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Module I:EXELON® PATCH

Anatomy and Physiology ofthe Nervous System

EXELON® PATCH Learning System

Module I: EXELON® PATCH Anatomy and Physiology of the Nervous System

This information is for internal use only and is not to be left with, detailed from, or shown to anyone

outside of Novartis Pharmaceuticals Corporation.

Welcome ............................................................................................................... 4

Program Overview .......................................................................................... 4

What to Expect .............................................................................................. 5

Anatomy of the Nervous System ........................................................................... 6

Chapter Learning Objectives ............................................................................ 6

Organization of the Nervous System ................................................................. 7

Introduction ........................................................................................ 7

Divisions ............................................................................................. 7

Peripheral Nervous System ................................................................... 8

Recall Exercise .............................................................................................. 10

Cells of the Nervous System .......................................................................... 11

Introduction ....................................................................................... 11

Anatomy of the Neuron ....................................................................... 11

Functional Classification of Neurons ....................................................... 13

Recall Exercise .............................................................................................. 14

The Central Nervous System: The Brain .......................................................... 15

Overview ........................................................................................... 15

The Cerebral Hemispheres .................................................................... 16

The Cerebral Cortex ............................................................................. 16

Anatomy and Function of the Structures of the Cerebral Hemispheres ......... 18

Recall Exercise .............................................................................................. 19

The Diencephalon ............................................................................... 20

The Brain Stem .................................................................................. 21

The Cerebellum .................................................................................. 22

Summary of Diencephalon, Brain Stem, and Cerebellum Anatomy and Functions .................................................................................... 23

Overview of the Limbic System ............................................................ 24

Structures of the Limbic System ........................................................... 25

Table of Contents




The Central Nervous System: The Spinal Cord .................................................. 26

Recall Exercise .............................................................................................. 27

The Central Nervous System: The Spinal Cord ................................................... 28

Recall Exercise ............................................................................................. 31

Chapter Summary ........................................................................................ 32

Self-check .................................................................................................... 34

Physiology of the Nervous System ..................................................................... 36

Chapter Learning Objectives ........................................................................... 36

Neurotransmission ........................................................................................ 37

Introduction ....................................................................................... 37

Process of Neurotransmission ................................................................ 37

Stages ............................................................................................... 42

Recall Exercise .............................................................................................. 44

Chemical Classification ......................................................................... 45

Functional Classification ....................................................................... 46

Recall Exercise ............................................................................................. 47

Acetylcholine and Its Role in Neurotransmission ................................................ 48

Importance ........................................................................................ 48

Synthesis ........................................................................................... 48

Receptors ........................................................................................... 49

Degradation ....................................................................................... 49

Glutamate and Its Role in Learning and Memory ................................................ 50

Recall Exercise .............................................................................................. 51

Chapter Summary ......................................................................................... 52

Self-check .................................................................................................... 54

Glossary .............................................................................................................. 56




Welcome Welcome to Module I: Anatomy and Physiology of the Nervous System in the EXELON® PATCH Learning System. This module consists of two chapters:

Anatomy of the Nervous System: Provides an overview of the nervous system and its components

Physiology of the Nervous System: Details the dynamics of how the nervous system works and the various chemicals involved in the transmission of nervous impulses.

Recall exercises are located throughout each chapter to test your understanding of the material. In addition, you will find a series of multiple-choice quiz questions at the end of each chapter to help reinforce what you have learned.

Program Overview Alzheimer disease (AD) is a gradually progressing and fatal neurodegenerative

disorder manifested by cognitive and memory deterioration, progressive impairment of activities of daily living, and a variety of neuropsychiatric symptoms and behavior disturbances. According to the current statistics (2011) of Alzheimer Association, approximately 5.4 million individuals in the United States have AD; 5.2 million people 65 years of age and older have the disease.

Parkinson’s disease (PD) is the most common form of progressive neurodegenerative

movement disorders characterized by clinical features such as tremor, rigidity, bradykinesia, and postural instability. PD affects about 1 million people in the United States (about 1% of those over 55 years of age). The incidence of dementia in patients with PD is six times higher than the non-PD population

EXELON PATCH (rivastigmine transdermal system) is a reversible cholinesterase

inhibitor approved for the treatment of mild to moderate dementia of the Alzheimer type and mild to moderate dementia associated with PD. It has demonstrated efficacy and provides significant benefit in cognition and overall functioning.




What to Expect This module will review background information on the anatomy and physiology of the nervous system, which is central to understanding the pathophysiology and treatment of AD and Parkinson disease dementia (PDD).

The purpose of this module is to prepare you for selling EXELON PATCH by teaching you about the structure and function of the nervous system,

providing a foundation for understanding the changes that occur to cause dementia and how EXELON PATCH works.




Anatomy of the Nervous System

Chapter Learning Objectives After completing this chapter, you should be able to:

1. Describe the primary functions and the 2 main divisions of the nervous system

2. Identify the subdivisions of the peripheral nervous system (PNS) and how they operate

3. Identify the parts of a neuron, the functional classification of neurons, and the cells that support and protect neurons

4. List the higher- and lower-level functions of the brain and describe the structures and functions of the cerebral hemispheres, cerebral cortex, diencephalon, brain stem, cerebellum, and limbic system

5. Describe the spinal cord and its function

6. Identify the structures that comprise the PNS and describe their functions




Organization of the Nervous System

Introduction

The nervous system is a complex network that controls every thought, emotion, and action of the body by means of electrical and chemical signals. Three of its primary functions include:

1. Monitoring internal and external stimuli

2. Processing and interpreting input

3. Activating muscles, organs, and glands

To understand how these functions are performed, it is helpful to think of the nervous system as having a number of divisions that work seamlessly together.

Divisions There are 2 main divisions of the nervous system:

The central nervous system (CNS) is the body's command center and consists of the brain and spinal cord.

The PNS connects the CNS to the rest

of the body.




Peripheral Nervous System Overview The PNS can be further divided into 2 subdivisions that communicate with the CNS:

The afferent (sensory) division delivers information through afferent nerve

fibers to the CNS from sensors located throughout the body in muscles, skin, and joints.

The efferent (motor) division carries signals from the CNS through efferent

nerve fibers to muscles, activating a motor response.

For example, when you are driving and see a red light ahead, the afferent fiber sends a sensory signal to the CNS that you need to stop, and the CNS

sends a signal through the efferent fibers to the muscles in your foot in order to step on the brake.

Efferent Division The efferent division also has 2 subdivisions:

The somatic nervous system

controls voluntary skeletal muscle actions that require a conscious effort.

The autonomic nervous system

controls involuntary or "automatic" muscle actions that do not require a conscious effort and controls the body's everyday needs, such as digestion and heart rate.




Autonomic Nervous System The autonomic nervous system also has 2 subdivisions:

The sympathetic nervous system is responsible for mobilizing body systems

when the body requires activity (known as the "fight or flight" response).

The parasympathetic nervous system is responsible for conserving energy and maintaining organ function during periods of minimal physical activity, such as rest and digestion.

Together, the sympathetic and parasympathetic nervous systems stimulate and inhibit the visceral (internal) organs.




Recall Exercise Complete the statements below using the following terms:

Somatic Afferent Central Peripheral Parasympathetic

1. The _________________ nervous system is responsible for conserving energy and maintaining organ function during periods of minimal activity, such as rest and digestion.

