Fundamentals of the Nervous System and Nervous Tissue

1
Chapter 11

• Fundamentals of the Nervous System and Nervous
  Tissue
• J.F. Thompson, Ph.D. J.R. Schiller, Ph.D. G.
  Pitts, Ph.D.

2
The Nervous System

• The Nervous System is the rapid control system of
  the body
• There are two anatomical divisions to the Nervous
  System
• The Central Nervous System (CNS)
• The Peripheral Nervous System (PNS)
• They work together as a single coordinated whole

3
The Functions of the Nervous System

• There are three interconnected functions
• sensory input
• from millions of specialized receptors
• receive stimuli
• integration
• process stimuli
• interpret stimuli
• motor output
• cause response
• at many effector organs

4
Organization of the Central Nervous System

• the Brain and Spinal Cord
• process integrate information, store
  information, determine emotions
• initiate commands for muscle contraction,
  glandular secretion and hormone release (regulate
  and maintain homeostasis)
• connected to all other parts of the body by the
  Peripheral Nervous System (PNS)

5
Organization of the Peripheral NS

• anatomical connections
• spinal nerves are connected to the spinal cord
• cranial nerves are connected to the brain
• two functional subdivisions
• sensory (afferent) division
• somatic afferents - skin, skeletal muscle,
  tendons, joints
• special sensory afferents
• visceral afferents - visceral organs
• motor (efferent) division
• motor (efferent) neurons
• muscles/glands

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Organization of the PNS (continued)

• motor (efferent) division has two parts
• Somatic Nervous System (SNS)
• voluntary motor neurons
• output to skeletal muscles
• Autonomic Nervous System (ANS)
• involuntary visceral motor neurons
• output to smooth muscle, cardiac muscles and to
  glands
• two cooperative components
• sympathetic division
• parasympathetic division

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Autonomic Nervous System

• Sympathetic Division for muscular exertion and
  for fight or flight emergencies
• Parasympathetic Division for metabolic/
  physiologic business as usual (feed or breed)

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Nervous Tissue

• Review the microanatomy of nervous tissue in lab
  and in the PPT with audio CH11 Histology of
  Nervous Tissue
• Nerve cell physiology is primarily a cell
  membrane phenomenon
• Information transmission differs between
  dendrites and axons

9
Neuron Processes - Dendrites

• short, tapering, highly branched extensions of
  the soma
• not myelinated
• contain some cell organelles
• receptiveinitiate and transmit graded potentials
  (not action potentials) to the cell body

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Neuron Processes - Axons

• A single process that transmits action potentials
  from the soma
• Originates from a cone-shaped axon hillock
• May be long (1 meter) or short (lt1 mm)
• long axons called nerve fibers
• Up to 10,000 terminal branches
• each with an axon terminal that synapses (joins)
  with a neuron or an effector (muscle or gland
  cell)

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Axons (continued)

• Axoplasm the cytoplasm of the axon
• Axolemma the cell membrane of the axon,
  specialized to initiate and conduct action
  potentials (nerve impulses)
• initiated at the axon hillock (trigger zone),
  travels to the axon terminal
• causes release of neurotransmitter from terminal
• neurotransmitters can excite or inhibit
• transfers a control message to other neurons or
  effector cells

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Histology of Neurons Myelin Sheath

• lipid-rich, segmented covering on axons
• most larger, longer axons are myelinated
• dendrites are never myelinated
• myelin protects electrically insulates the axon
• increases the speed of nerve impulses
• myelinated fibers conduct impulses 10-150x faster
  than unmyelinated fibers
• 150 m/sec vs. 1 m/sec

13
Myelinating Cells

• neurolemmocytes (Schwann cells) in the
  Peripheral NS
• oligodendrocytes in the Central NS

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Myelination

• occurs during fetal development and the first
  year of life
• each myelinating cell wraps around an axon up to
  100 times, squeezing its cytoplasm and organelles
  to the periphery
• myelin sheath multiple layers of the cell
  membrane
• neurolemma (sheath of Schwann) outer layer
  containing the bulk of the cytoplasm and cell
  organelles

