NERVOUS SYSTEM 2003-04
Based on lecture and text material, you should be able to do the following:
Control Systems; General
； Give a concise account of homeostasis
； Define and explain positive and negative feedback
； Explain feed-forward control
； Give neural examples of different types of feedback control
； Describe the important anatomical structures of a neuron and relate each structure to a
； Define resting membrane potential and describe its electrochemical basis
； Compare and contrast graded and action potentials
； Explain how action potentials are generated and propagated along neurons
； Define absolute and relative refractory periods and explain their significance
； Define saltatory conduction and compare it to conduction along unmyelinated fibers
； Define a synapse and describe how information is transferred across them
； Distinguish between excitatory and inhibitory postsynaptic potentials
； Describe how synaptic events are integrated and modified
； Define summation and differentiate between temporal and spatial summation
； Define neurotransmitter and describe how they are released and subsequently removed
； Describe common patterns of neuron organization and neuronal processing
； Describe the basic concept of sensory transduction
； Compare and contrast receptor and action potentials
； Discuss the mechanisms of sensory coding of information
； Compare and contrast stretch, flexor and crossed extensor reflexes
Sensation Awareness of internal and external events
Perception Assigning meaning to a sensation
Central Nervous System The brain and spinal cord
Peripheral Nervous System All nervous system structures outside the CNS; i.e. nerves (including (PNS) the cranial nerves), ganglia and sensory receptors
Neuroglia (neuro = nerve; glia = glue) Non-excitable cells of neural tissue that
support, protect, and insulate neurons
Neuron Cell of the nervous system specialized to generate and transmit nerve
Dendrite (dendr = tree) branching neuron process that serves as a receptive or
Axon (axo = axis) Neuron process that conducts impulses
Myelin Sheath Fatty insulating sheath the surrounds all but the smallest nerve fibers
Sensory Receptor Dendritic end organs, or parts of other cell types, specialized to
respond to a stimulus
Resting Potential The voltage difference which exists across the membranes of all cells
due to the unequal distribution of ions between intracellular and
Graded Potential A local change in membrane potential that declines with distance and
is not conducted along the nerve fiber
Action Potential A large transient depolarization event, which includes a reversal of
polarity that is conducted along the nerve fiber
Saltatory Conduction Transmission of an action potential along a myelinated nerve fiber in
which the nerve impulse appears to leap from node to node
Synapse (synaps = a union) Functional junction or point of close contact
between two neurons or between a neuron and an effector cell
Neurotransmitter Chemical substance released by neurons that may, upon binding to
receptors or neurons or effector cells, stimulate or inhibit those cells
Sensory Transduction Conversion of stimulus energy into a nerve impulse
Receptor Potential A graded potential that occurs at a sensory receptor membrane
I. BASIC CONCEPTS OF CONTROL SYSTEMS
A. TYPES OF CONTROL SYSTEMS
1) Endocrine (Hormonal) Control - slow general control
2) Neural Control - fast specific control
B. WHAT IS CONTROLLED?
Homeostatic Control - maintains a state of dynamic equilibrium
； Adaptive Responses to Environmental Change - produce appropriate responses to internal
and external changes.
C. COMPONENTS OF A CONTROL SYSTEM
1) Sensors (Receptors)
2) Afferent Pathways
3) Comparators (Integrators)
4) Efferent Pathways
Afferent and efferent pathways can be neural or hormonal.
D. TYPES OF CONTROL
Negative Feedback Control
； Very common
； Maintains homeostasis
； Allows for adaptive responses to environmental (external) stimuli
； Examples include pain withdrawal reflex and "fight or flight" response.
Positive Feedback Control
； Relatively Rare
； Never creates homeostasis
； Enhances change: causes changes to occur faster and to deviate further from starting values.
； Controls episodic events
； Self perpetuating and quite explosive
； Examples include ionic events associated with generations of action potentials, child birth,
hormonal control of ovulation.
； Produces change in anticipation of need for change
； Usually associated with input from "Higher Centers" or from "Other Inputs"
； Examples include change in the breathing rate in anticipation of exercise and changes in the
lining of uterus during menstrual cycle, in anticipation of pregnancy.