2. The _________________ division of the PNS delivers information to the CNS from sensors located throughout the body.

3. The _________________ nervous system is the body’s command center and consists of the brain and spinal cord.

4. The _________________ nervous system controls voluntary skeletal muscle actions, such as chewing or walking.

5. The _________________ nervous system connects the CNS to the rest of the body.

ANSWERS: 1. Parasympathetic, 2. Afferent, 3. Central, 4. Somatic, 5. Peripheral




Cells of the Nervous System

Introduction The nervous system comprises 2 types of nervous tissue:

1. Neurons are the highly specialized cells that conduct signals throughout the body.

Neurons are usually large, complex cells that vary in structure.

All neurons have several distinct similarities in anatomy.

2. Glial cells (or neuroglia) support neurons and promote their growth and health.

Because neurons are important, delicate cells that transmit electrical and chemical signals, they depend on glial cells for support.

Glial cells protect and nourish the neurons. There are many more glial cells

than neurons.

Glial cells are so important that there are about 6 different types, including those that engulf and destroy microorganisms as well as those that help insulate nerve fibers or circulate cerebrospinal fluid.

o Four types are found in the CNS: astrocytes, microglia, ependymal cells, and oligodendrocytes.

o Two types are found in the PNS: satellite cells and Schwann cells.

Anatomy of the Neuron Overview

All neurons have a soma (cell body)

that contains the nucleus as well as other structures important for maintaining cell life, including cytoplasm, organelles, ribosomes, and endoplasmic reticulum.

Emanating from the neuronal soma

are 2 types of processes or extensions:

o Dendrites o Axons




Dendrites Dendrites are branching processes

that make it possible for neurons to communicate with other neurons.

Dendrites provide a large surface

area with which to receive signals from other neurons. They direct the signals into the neuron cell body, where they are forwarded to the axon.

Axons

Axons are long, cylindrical projections that deliver signals to other neurons or to a

target muscle or organ. Nearly all neurons have 1 axon, which can range in length from very short to up to 4 feet.

They are the functional conducting component of the neuron because they generate and then transmit nerve impulses. The impulse travels along the axon to the end, where it may divide into as many as 10,000 branches or telodendria. This is where the axon terminals reside and neurotransmission takes place.

Axons of long and large-diameter neurons are usually covered in a white coating called a myelin sheath, which serves to protect the axon from damage and also acts as insulation—greatly increasing the speed of impulse transmission.

In the PNS, myelin sheaths appear segmented with gaps and are formed by Schwann cells. In the CNS, myelin sheaths do not appear to be segmented and are formed by oligodendrocytes

Myelinated and nonmyelinated axons can be found in both the PNS and CNS.




Functional Classification of Neurons Neurons can be functionally

described by the direction in which they carry signals.

There are 3 functional types of

neurons: 1. Sensory (afferent) neurons

carry signals from the PNS to the CNS.

2. Motor (efferent) neurons carry signals from the CNS to the PNS.

3. Association neurons (interneurons) carry signals between sensory and motor neurons. They comprise more than 99% of all neurons in the body, and most are located entirely within the CNS.




Recall Exercise Complete the statements below using one of the following terms:

Axons Dendrites Sensory Motor Association

1. _________________ Generate and transmit nerve impulses

2. _________________ Neurons that carry signals from the PNS to the CNS

3. _________________ Neurons that carry signals between sensory and motor neurons

4. _________________ Direct the signals into the neuron cell body, where they are forwarded to the axon

5. _________________ Can range in length from very short to up to 4 feet

6. _________________ Neurons that carry signals from the CNS to the PNS

7. _________________ Branching processes that provide a large surface area with which to receive signals from other neurons

8. _________________ Comprise more than 99% of all neurons in the body

ANSWERS: 1. Axons, 2. Sensory, 3. Association, 4. Dendrites, 5. Axons, 6. Motor, 7. Dendrites, 8. Association




The Central Nervous System: The Brain

Overview The CNS—the brain and spinal

cord—comprises a complex messaging system.

The brain regulates the activity of

the nervous system.

It is made up of several divisions, each with its own anatomy and function. These divisions control higher-level brain functions, or "the mind" (consciousness, memory, reasoning, and language), as well as lower-level, involuntary brain functions (heart rate, body temperature, and digestion).

The brain consists of the following

parts: o Cerebral hemispheres o Diencephalon o Brain stem o Cerebellum o Limbic system




The Cerebral Hemispheres The cerebral hemispheres form the superior part of the brain and account for

about 83% of the total brain mass.

Nearly the entire surface of the cerebral hemispheres is marked by elevated ridges of tissue called gyri, separated by shallow grooves called sulci.

The Cerebral Cortex The cerebral cortex is the thin

(1/8" thick) outer layer of the cerebral hemispheres. Because of its convoluted surface of gyri and sulci, which triple the surface area of the cortex and give the brain its distinctive outer appearance, the cortex accounts for almost half of the mass of the brain.

The cortex consists entirely of

gray matter, which appears gray in color because the neurons are nonmyelinated. Metabolic activity and blood flow in various regions of the cerebral hemispheres enable conscious behavior.

The cerebral cortex comprises

3 distinct functional areas that correspond to specific brain functions: motor areas, sensory areas, and association areas.

1

3 2




1. Sensory Areas

Sensory areas enable conscious awareness of sensations such as touch, taste, and

hearing. They are spread out over a larger area of the cerebral hemispheres, including the

parietal, temporal, and occipital lobes. The sensitivity of an area of the body is a reflection of the amount of sensory

receptors devoted to that specific area. For example, fingertips are very sensitive and therefore have many sensory receptors.

2. Association Areas

Association areas are connected to, but work independently of, the motor and

sensory areas to integrate information into purposeful action.

The most complex association area is in the anterior part of the frontal lobe.

This area is involved in intellect, complex learning, personality, and emotion and is closely linked with the emotional part of the brain known as the limbic system, which will be discussed later in this chapter.

3. Motor Areas Motor areas control voluntary motor functions such as leg, arm, and eye

movement. They lie in the posterior part of the frontal lobes of the cerebral hemispheres.




Anatomy and Function of the Structures of the Cerebral Hemispheres This table provides a summary of the cerebral hemispheres' anatomy and function.

Lobes of the Central Hemispheres Functional Areas Function

Frontal Lobe

Motor Controls voluntary motor functions

Association Integrates information into purposeful action

Parietal, Insular, Temporal, and Occipital Lobes

Sensory Enables conscious awareness of sensations




Recall Exercise

1. __________ Which of the following is a higher-level brain function? A. Heart rate B. Body temperature C. Memory D. Digestion

2. __________ The cerebral hemispheres comprise the largest and most superior part of

the brain and account for about 50% of the total brain mass. A. True B. False

3. The cerebral cortex accounts for almost __________ of the mass of the cerebral hemispheres. A. 1/3 B. 1/2 C. 2/3 D. 3/4

4. __________ Motor areas of the cerebral cortex control voluntary motor functions such as leg, arm, and eye movement. A. True B. False

5. __________ The cortex consists entirely of white matter, which appears white in color

because the neurons are myelinated. A. True B. False

6. __________ Which of the following lobes are associated with the motor areas and the

most complex association area?

A. Occipital lobe B. Parietal lobe C. Insular lobe D. Frontal lobe

ANSWERS: 1. C, 2. B, 3. B, 4. A, 5. B, 6. D




The Diencephalon The diencephalon is located

deep within the frontal lobe of the brain, surrounded by the cerebral hemispheres.

The diencephalon comprises 3

structures: o Thalamus o Hypothalamus o Epithalamus o

1. Thalamus The thalamus is the largest of these structures, representing about 80% of the

diencephalon.