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Myelinated and Unmyelinated Axons

• Myelinated Fibers
• Myelin sheath
• neurofibril nodes (Nodes of Ranvier) periodic
  gaps in the myelin sheath between the
  neurolemmocytes
• Unmyelinated Fibers
• surrounded by neurolemmocytes but no myelin
  sheath present
• neurolemmocytes may enclose up to 15 axons
  (unmyelinated fibers)

neurolemmocytes guide regrowth of neuron
processes after injury
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Myelination In the Central NS

• Gray matter - unmyelinated cell bodies
  processes
• White matter myelinated processes in various
  fiber tracts

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Classifications of Neurons

• Structural based on the number of processes
  extending from the cell body
• Functional based on the direction (location) of
  nerve impulses
• emphasize the functional classification ?

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Afferent ( Sensory) Neurons

• afferent towards CNS
• nerve impulses from specific sensory receptors
  (touch, sight, etc.) are transmitted to the
  spinal cord or brain (CNS)
• afferent neuron cell bodies are located outside
  the CNS in ganglia

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Efferent ( Motor) Neurons

• efferent away from CNS
• nerve impulses from CNS (brain and spinal cord)
  are transmitted to effectors (muscles, endocrine
  and exocrine glands)
• efferent neuron cell bodies are located inside
  the CNS

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Association Neurons ( Interneurons)

• carry nerve impulses from one neuron to another
• 99 of the neurons in the body are interneurons
• most interneurons are located in the CNS

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Neurophysiology - Definitions

• voltage
• the measure of potential energy generated by
  separated charges
• always measured between two points the inside
  versus the outside of the cell
• referred to as a potential - since the charges
  (ions) are separated there is a potential for the
  charges (ions) to move along the charge gradient

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Neurophysiology - Definitions

• current
• the flow of electrical charge from one point to
  another
• in the body, current is due to the movement of
  charged ions
• resistance
• the prevention of the movement of charges (ions)
• caused by the structures (membranes) through
  which the charges (ions) have to flow

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Neurophysiology - Basics

• Cell interior and exterior have different
  chemical compositions
• Na/K ATPase pumps change the ion concentrations
• a semi-permeable membrane allows for separation
  of ions
• Ions attempt to reach electrochemical equilibrium
• two forces power the movement of ions
• individual ion concentrations (chemical
  gradients)
• net electrical charge (overall charge gradient)
• the balance between concentration (chemical)
  gradients and the electrical gradient known as
  the electrochemical equilibrium
• the external voltage required to balance the
  concentration gradient is the equilibrium
  (voltage) potential

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Neurophysiology - Membrane Ion Channels

• regulate ion movements across cell membrane
• each is specific for a particular ion or ions
• many different types
• may be passive (leaky)
• may be active (gated)
• gate status is controlled
• gated channels are regulated by signal chemicals
  or by other changes in the membrane potential
  (voltage potential)

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Resting Membrane Potential (RMP)

• electrical charge gradient associated with outer
  cell membrane
• present in all living cells
• the cytoplasm within the cell membrane is
  negatively charged due to the charge
  disequilibrium concentrations of cations and
  anions on either side of the membrane
• RMP varies from about -40 to -90 millivolts (a
  net negative charge inside relative to a net
  positive charge outside the cell)

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Resting Membrane Potential (cont.)

• RMP is similar to a battery
• stores an electrical charge and can release the
  charge
• 2 main reasons for this
• ion concentrations on either side of the plasma
  membrane are due to the action of the Na/K
  ATPase pumps
• primarily, Na and Cl- are outside the membrane
  is polarized
• primarily, K, Cl-, proteins- and organic
  phosphates- are inside
• plasma membrane has limited permeability to Na
  and K ions

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Resting Membrane Potential (cont.)

• Resting conditions
• Na/K ATPase pumps 3 Na ions out and 2 K ions
  in per ATP hydrolysis opposing their
  concentration gradients
• concentration gradient drives Na to go into the
  cell
• concentration gradient drives K to go out of the
  cell
• if the cell membrane were permeable to Na and K
  ions, then Na and K ions would diffuse along
  their electrical and chemical gradients and would
  reach equilibrium
• if the cell was at equilibrium in terms of ion
  concentrations and charge, their would be no
  potential energy available for impulse
  transmission

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Resting Membrane Potential (cont.)

