receptors and other neurons.

3. Multipolar Neurons: The most common type of neuron in the vertebrate nervous
system, multipolar neurons have multiple dendrites and a single axon. This structure
allows them to integrate a vast amount of information from various sources. Multipolar
neurons can be further classified into two categories:
- Motor Neurons: These neurons transmit commands from the CNS to muscles and
glands, facilitating movement and physiological responses.
- Interneurons: These neurons act as bridges between sensory and motor neurons,
processing information locally and playing a critical role in reflexes and complex neural
circuits.

Overall, the classification of neurons into unipolar, bipolar, and multipolar types is
essential for understanding their specific functions in sensory processing, motor control,
and interneuronal communication within the nervous system.

Ionic Composition and Resting Potential

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● The intracellular and extracellular fluids differ significantly in ion concentrations,
affecting neuronal electrical signaling.
● The resting potential of a neuron is about −70 mV, indicating a more negative
internal environment compared to the external one.
● This potential is maintained by sodium-potassium pumps that help to keep ion
concentrations balanced across the neural membrane.
The ionic composition of intracellular and extracellular fluids is crucial for neuronal
function and electrical signaling. Intracellular fluid, which is the fluid inside the neuron,
has a high concentration of potassium ions (K+) and relatively few sodium (Na+) and
chloride (Cl−) ions. In contrast, extracellular fluid, the fluid surrounding the neuron, is
characterized by high concentrations of sodium and chloride ions, with lower levels of
potassium. This difference in ion concentration creates a gradient that is essential for
generating electrical signals.
The resting potential of a neuron is approximately −70 millivolts (mV), indicating that the
interior of the neuron is more negatively charged compared to the outside. This resting
potential is a result of the unequal distribution of ions across the neuronal membrane,
primarily maintained by sodium-potassium pumps. These pumps actively transport three
sodium ions out of the neuron while bringing two potassium ions in, using energy in the
form of ATP. This activity not only helps maintain the resting potential but also ensures
that the neuron is ready to fire an action potential when stimulated.

Overall, the ionic composition and resting potential are fundamental to the neuron's
ability to transmit signals, as they create the necessary conditions for action potentials
to occur when the neuron is activated.