It acts as the brain's relay station, receiving afferent (incoming) signals from all parts of the body and relaying those signals to specific regions of the cerebral cortex for processing, including:

o Sensory inputs o Emotional inputs o Visceral inputs o Motor inputs

The thalamus also edits the input it receives, recognizing and grouping similar

signals before sending them onto the appropriate sensory or association areas.

As a result, the thalamus is involved in sensation, motor activity, stimulation of the cerebral cortex, learning, and memory.

2

1

3




2. Hypothalamus

The hypothalamus is located below the thalamus (hypo = below). Although small

in size, it is charged with the huge responsibility of maintaining the body's homeostasis.

The hypothalamus controls the entire autonomic nervous system and can affect

everything from the rate and force of heart contraction to respiration to digestive tract motility and even eye pupil size.

The hypothalamus also serves as the center for emotional response and behavior.

It is involved in the following functions: o Perceptions of pleasure, fear, and rage o Control of biological functions such as circadian rhythm, sex drive, and

hormones o Regulation of body temperature, water balance, thirst, and hunger

3. Epithalamus

The epithalamus is located posterior to the thalamus (epi = following or upon) and

is the most dorsal portion of the diencephalons.

It includes the hormone-secreting pineal gland that, in conjunction with the hypothalamus, regulates circadian rhythm.

The Brain Stem Another part of the brain that

is integrally involved in rigidly programmed behaviors or lower-level brain function is the brain stem.

The brain stem is located at the

bottom of the brain, just above the spinal cord, and comprises 3 regions:

o Midbrain o Pons o Medulla oblongata

Collectively, the brain stem

coordinates essential motor reflexes necessary for survival, including the functioning of the cardiovascular and respiratory systems.

2

1

3




1. Midbrain

The midbrain is the most superior part of the brain stem, and affects the control of muscles and glands.

2. Pons The pons is the distinctive bulging area of the brain stem between the midbrain and

medulla oblongata.

It works with the medulla oblongata to maintain normal breathing rhythm and acts as a relay between the motor areas of the cerebral cortex and the cerebellum.

3. Medulla Oblongata

The medulla oblongata is the most inferior aspect of the brain stem and is responsible for carrying out instructions from the hypothalamus to control the body's most vital motor functions of circulation and respiration, as well as other activities such as swallowing, vomiting, hiccupping, coughing, and sneezing.

The Cerebellum The cerebellum is involved in

lower-level functioning or subconscious motor functions. It is the second-largest part of the brain, accounting for about 11% of total brain mass.

The cerebellum is responsible for

providing precise timing and appropriate patterns of skeletal muscle contraction for smooth, coordinated movement.

It is believed that the cerebellum

may also play a significant role in learning and memory.




Summary of Diencephalon, Brain Stem, and Cerebellum Anatomy and Functions This table provides a summary of diencephalon, brain stem, and cerebellum anatomy and functions.

Anatomical Structures Substructures Function

Diencephalon

Thalamus Relays afferent signals to specific regions of the cerebral cortex

Hypothalamus Controls the autonomic nervous system; also the center for emotional response and behavior

Epithalamus Regulates circadian rhythm

Brain Stem Midbrain Affects the control of muscles and glands

Pons Maintains breathing, relays signals between the cerebral cortex and the cerebellum

Medulla Oblongata Works with hypothalamus to control the body’s most vital motor functions

Cerebellum None Maintains skeletal muscle contraction for smooth, coordinated movement; may also affect learning and memory




Overview of the Limbic System The limbic system is a group of regions within the brain that are integrally involved

in emotion and memory. It is located at the center of the cerebral hemispheres and encircles part of the brain stem.

The limbic system is extensively connected to the rest of the brain, enabling it to

integrate and respond to a variety of environmental stimuli.

Through its connections to the hypothalamus, from which autonomic and emotional responses emanate, the limbic system is able to link emotions to visceral responses such as heartburn and high blood pressure. It is by this process that emotion-induced illnesses, or psychosomatic illnesses, can occur.

By interacting with the prefrontal lobes, the limbic system is also able to form

intimate relationships between feelings and thoughts. This intercommunication enables emotions to sometimes override logic, and logic to censor inappropriate emotional response.

Alzheimer Link

AD affects neurons in the cerebral cortex and the limbic system, eventually

destroying their structure and impacting function.

It is not surprising that patients with AD exhibit memory loss, shortened attention span, disorientation and language loss that gets worse over time.



outside of Novartis Pharmaceuticals Corporation. Ch-1, S-3,

Structures of the Limbic System The major structures of the limbic

system are the: o Hippocampus: Incorporates

and stores sensory signals into memory and controls neurons affecting spatial memory tasks, sequential spatial locations, and temporal memory order of nonspatial locations

o Amygdala: Incorporates and stores sensory signals into memory and associates memories formed through the senses with emotional states

As previously mentioned, the limbic system is integrally involved in memory. The hippocampus and amygdala incorporate and store sensory signals that become memories. This is where recent information such as fearful faces are stored.

Other regions of the brain involved with memory include the association areas of the cerebral cortex, which processes information from primary cortical sensory regions to produce higher cortical functions such as memory, and the thalamus.




The Central Nervous System: The Spinal Cord The spinal cord is a nerve

superhighway upon which afferent (incoming) sensory signals and efferent (outgoing) motor signals are relayed between lower- and higher-functioning organ systems.

The cord is about 17" long and ¾"

thick, and runs from the base of the brain stem to just below the level of the ribs, ending at the first or second of the lumbar vertebrae. It is enclosed and protected by surrounding bone called the vertebral column.

The spinal cord consists of an

innermost layer of gray matter, white matter, and a sheath of strong dura material. There are a total of 31 pairs of spinal nerves that project from the spinal cord toward the body areas they serve.

The epidural space between the vertebrae and the spinal dura material contains a

cushion of protective fat and a network of veins. Cerebrospinal fluid fills the spaces within the spinal cord.




Recall Exercise Match each term on the right with its corresponding statement on the left

1. _____ Controls the entire autonomic nervous system and can affect everything from the rate and force of heart contraction to digestive tract motility and even eye pupil size

A. Cerebellum

2. _____ Enables the brain to form intimate relationships between emotions and visceral responses

B. Hypothalamus

3. _____ Maintains skeletal muscle contraction for smooth, coordinated movement; may also affect learning and memory

C. Spinal cord

4. _____ Coordinates essential motor reflexes necessary for survival, including the functioning of the cardiovascular and respiratory systems

D. Limbic system

5. _____ Nerve superhighway upon which afferent (incoming) sensory signals and efferent (outgoing) motor signals are relayed between lower- and higher-functioning organ systems

E. Brain stem

ANSWERS: 1. B, 2. D, 3. A, 4. E, 5. C, 6. C




The Central Nervous System: The Spinal Cord Structures

The PNS is the part of the nervous system where sensory signals originate and

motor signals exert their effect. It comprises all neural structures that are not a part of the CNS.

The structures of the PNS include:

o Sensory receptors o Peripheral nerves o Ganglia o Motor endings

Sensory Receptors Sensory receptors are specialized neurons that respond to environmental changes

called stimuli.

Such stimuli cause a chain reaction of electrical changes within the neuron that, in turn, trigger other neurons, sending an afferent signal into the spinal cord and to the brain, where the signals are processed.

Peripheral Nerves

Peripheral nerves are cord-like organs comprising multiple peripheral axons from

multiple neurons.

Peripheral nerves are classified by the direction in which they transmit signals to and from the CNS.