II. ORGANIZATION OF THE NERVOUS SYSTEM
A. THE CENTRAL NERVOUS SYSTEM (CNS):
Includes brain and spinal cord, serves as a primary integrating and control center
B. THE PERIPHERAL NERVOUS SYSTEM (PNS):
Consists of all the nerves, including
Cranial nerves which arise directly from the brain (12 pairs in human)
Spinal nerves, which arise from the spinal cord (32 pairs in human). Provides communication lines between the CNS and the rest of the body.
There are two functional divisions of the PNS:
1. Sensory (Afferent) Nervous System
； Conveys impulses to the CNS from sensory receptors
； Has two sub-divisions:
Somatic sensory; conveys information from the skin, muscles joints, and
Visceral sensory; conveys information from the viscera (internal organs)
2. Motor (Efferent) Nervous System
； Conveys information from the CNS to the effectors (muscles and glands)
； Has two sub-divisions:
Somatic motor N.S. conveys information to skeletal muscles, is under
voluntary control, its effects are always stimulatory.
Autonomic N.S. conveys information to cardiac and smooth muscles
and glands; is under involuntary control, its effects
can be either stimulatory or inhibitory.
Has two functional sub-divisions:
1) Sympathetic Nervous System
2) Parasympathetic nervous System
(These two systems usually have opposite effects on the same
visceral organs. If one stimulates, the other inhibits)
III. NERVOUS TISSUE
Made up of two cell types:
1. Supporting Cells (glial cells)
2. Neurons (nerve cells)
A. SUPPORTING CELLS (or GLIAL CELLS or GLIA):
Make up more than 90% of the cells in the nervous system.
There are six different types of cells involved; each type has different function(s), for example:
； Some form a scaffolding or glue, which holds the nervous tissue together,
； Some assist neurons by maintaining optimal environment around them,
； Two types form myelin, which plays an important role in regulating the speed with which
nerves conduct information (action potentials).
； Unlike the neurons, which are amitotic, they reproduce themselves throughout life; for this
reason most brain tumors are gliomas, formed by uncontrolled proliferation of glial cells.
； Are highly specialized
； Are one of a few types of excitable cells (able to fire action potentials) in the body
； Conduct messages in the form of action potentials (nerve impulses) from one part of the
body to another
； Are amitotic; they can not replace themselves; they do, however, have extreme longevity
； Have a high metabolic rate and can not survive for more than a few minutes without oxygen
； Have a cell body or soma and numerous thin processes (extensions)
； Most cell bodies of neurons are located in the CNS where they are protected by the cranium
and vertebral column
； Within cell bodies all standard organelles are contained
1. Types of neuron processes:
Dendrites are processes that receive information, they are input regions of the neuron but they
do not have the ability to generate action potentials.
Axons are processes that can generate and conduct action potentials, they arise at an area
associated with neuron's soma called the axon hillock or spike initiation zone (trigger
zone); they may be very short or very long depending on where they are conducting
information; can give off branches called axon collaterals; finally they form synapses
at their terminals.
2. Structural Classification of Neurons:
Neurons come in many shapes and sizes but are generally classified based on the extensions or processes extending from their cell bodies.
There are three main structural groups of neurons:
； Have many dendrites and one axon
； Most common type in the CNS
； Have one dendrite and one axon on opposite sides of the cell body
； Rare, found only in specialized sense organs such as the eye and the olfactory
； Both dendrites and axon arise from a single extension from the cell body,
； Are common sensory neurons found in the PNS.
3. Functional Classification of Neurons:
Sensory neurons (unipolar and some bipolar)
； All are afferent - they conduct action potentials from sensory receptors to the
； Their somas, with a few exceptions, are found in the PNS
Motor Neurons (multipolar)
； Are all efferent - they conduct action potentials away from the CNS to the effector
organs (muscles or glands)
； Their somas are found only in the CNS
Interneurons (multipolar but with much diversity)
； Conduct action potentials between other neurons
； Often connect sensory with motor neurons and integrate their functions
； Found only in the CNS.