• Neuron Membrane at rest is polarized
• the cytoplasm inside is negatively charged
  relative to the outside
• the net negative charge in the cytoplasm attracts
  all cations to the inside
• some Na leaks in, despite limited membrane
  permeability
• Na-K ATPase keeps working to pump 3 Na ions
  out and 2 K ions in, opposing the two
  concentration gradients (for Na and K)

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Resting Membrane Potential (cont.)

• Here is the electrochemical gradient at rest the
  resting potential

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Membrane Potentials As Signals

• cells use changes in membrane potential (voltage)
  to exchange information
• voltage changes occur by two means
• changing the membrane permeability to an ion or
• changing the ion concentration on either side of
  the membrane
• these changes are made by ion channels
• passive channels leaky K
• active channels
• chemically gated by neurotransmitters
• voltage gated

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Types of Membrane Potentials

• graded potentials
• graded different levels of strength
• dependent on strength of the stimulus
• action potentials
• in response to graded potentials of significant
  strength
• signal over long distances
• all or nothing

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Types of Membrane Potentials

• graded potentials and action potentials may be
  either
• hyperpolarizing
• increasing membrane polarity
• making the inside more negative
• depolarizing
• decreasing membrane polarity
• making the inside less negative more positive

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Graded Potential Propagation

• bidirectional
• ions flow down the membrane
• signal strength dissipates away from the stimulus
  

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More Properties of Graded Potentials

• short lived and transient
• local changes in membrane polarization status
• the size of the voltage change varies with the
  intensity of the stimulus
• stimulus strength decreases with the distance the
  potential travels away from the stimulus
• these are characteristic of
• Receptor potentials
• Postsynaptic potentials
• Endplate potentials

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Properties of Action Potentials

• a nerve impulse (action potential) is generated
  in response to a threshold graded potential
• depolarization
• change in the membrane polarization
• stimuli reach a threshold limit and open
  voltage-gated Na channels
• Na ions rush into the cell ? down the Na
  concentration and electrical gradients
• the cytoplasm inside the cell becomes positive
• reverses membrane potential to 30 mV
• local anesthetics prevent opening of
  voltage-gated Na channels - prevent
  depolarization

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Sequence of Events in Action Potentials

• Resting membrane potential

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Sequence of Events in Action Potentials

• Depolarization
• stimulus strength reaches threshold limit
• voltage gated Na channels open
• Na flows into the cytoplasm
• More V-gated Na channels open
• positive feedback

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Sequence of Events in Action Potentials

• Repolarization
• voltage gated K channels open
• voltage gated Na channels close

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Sequence of Events in Action Potentials

• Hyperpolarization
• gated Na channels are reset to closed
• membrane remains hyperpolarized until K channels
  close, causing the relative refractory period

40
Repeat the process
41
Sequence of Events in Action Potentials

• Resting membrane potential

42
Sequence of Events in Action Potentials

• Depolarization
• stimulus strength reaches threshold limit
• voltage gated Na channels open
• Na flows into the cytoplasm
• More V-gated Na channels open
• positive feedback

43
Sequence of Events in Action Potentials

• Repolarization
• voltage gated K channels open
• voltage gated Na channels close

44
Sequence of Events in Action Potentials

• Hyperpolarization
• gated Na channels are reset to closed
• membrane remains hyperpolarized until K channels
  close, causing the relative refractory period

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The All-or-None Principle

• stimuli/neurotransmitters arrive and open some of
  the chemically-gated Na channels
• if stimuli reach the threshold level ?
  depolarization occurs
• voltage-gated Na channels open
• an Action Potential is generated which is
  constant and at maximum strength
• if stimuli do not reach the threshold level ?
  nothing happens