There are 3 types of nerves in the PNS: o Sensory nerves: afferent nerves that carry signals to the CNS o Motor nerves: efferent nerves that deliver signals away from the CNS o Mixed nerves: nerves that transmit signals both to and from the CNS and

are the majority of nerves in the body

Nerves can also be classified according to whether they emanate from the brain (cranial nerves) or the spinal cord (spinal nerves).




Ganglia

While the axons of neurons in the PNS are contained in nerves as just described, the neuron cell bodies (somas) are contained in ganglia.

Motor Endings

Motor endings are a part of the

PNS where signals from the brain activate effector responses by the release of neurotransmitters, a process that will be described in Chapter 2.

In the skeletal nerves, or

somatic nerves, the release of neurotransmitter occurs at axon terminals, where the axon branches out as it reaches its target skeletal muscle. The neuromuscular junction where the axon terminal and target muscle meet is called the synaptic cleft.




Motor Endings (continued)

Chemical versus Electrical Synaptic Pathways The speed of a motor response induced by a nerve is determined by the amount

of the chemical synaptic pathways involved versus the faster electrical synaptic pathways.

Visceral motor responses tend to be slower than those induced by somatic motor fibers, which directly open ion channels (use electrical synaptic pathways).




Recall Exercise Label each statement as TRUE or FALSE.

1. ________ Specialized neurons in the peripheral nervous system that respond to stimuli are referred to as sensory receptors.

2. ________ Most peripheral nerves are sensory nerves.

3. ________ Both axons and neuronal cell bodies are found in ganglia.

4. ________ Peripheral nerves are classified by the direction in which they transmit signals to and from the CNS.

5. ________ Motor endings are a part of the afferent division of the PNS.

ANSWERS: 1. True, 2. False, 3. False, 4. True, 5. False




Chapter Summary The nervous system functions to monitor internal and external stimuli; process and

interpret input; and activate muscles, organs, and glands for appropriate response.

The nervous system is divided into subdivisions based on function: o The CNS is the body's command center and consists of the brain and

spinal cord. o The PNS connects the rest of the body to the CNS. o The afferent division delivers signals to the CNS from sensors located

throughout the body in muscles, skin, and joints. o The efferent division delivers signals from the CNS through efferent nerve

fibers to muscles. o The somatic nervous system controls voluntary skeletal muscle action. o The autonomic nervous system controls involuntary muscle action. o The sympathetic and parasympathetic nervous systems stimulate and

inhibit visceral organs. Neurons are the primary, but not the most abundant, cells in the nervous system.

The anatomical structures of neurons include the soma (cell body), dendrites, and

axons.

There are 6 types of glial cells, or supporting cells, that protect neurons.

Higher-level brain functions include consciousness, memory, reasoning, and language.

The cerebral hemispheres (also known as the cerebral cortex) are divided into

frontal, parietal, temporal, occipital lobes and insular lobes

Functional areas of the cerebral hemispheres include motor, sensory, and association areas.

The functions of the diencephalon, brain stem, and cerebellum include:

o Relaying afferent signals to specific regions of the cerebral cortex o Coordinating essential motor reflexes necessary for survival o Being involved in emotions and memory

The limbic system is integrally involved in emotion and memory.

o Primary structures of the limbic system are the hippocampus and the amygdala.

o These structures incorporate and store sensory signals in an area of the brain’s memory centers reserved for remembering facts.

The spinal cord conducts the flow of afferent (incoming) and efferent (outgoing)

signals between lower- and higher-functioning organ systems.




Sensory receptors are specialized neurons that respond to stimuli and begin the chain reaction of signal transmission to the brain.

Most nerves in the PNS are mixed nerves that transmit signals both to and from

the CNS.

Signals from the brain are converted to motor responses by the release of neurotransmitters at neuromuscular junctions.




Self-check

1. Which of the following comprise more than 99% of all neurons in the body? A. Sensory (afferent) neurons B. Motor (efferent) neurons C. Association neurons (interneurons) D. Presynaptic neurons

2. Which structure is NOT a part of the brain stem?

A. Chewing B. Digestion C. Heart rate D. Spinal cord

3. Which of the following comprise more than 99% of all neurons in the body?

A. Sensory (afferent) neurons B. Motor (efferent) neurons C. Association neurons (interneurons) D. Presynaptic neurons

4. Which structure is NOT a part of the brain stem?

A. Hippocampus B. Midbrain C. Pons D. Medulla oblongata

5. The spinal cord comprises an innermost layer of gray matter, white matter, and a

sheath of strong _____________ material. A. Dura B. Myelin C. Fat D. Medulla oblongata




6. In the skeletal nerves, or somatic nerves, the release of neurotransmitter occurs at _____________ where the axon branches out as it reaches its target skeletal muscle.

A. Dendrites B. Telodendria C. Axon terminals D. Axons

ANSWERS: 1. A, 2. D, 3. C, 4. A, 5. A, 6. C




Physiology of the Nervous System

Chapter Learning Objectives After completing this chapter, you should be able to:

1. Describe the 5 stages that occur in the process of neurotransmission and list the neuronal structures involved

2. Describe how the resting membrane potential is transformed into action potential

3. Discuss the 4 events that occur during the neurotransmission stage and identify the 3 mechanisms by which the effect of a neurotransmitter can be terminated

4. List the 5 chemical classes of neurotransmitters and describe how they are classified according to their functions

5. Describe the significance of acetylcholine (ACh) and ACh receptors and discuss ACh synthesis and degradation

6. Discuss the role of glutamate in learning and memory and identify the 2 main glutamate receptors




Neurotransmission

Introduction

Neurons transmit signals to and from the body and CNS via a combination of electrical and chemical impulses that travel between cells in a process called neurotransmission.

When a neuron is on the "sending"

side of the synapse, it is referred to as a presynaptic neuron. When it is on the "receiving" side, it is referred to as a postsynaptic neuron. Neurons can function as both presynaptic and postsynaptic neurons.

Process of Neurotransmission Overview The process of neurotransmission, which is the chain of events that occurs to transfer information across a neural synapse, occurs in 5 stages: Stage 1: Sensory stimulation

Stage 2: Ion flow

Stage 3: Depolarization/repolarization

Stage 4: Neurotransmission

Stage 5: Signal termination




Overview (continued)

Neurotransmission Neurons can transmit impulses only when they are adequately stimulated, which

means they must reach a certain threshold point.

Strong stimuli cause nerve impulses to be generated more often in a given time interval than do weak stimuli, so the intensity of a stimulus is coded by the frequency, not strength, of action potentials.

The stronger the stimuli, the greater the frequency of action potentials and an

increase in frequency of neurotransmitter release.

Stage 1: Sensory Stimulation Neurotransmission begins with the arrival of an action potential at the presynaptic

axon terminal.

The impulse is transmitted into the cell body. When the impulse reaches the axon terminals, it sets off a complex chain of chemical reactions within the neuron.

Stage 2: Ion Flow Plasma membranes have a variety of membrane proteins that act as ion channels

and permit the flow of electrically charged ions (notably sodium and potassium) into and out of cells.

Normally, the electrical charge inside the neuron is negatively charged relative to

the charge outside of the neuron. This difference in a resting neuron is called the resting membrane potential, and the membrane is said to be polarized.

Stage 3: Depolarization/Repolarization Neurons transmit signals to other neurons and target cells by briefly reversing the electrical charge normally present along the axon membrane. In this manner, the resting membrane potential is transformed into action potential. This occurs in the axon through a process of depolarization, which makes the membrane potential less negative, and repolarization, which returns the membrane potential to rest. This action is similar to a wave carrying the sensory impulse down the axon.