； All biological membranes are semipermeable +； [Na] is 10-12x higher outside the cell compared to inside the cell +； [K] is 30x greater inside the cell compared to outside the cell
； The inner membrane face is always relatively more negative than outer face (at resting
A. BASIC PRINCIPLES OF ELECTRICITY
All cells in the body have an unequal distribution of ions (concentration gradient) and charged molecules (electrical gradient) across their membranes. Indeed, all have a net negative balance inside relative to outside (differences are always expressed as inside relative to outside).
Because opposite charges attract, there is a driving force which would lead to ions flow if not for the presence of the membrane. This represents a potential energy, which is called the potential difference or membrane potential, the measure of this potential energy is called voltage and is expressed in volts or millivolts.
This membrane potential is present in all cells, including neurons and muscle cells when they are at
rest (are not firing action potentials), and is called the resting membrane potential, or simply resting
potential. The size of resting potential ranges from -20 to -200 millivolts in different cells, in neurons it ranges from -50 to -100 millivolts and in muscles it averages about - 70 mV.
Actually, neurons and muscle cells are unique. Unlike all other cells, they have the ability to actively change the potential across their membranes in a rapid and reversible way. The rapid reversal of membrane potential is referred to as an action potential.
B. SOURCE OF RESTING MEMBRANE POTENTIAL
Source of the potential difference is primarily due to:
++1) Imbalance of Na and K across the membrane
2) Differences in the relative permeability of the membrane to these two ions
Almost all membranes are more permeable to potassium since there are a large number +of K leak channels that are always open
3) There are relatively few such channels for sodium
++How is the resting membrane potential maintained since with time, K leaves the cell and Na
enters the cytoplasm all the time?
++It depends on the presence of the Na/K pump; a carrier protein found in the membrane that + +transports 2 Kions into the cell and 3 Na ions out, with the expenditure of one ATP.
C. GRADED POTENTIALS
Graded potentials are short-lived local changes in membrane potential due to:
； Changes in membrane permeability to any ion (and hence the flow and distribution of that
ion across the membrane) or
； Anything that changes the concentration of ions on either side of the membrane.
The larger the change in membrane permeability or ion distribution, the larger the change in membrane potential (hence the name graded potentials).
The following changes in membrane potential are associated with graded potentials (and as you will see soon, action potentials as well):
1) Depolarization: membrane potential decreases (becomes less negative)
2) Hyperpolarization: membrane potential increases (becomes more negative)
Following either 1 or 2 membrane potential returns to resting levels as a result of repolarization.
The site of depolarization moves along the membrane but the magnitude of the
depolarization decreases rapidly with distance.
Graded potentials can be used to communicate signals over short distances
D. ACTION POTENTIALS
Some membranes have special features that make them "excitable". If stimuli (anything which disturbs the membrane potential) which are depolarizing and of increasing magnitude are applied to these membranes, a point is reached at which a fast, transient, self-propagating event occurs; an action potential.
Generation of an Action Potential
Whether an action potential (AP) is generated or not depends on the strength of depolarizing
stimulus. Stimuli can be:
Only the latter two stimuli can depolarize the membrane to its threshold potential, which for most neurons is between -30 and -50 mV, or about 15 mV above membrane's resting potential.
Threshold must be reached before an AP can be fired!
Molecular Events Underlying the Action Potential:
+The membrane of all excitable cells contains two special gated channels. One is a Na channel and +the other is a K channel and both are VOLTAGE GATED. At rest, virtually all of the
voltage-gated channels are closed, potassium and sodium can only slowly move across the membrane, through the passive "leak" channels.
The first thing that occurs when a depolarizing graded potential reaches the threshold is that the +++voltage gated Na channels begin to open and Na influx into the cell exceeds K efflux out of
+As more Na enters the cell, the membrane at this site becomes even more depolarized, which opens +even more voltage gated Na channels.
At this point, the process becomes independent of the original stimulus. Even if the stimulus were now taken away, a chain of events has been set in motion that cannot be stopped. This gives rise to a positive feedback cycle known as the Hodgkin Cycle.
Two things happen next:
1) As the membrane depolarizes further and the cell becomes positive inside and negative +outside, the flow of Na will decrease. +2) Even more importantly, the v- gated Na channels close.