Stage 3: Depolarization/Repolarization (continued) Depolarization/Repolarization

During depolarization:

o Sodium ion channels open, allowing positively charged sodium to rush into the cell, causing rapid depolarization and an increase in action potential.

o The resulting change to a positive charge causes the sodium ion channels to close.

During repolarization: o Potassium ion channels open, allowing positively charged potassium to

rush out of the cell. o The cell's internal negativity is restored and the neuron is at rest.




Stage 4: Neurotransmission Neurotransmission itself involves 4 steps:

1. When the wave of membrane depolarization reaches the axon terminal, it opens

calcium and sodium ion channels, allowing calcium and sodium to rush in.

2. The influx of calcium triggers the synaptic vesicles or neurotransmitter-containing vesicles to release their contents into the synaptic cleft by a process called exocytosis.

3. The neurotransmitter travels across the synaptic cleft and binds to receptors on the postsynaptic membrane, delivering the impulse to the next neuron or target cell.

4. Ion channels on the postsynaptic membrane open, allowing the signal to be delivered.

Neurotransmission




Stage 5: Signal Termination Once bound, neurotransmitters continue to affect postsynaptic receptors, effectively blocking them from receiving other signals. Therefore, their effect must be terminated once the impulse is delivered. This is achieved by 3 different mechanisms: Degradation of the neurotransmitter by enzymes

Reuptake of the neurotransmitter into the presynaptic axon terminal

Diffusion of the neurotransmitter away from the synapse

Medications Various medications can affect neurotransmission by: Modifying the amount of neurotransmitter released

Blocking receptors for neurotransmitters

Affecting the elimination of neurotransmitters

Blocking reuptake of neurotransmitters




Stages The following images illustrate the Stages of Neurotransmission.

Neurotransmission is the process by which neurons receive and transmit signals through the CNS and PNS. Stage 1: Sensory Stimulation Neurotransmission begins when the dendrites of a neuron are stimulated by an external source or by another neuron. The impulse is transmitted to the soma, setting off a complex chain of chemical reactions that takes place in stage 2. Stage 2: Ion Flow When at rest, the inside of a neuron has a slight negative electrical charge in comparison to the external environment. In addition, there is a higher concentration of positively charged sodium ions outside of a neuron while a higher concentration of positively charged potassium ions is found inside a neuron. Sodium and the potassium channels and the sodium/potassium pump located within the neuron cell membrane help control the homeostasis of the neuron and the resting potential of the cell membrane. During the second stage of neurotransmission, there is a brief opening of sodium channels in the membrane allowing the positively charged sodium ions to enter the cell. This is immediately followed by the opening of potassium channels which allow the positively charged

potassium ions to flow out of the cell restoring the negative resting membrane potential. In the recovery phase, the active sodium/potassium pump on the cell membrane restores the sodium and potassium ions to their normal pre-action potential levels by pumping sodium to the outside of the cell and pumping potassium to the inside of the cell.




Stages (continued) Stage 3: Depolarization/Repolarization Neurons transmit signals through the length of the neuron by opening and closing sodium and potassium channels along the neuron, moving the positively charged sodium and potassium in and out of the cell and briefly reversing the electrical charge normally present along the axon membrane. This process of brief depolarization and repolarization acts as a wave carrying the signal down the axon. Stage 4: Neurotransmission The fourth stage, neurotransmission, involves four steps: Step 1: In Step 1, when the wave of membrane depolarization reaches the axon terminal, it opens calcium channels allowing calcium to rush in. Step 2: In Step 2, the influx of calcium triggers the synaptic

vesicles to release neurotransmitters such as, dopamine, norepinephrine, serotonin and ACh into the synaptic cleft. ACh is an important neurotransmitter found in the central, peripheral, somatic, autonomic, and parasympathetic nervous systems. It stimulates all skeletal muscles and viscera. It is also the neurotransmitter most affected in Alzheimer disease. Step 3: In Step 3, neurotransmitters travel across the synaptic cleft and bind to receptors on the postsynaptic membrane, delivering the impulse to the next neuron or target cell. Different neurotransmitters bind to different receptors. ACh is an important neurotransmitter found in the central, peripheral, somatic, autonomic, and parasympathetic nervous systems. It stimulates all skeletal muscles and viscera. It is also the neurotransmitter most affected in Alzheimer disease. Step 4: In Step 4, ion channels on the postsynaptic membrane open, allowing ions such as sodium, potassium, and calcium to flow into the postsynaptic cell causing an inhibitory or excitatory effect. The neurotransmitter ACh, for example, activates the opening of postsynaptic cation channels allowing cations to flow from the synaptic cleft into the postsynaptic cell leading to an excitatory effect. Stage 5: Signal Termination After an axon terminal fires its neurotransmitters to deliver a signal, the neurotransmitters must be rapidly removed from the synaptic cleft. This enables the axon terminal and postsynaptic cell to engage in another cycle of signal generation. The removal of neurotransmitters can be achieved the following ways: Neurotransmitters may diffuse away from the synaptic cleft Taken up by the presynaptic cell to be recycled for the next signal release or Broken down by enzymes in the synaptic cleft. The breakdown of ACh by the enzyme acetylcholinesterase (or AChE)

is an example of this degradation process. AChE is an enzyme responsible for degrading ACh. It is found mainly in neurons.




Recall Exercise The scrambled word is the answer to the question below:

Scrambled word: SRASEOLHCIETEN

1. _________________ Refers to a neuron that is on the "sending" side of the synapse.

Scrambled word: RINOEPLAZRTOAI

2. _________________ The process during which potassium ion channels open, allowing positively charged potassium to rush out of the cell.

Scrambled word: SXSYOTOIEC

3. _________________ The process by which the influx of calcium triggers the synaptic vesicles to release neurotransmitter into the synaptic cleft.

ANSWERS: 1. PRESYNAPTIC, 2. REPOLARIZATION, 3. EXOCYTOSIS




Chemical Classification There are more than 50 known and potential neurotransmitters in the human body. Chemically, they can be classified into 5 groups.

Chemical Classifications of Neurotransmitters

Chemical Classification Location Function

ACh CNS, PNS, autonomic, and parasympathetic nervous systems

Stimulates all skeletal muscles and viscera

Biogenic Amines: catecholamine, indolamine, norepinephrine

CNS, autonomic nervous system

Regulate emotional behavior and biological clock

Amino Acids: gamma-aminobutyric acid (GABA), glycine, aspartate, glutamate

CNS Alt er neuronal discharge

Neuropeptides: endorphin, dynorphin, enkephalin, tachykinin, somatostatin, cholecystokinin

CNS, PNS Mediate transmission of pain signals

Purines Adenosine triphosphate (ATP)

CNS, PNS Entrance neurotransmission

Novel Messengers: adenosine triphosphate (ATP), nitric oxide (NO), carbon monoxide (CO), endocannabinoid

CNS, PNS Enhance neurotransmission, may influence learning and memory

Alzheimer Link Proper brain function is dependent upon the correct balance of neurotransmitters.

AD is associated with insufficient amounts of certain neurotransmitters, such as ACh.



outside of Novartis Pharmaceuticals Corporation. Ch-2, S-2,

Functional Classification Neurotransmitters can also be classified according to function. The 2 functional classifications of neurotransmitters are:

Effect: whether a neurotransmitter excites or inhibits changes in membrane potential, or both.

o ACh excites skeletal muscle and inhibits smooth muscle, such as cardiac muscle.

o Norepinephrine also selectively excites and inhibits. o Some amino acids are entirely inhibitory, while others are excitatory.

Mechanism of action: whether a neurotransmitter acts directly or indirectly

through a second messenger. o ACh and amino acids are direct-acting neurotransmitters. o Biogenic amines and peptides are indirect neurotransmitters.

Alzheimer Link Treatments for AD include medications that target the problems of neurotransmitter imbalances. For example: Drugs known as cholinesterase inhibitors increase ACh availability by reversibly

blocking the enzyme that degrades ACh.

Glutamate-receptor blockers decrease glutamatergic neurotransmission, which is involved in cell death, by blocking N-methyl-D-aspartate (NMDA) receptors.




Recall Exercise Label each statement as TRUE or FALSE.

1. ________ ACh and amino acids are indirect neurotransmitters.

2. ________ Proper brain function is dependent upon the correct balance of neurotransmitters.

3. ________ Drugs known as cholinesterase inhibitors increase ACh availability.

4. ________ ACh excites cardiac muscle and inhibits smooth muscle, such as skeletal muscle.

5. ________ GABA is an amino acid that is found in the PNS.

ANSWERS: 1. False, 2. True, 3. True, 4. False, 5. False




Acetylcholine and Its Role in Neurotransmission

Importance

Of the neurotransmitters, ACh is the best understood because it is released at neuromuscular junctions, which are easier to study than the synapses that are buried in the CNS.

It is also an important neurotransmitter because of its distribution and influence

throughout the nervous system.

All autonomic preganglionic nerve fibers in the CNS—and all parasympathetic postganglionic nerve fibers in the PNS—release ACh.

All somatic motor neurons release ACh at their synapses with skeletal

muscle fibers.

Synthesis ACh is synthesised within the

cytoplasm of axon terminals from acetic acid (as acetyl-CoA) and choline and the process is catalysed by the enzyme choline acetyltransferase (ChAT)

After the synthesis most of the ACh is transferred to the synaptic vesicles for later release.

Arrival of a nerve impulse at the

motor nerve terminal triggers the release of ACh into the synaptic cleft.

Alzheimer Link

ACh neurotransmitters are decreased by AD. Medications that increase ACh availability may be used in the treatment for the cognitive symptoms of AD.




Receptors The effect of ACh on cell membranes (whether it excites or inhibits membrane potential) is guided by the receptors to which it attaches. ACh binds to 2 types of receptors, which explains why it is able to excite some muscles and inhibit others. The 2 types of receptors ACh binds to are:

Nicotinic receptors, which are located on: o Neuromuscular junctions of skeletal muscles in the somatic nervous system o All sympathetic and parasympathetic neurons o Hormone-producing cells of the adrenal medulla

Muscarinic receptors, which are located on:

o All effector neurons in parasympathetic target organs o Some sympathetic targets

Degradation After it is released by the axon terminal of a neuron into the synaptic cleft and

binds to a receptor, ACh is degraded by enzymes, including acetylcholinesterase (AChE), which are located in the cleft or on the postsynaptic membrane.

Degradation of ACh frees the ACh receptors on the postsynaptic neuron. The breakdown of ACh into its component parts also returns choline to the presynaptic terminals to be recycled back into ACh.

AChE is primarily located in neurons. In the thalamus, AChE has been found in areas

specifically related to cognitive functions.

In the AD brain, the overall level of AChE is decreased. In patients with late AD, the number of cholinergic neurons are reduced.

Knowing the location of ACh receptors helps make it possible to select

medications that can provide the desired stimulatory or inhibitory effect.

Cholinesterase inhibitors used in the treatment of AD inhibit an enzyme

involved in ACh degradation (AChE), which may enhance cholinergic activity.




Glutamate and Its Role in Learning and Memory Glutamate is one of the amino acid neurotransmitters and is present in especially

high concentration throughout the brain. It is an extremely potent neurotransmitter and is recognized as the primary "fast" excitatory neurotransmitter in the CNS.

Many neuronal pathways essential to learning and memory use glutamate as a

neurotransmitter. The 2 main ion channel glutamate receptors are: o Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors o N-methyl-D-aspartate (NMDA) receptors

AMPA receptors mediate rapid depolarization at most glutamatergic synapses in the

brain and spinal cord where glutamate is a neurotransmitter.

NMDA receptors can act as a calcium channel in postsynaptic neuronal cell membranes and are involved in memory formation. However, activation of NMDA receptors requires the simultaneous depolarization of the postsynaptic membrane. Therefore, NMDA receptor function is dependent upon the activation of AMPA receptors at nearby synapses.

Alzheimer Link Glutamate neurotransmission is severely disrupted in patients with AD, causing

neuronal cell death via a cascade of events.

The cascade is triggered by excessive activation of NMDA receptors in response to build-up of glutamate in synaptic clefts, which is itself a result of neuron damage.

Excessive NMDA activity increases uptake of calcium in neurons, causing the

generation of free radicals, such as NO, which kill surrounding neurons by starving them of oxygen (oxidative stress).

The accumulation of intracellular free radicals mediates the toxic effects.

Unregulated glutamate activity is linked to neuronal injury after stroke or acute brain injury.




Recall Exercise Complete the statements below using the following terms:

AChE Nicotinic receptors NMDA receptors Ach

1. Synthesized in synaptic vesicles within the axon terminals by the enzyme choline acetyltransferase _________________.

2. Excessive NMDA activity increases uptake of calcium in neurons, causing the generation of free radicals which kill surrounding neurons via oxidative stress _________________.

3. Located on motor endings of skeletal muscles in the somatic nervous system _________________.

4. Overall levels are decreased in the AD brain _________________.

ANSWERS: 1. Ach, 2. NMDA receptors, 3. Nicotinic receptors, 4. AChE




Chapter Summary Neurotransmission is the mechanism by which neurons transmit signals to and from

the body and CNS via a combination of electrical and chemical impulses that travel between cells.

The neuronal structures involved in neurotransmission include the: o Dendrites, which sense stimulation o Axons, where resting membrane potential is transformed into action potential o Axon terminals, where synaptic vesicles are triggered to release

neurotransmitter

Depolarization followed by repolarization is the electrochemical process that creates a wave by which neurons transmit signals to other neurons and target cells.

Neurotransmitters deliver impulses by traveling across the synaptic cleft and bind to receptors on the postsynaptic membrane.

Once bound, neurotransmitters continue to affect postsynaptic receptors, blocking them from receiving other signals. Therefore, their effect must be terminated once the impulse is delivered.This is achieved by 3 different mechanisms:

o Degradation of the neurotransmitter by enzymes o Reuptake of the neurotransmitter into the presynaptic axon terminal o Diffusion of the neurotransmitter away from the synapse

There are more than 50 known and potential neurotransmitters, which may be

classified according to their chemical composition or function.

ACh is an important neurotransmitter found throughout the central, peripheral, somatic, autonomic, and parasympathetic nervous systems.

The enzyme choline acetyltransferase is responsible for synthesizing ACh in the

synaptic vesicles.

ACh functions as both an exciter and an inhibitor of membrane potential because it binds to 2 types of postsynaptic receptors:

o Nicotinic receptors o Muscarinic receptors

AChE is an enzyme found in the synaptic cleft and postsynaptic membrane that

degrades ACh. o AChE is primarily located in neurons. o In the AD brain, the overall level of AChE is decreased. In patients with late

AD, the number of cholinergic neurons are reduced.

Glutamate is a potent excitatory neurotransmitter found in the CNS and plays an important role in learning and memory.




The 2 receptors for glutamate work together to enable neurotransmission. o AMPA receptors mediate rapid depolarization at most synapses of the brain

and spinal cord. o NMDA receptors act as a calcium ion channel in postsynaptic neuronal cell

membranes that are essential for learning and require the simultaneous depolarization of the postsynaptic membrane by AMPA.