Actually these channels have two gates:
- An activation gate, which is closed at rest but opens in response to depolarization, and
- An inactivation gate, which is open at rest but closes slowly in response to depolarization
Hence, during the depolarizing phase both activation and inactivation gates are open. +When the inactivation gates close, Na influx stops and the repolarizing phase takes place.
The time during which each activation gate remains open and each inactivation gate remains closed is genetically predetermined.
+Next, the voltage gated K channels are activated at the time the action potential reaches its peak. + At this time, both concentration and electrical gradients favour the movement of K out of the cell.
+These channels are also inactivated with time but not until after the efflux of K has returned the
membrane potential to, or below the resting level (after hyperpolarization).
1. Only very few ions move across the membrane when AP is fired. Therefore, the actual ++concentration gradients of Na and K across the membrane change very little.
2. APs fired by neurons last only 1-5 msec.
3. Initially, ions move across the membrane only at the spot where the stimulus was
4. Following hyperpolarization, the sodium-potassium pumps help to return the ionic
conditions back to normal very quickly.
Because the series of events becomes self-perpetuating once the membrane is depolarized past threshold, and because all action potentials are of the exact same size, it is said to be an all-or-none event.
As a result, if threshold is not reached, all you get is a graded potential. If threshold is reached, you get an action potential that is always the same. Therefore, both the threshold and suprathreshold stimuli can generate only one response - an action potential.
Absolute and Relative Refractory Periods
During the period of the rising and falling phases of the action potential the system is self- +perpetuating. The voltage-gated Na channels cannot reopen until they return to their original
As a result, the membrane cannot be excited to generate another action potential at this site until the ongoing event is over. This period during which the membrane is completely unexcitable is the absolute refractory period.
Once the membrane potential has returned to resting conditions, another action potential can be +generated. However, before it happens there is a short period during which the voltage gated K
channels are still open producing hyperpolarization, during which the membrane potential is further from threshold and during which a larger than normal stimulus is required to generate an action potential. This is the relative refractory period.
Propagation of Action Potentials
The events we've just described take place at a single site on the membrane. How is this action potential propagated along the axon from one end to the other?
The depolarization, which occurs during the action potential, just like the graded potentials, will set up a current that spreads out from the site of the action potential. Again, just like the graded potentials, it will decay with distance.
+However, if the current spreads to another site on the membrane containing voltage-gated Na
channels and the current still has sufficient voltage to depolarize the membrane to threshold, another AP will be generated at that site.
+Thus, the AP is propagated along the axon by being regenerated by voltage gated Na channels
along that axon.
+In order for this to proceed the density of v-gated Na in a membrane of an axon must be constant
for that axon to propagate APs
Imagine that the propagation of an action potential is like a row of dominos.
If the dominos are too far apart, the action potential will not be propagated.
Speed of conduction (conduction velocity)
Two principle factors determine conduction velocity.
1. Axon Diameter:
； The larger the diameter, the lower the resistance to the spread of the local current
and the faster the impulse can be propagated.
2. The Presence or Absence of Myelin
； Addition of myelin by glial cells around the nerve axon decreases the rate at
which the current decays.
As a consequence: +； Voltage-gated Na channels can be farther apart and are found only within the nodes of
Ranvier, or small areas where there is no myelin
； myelinated neurons can fire action potentials only within the nodes.
Because it takes time to regenerate the action potential at each site along the membrane, the farther apart the nodes of Ranvier, the faster the net movement of the impulse along the axon.
This type of regeneration of action potential at sequential nodes is called saltatory conduction. Can you answer these questions?
Should the propagation of APs be unidirectional or multidirectional? Why? What is the mechanism involved?
E. SYNAPSES AND TRANSMITTER RELEASE
Synapses are the junctions between neurons and the structures they innervate.
There are some specialized neurons, which are connected by gap junctions, and through which ions can flow and, hence, across which action potentials can be directly propagated. Although these are relatively uncommon in the nervous system they are extremely important in the cardiac muscle tissue and will be discussed later.
Most neurons are separated from the object that they innervate by a short gap. These gaps or junctions are very narrow but even so, the action potential cannot jump across them. Instead, electrical activity is usually transferred from the axon terminal to the next cell by a chemical