Self-check

1. Neurotransmission begins with the arrival of a(n) _____________ at the presynaptic axon terminal. A. Depolarization B. Action potential C. Repolarization D. Axon terminal

2. All of the following statements are true about the process of neurotransmission,

EXCEPT: A. Depolarization is the process by which resting membrane potential is transformed

into action potential. B. The synaptic vesicles release neurotransmitter into the synaptic cleft by a process

called exocytosis. C. The stronger the stimuli, the greater the number of synaptic vesicles releasing

neurotransmitters and the greater the effect on the postsynaptic cell. D. During repolarization, potassium ion channels close, preventing positively

charged potassium to rush out of the cell.

3. The event that triggers the synaptic vesicles to release neurotransmitter into the synaptic cleft is: A. Depolarization of the axon B. An influx of calcium at the axon terminal C. Opening of ion channels on the postsynaptic membrane D. Binding of neurotransmitter to the receptor on the postsynaptic membrane

4. Which neurotransmitter stimulates all skeletal muscles and viscera?

A. Acetylcholine B. Biogenic amines C. Amino acids D. Neuropeptides

5. The effect of ACh on cell membranes (whether it excites or inhibits membrane

potential) is guided by: A. Whether it is found in the CNS or PNS B. The receptors to which it attaches C. Which enzyme it is degraded by D. Activation of AMPA receptors




6. All of the following statements are true about glutamate, EXCEPT:

A. Glutamate is present in high concentration in the central nervous system. B. Glutamate and its receptors play an important role in learning and memory. C. Glutamate neurotransmission is only mildly disrupted in patients with AD. D. Glutamate is an extremely potent neurotransmitter.

ANSWERS: 1. B, 2. D, 3. B, 4. A, 5. B, 6. C




Glossary Acetylcholine (ACh): An ester of acetic acid and choline that is the neurotransmitter at somatic neuromuscular junctions, the entire parasympathetic nervous system and central nervous system. Acetylcholinesterase (AChE): An enzyme that stops the action of acetylcholine. It is present in various body tissues, including muscles, nerve cells, and red blood cells. Action potential: Also known as a nerve impulse; a local reversal of the charge across an excitable cell membrane that is propagated quickly along the length of the membrane. In humans, most of the cells that conduct action potentials are neurons or muscles. Adrenal medulla: The central tissue of the adrenal gland. It is filled with chromaffin cells, which as derived from the neural crest and are very much like postsynaptic ganglion cells. Afferent (sensory) division: The division of the brain that is responsible for conveying impulses from the receptors of sense organs to the central nervous system. Amygdala: A spherical collection of nuclei of the central nervous system, lying inside the front tip of the temporal lobe of each cerebral hemisphere. Anterior: Before or in front of; in anatomical nomenclature, refers to the ventral or abdominal side of the body. Association area: Area of the cerebral cortex connected to motor and sensory areas of the same side, to similar areas on the other side, and to other regions of the brain (eg, the thalamus). It integrates motor and sensory functions. Association neurons (interneurons): A neuron within the central nervous system (not directly connected to the periphery) that is neither sensory nor motor. There are two principal types: (a) those that convey information over short distances and (b) those that convey information from region to region. Autonomic nervous system: The part of the nervous system that controls involuntary bodily functions. It is inappropriately named because rather than being truly "autonomic," it is intimately responsive to changes in somatic activities. The autonomic nervous system consists of motor nerves to visceral effectors: smooth muscle; cardiac muscle; glands such as the salivary, gastric, and sweat glands; and the adrenal medullae. Axon: A process of a neuron that conducts impulses away from the cell body. Axon terminal: The end of an axon.




Brain stem: The stemlike part of the brain that connects the cerebral hemispheres with the spinal cord. It comprises the medulla oblongata, the pons, and the midbrain. Central nervous system (CNS): The brain and spinal cord constitute the central nervous system. Cerebellum: The large posterior brain mass lying dorsal to the pons and medulla and ventral to the tentorium cerebelli (the process of the dura between the cerebrum and cerebellum supporting the occipital lobes) and posterior portion of the cerebrum; it consists of 2 lateral hemispheres united by a narrow middle portion, the vermis. Cerebral cortex: The thin, convoluted surface layer of gray matter of the cerebral hemispheres (the cerebrum), consisting principally of cell bodies of neurons arranged in layers, as well as numerous fibers. Most of the cerebral cortex has 6 histologically distinct horizontal cortical layers. Cerebrospinal fluid: The sodium-rich, potassium-poor tissue fluid of the brain and spinal cord, which supplies nutrients and removes waste products; it is also a watery cushion that absorbs mechanical shock to the central nervous system. Circadian rhythm: Diverse yet predictable changes in physiological variables, including sleep, appetite, temperature, and hormone secretion, over a 24-hour period. Cranial nerves: The 12 pairs of nerves (CN I–CN XII) originating in the brain stem and mainly controlling the activities of the face and head. Cytoplasm: The protoplasm of a cell outside the nucleus. Dendrite: A short spike-shaped cell process. The term usually refers to the branched, tapering cell processes of neurons. Incoming synapses form on the neuronal dendrites, which often arborize, sometimes extensively. Depolarization: A reversal of charges at a cell membrane; an electrical change in an excitable cell in which the inside of the cell becomes positive (less negative) in relation to the outside. This is the opposite of polarization and is caused by a rapid inflow of sodium ions. Diencephalon: The second portion of the brain; includes the epithalamus, thalamus, metathalamus, and hypothalamus. Dura: A tough, fibrous membrane forming the outer covering of the central nervous system. Also called dura mater. Efferent (motor) division: The part of the brain that is responsible for conduction of impulses from the brain or spinal cord to the periphery.




Endoplasmic reticulum: A cell organelle that is a complex network of membranous tubules in the cytoplasm between the nuclear and cell membranes; it is visible only with an electron microscope. Epidural space: The space outside the dura mater of the brain and spinal cord. Epithalamus: The uppermost portion of the diencephalon of the brain. It includes the pineal body, trigonum habenulae, habenula, and habenular commissure. Exocytosis: The discharge of particles from a cell, including waste or chemical transmitters, that are too large to pass through the cell membrane by diffusion. Frontal lobe: The anterior part of a cerebral hemisphere. Ganglia: Masses of nervous tissue composed principally of neuron cell bodies and lying outside the brain or spinal cord (eg, the chains of ganglia that form the main sympathetic trunks; the dorsal root ganglion of a spinal nerve). Glial cells: The branching nonneural cells of the neuroglia (the supporting tissue of the central nervous system). Glutamate: A salt of glutamic acid that functions as the brain’s main excitatory neurotransmitter. Gray matter: Nerve tissue composed mainly of the cell bodies of neurons rather than their myelinated processes. The term is generally applied to the gray portions of the central nervous system. Gyri: The convolutions of the cerebral hemispheres of the brain. Hippocampus: An elevation of the floor of the inferior horn (the lower or downward prolongation of a part or structure of the body) of the lateral ventricle of the brain, occupying nearly all of it. The hippocampus could be important in establishing new memories. Homeostasis: The state of dynamic equilibrium of the internal environment of the body that is maintained by the ever-changing processes of feedback and regulation in response to external or internal changes. Hypothalamus: The ventral half of the diencephalon of the brain. It is the regulator of the essential homeostatic balance of body fluids, salt concentrations, temperature, and energy metabolism. It is also the governor of reproductive cycles and certain emotional responses. Inferior: The undersurface of an organ, or, indicative of a structure below another structure.




Ion: An atom or group of atoms that has lost one or more electrons and has a positive charge, or has gained one or more electrons and has a negative charge. Ion channel: A protein that spans the lipid bilayer of the cell membrane and regulates the movement of charged particles (eg, electrolytes) into and out of cells. Limbic system: A group of subcortical structures (such as the hypothalamus, the hippocampus, and the amygdala) of the brain that are concerned especially with emotion and motivation. Lumbar vertebrae: The 5 vertebrae between the thoracic vertebrae and the sacrum. Medulla oblongata: The lowest part of the brain stem, continuous with the spinal cord above the level of the foramen magnum (opening through which the spinal cord passes from the brain) in the occipital bone. It regulates heart rate, breathing, blood pressure, and other reflexes, such as coughing, sneezing, swallowing, and vomiting. Midbrain: The 3 parts (corpora quadrigemina, the crura cerebri, and aqueduct of Sylvius) that together connect the pons and cerebellum with the hemispheres of the cerebrum. It contains reflex centers for eye and head movements in response to visual and auditory stimuli. Motor area: Posterior part of the frontal lobe anterior to the central sulcus, from which impulses for volitional (willful, or out of choice) movement arise. Motor (efferent) neurons: A neuron that carries impulses from the central nervous system either to muscle tissue to stimulate contraction or to glandular tissue to stimulate secretion. Muscarinic receptor: Cholinergic receptors on autonomic effector cells (and also on some autonomic ganglion cells and in some central neurons) that are stimulated by muscarine and parasympathomimetic drugs and blocked by atropine. Myelin sheath: Layers of the cell membrane of Schwann cells in the peripheral nervous system or oligodendrocytes in the central nervous system that wrap nerve fibers, providing electrical insulation and increasing the velocity of impulse transmission. Neuron: A nerve cell, the structural and functional unit of the nervous system. A neuron consists of a cell body (perikaryon) and its processes, an axon and one or more dendrites. Neurons function in initiation and conduction of impulses. Neurotransmission: The transmission of nerve impulses across a synapse. Neurotransmitter: A substance (as norepinephrine or acetylcholine) that transmits nerve impulses across a synapse. Nicotinic receptor: Cholinergic receptors of autonomic ganglion cells and motor end-plates of skeletal muscle that are stimulated by low doses of nicotine and blockaded by high doses of nicotine or by tubocurarine.




Nucleus: The structure within a cell that contains the chromosomes. It is responsible for the cell's metabolism, growth, and reproduction. Occipital lobe: The posterior region of a cerebral hemisphere, shaped like a 3-sided pyramid. Oligodendrocyte: Neuroglial cells having few and delicate processes. Organelle: A specialized structure within a cell that performs a distinct function. Examples of organelles are the endoplasmic reticulum, the Golgi apparatus, lysosomes, mitochondria, proteasomes, and ribosomes. Oxidative stress: The cellular damage caused by oxygen-derived free radical formation. Parasympathetic nervous system: The craniosacral division of the autonomic nervous system. Preganglionic fibers originate from nuclei in the midbrain, medulla, and sacral portion of the spinal cord. Parietal lobe: The division of each cerebral hemisphere lying beneath each parietal bone. Peripheral nerve: Any nerve that connects the brain or spinal cord with peripheral receptors or effectors. Peripheral nervous system (PNS): The portion of the nervous system outside the central nervous system. It consists of 12 pairs of cranial nerves and 31 pairs of spinal nerves. These nerves contain sensory and somatic motor fibers and the motor fibers of the autonomic nervous system. Pineal gland: An endocrine gland in the brain, shaped like a pine cone. It is located in a pocket near the splenium of the corpus callosum. It is the site of melatonin synthesis, which is inhibited by light striking the retina. Polarized: The electrical state that exists at the cell membrane of an excitable cell at rest; the inside is negatively charged in relation to the outside. The difference is created by the distribution of ions within the cell and in the extracellular fluid. Pons: A broad mass of chiefly transverse nerve fibers in the mammalian brain stem lying ventral to the cerebellum at the anterior end of the medulla oblongata. Posterior: Pertaining to or located at or toward the back; dorsal.




Postsynaptic neuron: A neuron to the cell body or dendrite of which an electrical impulse is transmitted across a synaptic cleft by the release of a chemical neurotransmitter from the axon terminal of a presynaptic neuron. Presynaptic neuron: A neuron from the axon terminal of which an electrical impulse is transmitted across a synaptic cleft to the cell body or one or more dendrites of a postsynaptic neuron by the release of a chemical neurotransmitter. Repolarization: Restoration of the polarized state at a cell membrane (negative inside in relation to the outside) following depolarization as in muscle or nerve fibers. Resting membrane potential: The difference in transmembrane potential of a cell when it is at rest (fully repolarized). Reuptake: The reabsorption by a neuron of a neurotransmitter following the transmission of a nerve impulse across a synapse. Ribosome: A cell organelle made of ribosomal RNA and protein. In protein synthesis, they are the site of messenger RNA attachment and amino acid assembly in the sequence ordered by the genetic code carried by mRNA. Schwann cell: One of the cells of the peripheral nervous system that form the myelin sheath and neurilemma of peripheral nerve fibers. Sensory area: Any area of the cerebral cortex in which sensations are perceived. Sensory (afferent) neurons: A neuron that conducts sensory impulses toward the brain or spinal cord. Soma: The body of a nerve cell, from which axons, dendrites, etc, project. Somatic nervous system: The parts of the peripheral nervous system that are concerned with the transmission of impulses to and from the nonvisceral components of the body, such as the skeletal muscles, bones, joints, ligaments, skin, and eye and ear. Spinal cord: Part of the central nervous system, the spinal cord is an ovoid column of nerve tissue 40 to 50 cm long. It extends from the medulla to the second lumbar vertebra. It is within the spinal (vertebral) canal, protected by bone, and directly enclosed in the meninges. Spinal nerves: The nerves emerging from the spinal cord. Stimuli: That which can elicit or evoke response in a muscle, nerve, gland, or other excitable tissue, or cause an augmenting action upon any function or metabolic process. Sulci: Grooves or furrows on the surface of the brain, bounding the several convolutions or gyri; fissures.




Superior: Situated nearer the vertex of the head in relation to a specific reference point; opposite of inferior. Sympathetic nervous system: The part of the autonomic nervous system that is concerned especially with preparing the body to react to situations of stress or emergency. Synaptic cleft: The space between neurons at a nerve synapse across which a nerve impulse is transmitted by a neurotransmitter. Also called the synaptic gap. Synaptic vesicle: A small secretory vesicle that contains a neurotransmitter. It is found inside an axon near the presynaptic membrane, and releases its contents into the synaptic cleft after fusing with the membrane. Telodendria: The terminal arborization (arrangement of branching parts) of a nerve fiber. Used originally of dendrites, but is now used especially of the main arborization of an axon. Temporal lobe: A large lobe of each cerebral hemisphere that is situated in front of the occipital lobe and contains a sensory area associated with the organ of hearing. Thalamus: The largest subdivision of the diencephalon on either side, consisting chiefly of an ovoid gray nuclear mass in the lateral wall of the third ventricle. Vertebral column: The portion of the axial skeleton consisting of vertebrae (7 cervical, 12 thoracic, 5 lumbar, the sacrum, and the coccyx) joined together by intervertebral disks and fibrous tissue. It forms the main supporting axis of the body, encloses and protects the spinal cord, and attaches the appendicular skeleton and muscles for moving the various body parts. White matter: Nerve tissue of the spinal cord and brain, composed mainly of myelinated nerve fibers.

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