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Repolarization

• Re-establishing the resting membrane polarization
  state
• threshold depolarization opens Na channels
• Na ions flow inward, making the cell interior
  more positive
• a few milliseconds later, K channels also open
• K channels open more slowly and remain open
  longer
• K ions flow out along its concentration and
  charge gradients
• carries positive () charges out, making the cell
  interior more negative (-)
• Ion movements drive the membrane potential back
  toward resting membrane potential value
• Na/K ATPase continue pumping ions, adjusting
  levels back to resting equilibrium levels
• hyperpolarization briefly the exterior of the
  membrane is more negative than resting potential
  voltage level

47
Refractory Periods
Many physiologists consider this to be the start
of the absolute refractory period

• Absolute Refractory Period
• the time period during which second AP cannot be
  initiated
• due to closure of voltage-gated Na channels
• the voltage-gated Na channels must be reset
  before the membrane can respond to the next
  stimulus

48
Refractory Periods

• Relative Refractory Period
• The time period during which a second AP can be
  initiated with a suprathreshold stimulus
• K channels are open, Na channels are closed
• the membrane is still hyperpolarized

49
Propagation of an Action Potential

• the movement of an Action Potential down an
  unmyelinated axon
• a local electrochemical current, a flow of
  charged ions
• influx of sodium ions
• attraction of positive charges for negative area
  of membrane nearby
• depolarizes nearby membrane opening V-gated Na
  channels

50
Propagation of an Action Potential

• destabilizing the adjacent membrane makes the
  Action Potential self-propagating and
  self-sustaining
• the Action Potential renews itself at each region
  of the membrane a relatively slow process
  because so much is happening at the molecular
  level

51
Conduction Velocity

• physical factors may influence impulse conduction
• heat increases conduction velocity
• cold decreases conduction velocity
• 2 structural modifications can increase impulse
  velocity
• increase neuron diameter - decreases resistance
• insulate the neuron - myelin sheath
• myelinated fibers may conduct as rapidly as 150
  m/sec
• unmyelinated may conduct as slowly as 0.5 m/sec

52
Saltatory Conduction

• not a continuous region to region depolarization
• instead, a jumping depolarization
• myelinated axons transmit an Action Potential
  differently
• the myelin sheath acts as an insulator preventing
  ion flows in and out of the membrane
• neurofibral nodes (node of Ranvier) interrupt the
  myelin sheath and permit ion flows at the exposed
  locations on the axon membrane
• the nodes contain a high density of voltage-gated
  Na channels

53
Saltatory Conduction

• in a myelinated fiber, the ionic current flows in
  at each node and travels through the axoplasm to
  the next node
• each node depolarizes in sequence, renewing the
  Action Potential at that node
• the Action Potential jumps to next node very
  rapidly
• energy efficient the membrane only has to
  depolarize and repolarize at the nodes
• less Na/K ATPase activity is required,
  therefore, less energy is required

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The Synapse

• Function
• there must be a means of communication between
  each neuron and the next target cell
• the synapse is the connection

• Organization
• presynaptic neuron
• postsynaptic neuron
• separated by synaptic cleft

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The Two Types of Synapses

• (1) electrical synapses
• gap junctions found in cardiac muscle and in
  some smooth muscle tissues
• direct, rapid electrochemical connections between
  neurons
• may be bidirectional useful for coordinated
  contraction
• rare in adults
• (2) chemical synapses
• specialized for synthesis, release, reception and
  removal of neurotransmitters
• neurotransmitters
• chemical signal molecules released from a
  presynaptic neuron
• function to open or close chemically-gated ion
  channels
• effect membrane permeability and membrane
  potential

56
Action of a Chemical Synapse

• Presynaptic Events
• an action potential reaches the axon terminal and
  depolarizes the terminal
• voltage gated Ca2 channels open Ca2 ions enter
  the axoplasm
• neurotransmitter is released by exocytosis
• neurotransmitter molecules diffuse across the
  cleft

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Action of a Chemical Synapse (cont.)

• Postsynaptic Events
• the neurotransmitters bind to specific
  postsynapticreceptors
• gated ion channels open as a result
• neurotransmitter molecules are eliminated quickly
• degraded by extracellular enzymes in the synapse,
  with the products re-uptaken and recycled by the
  axon terminal
• diffuse away from the synapse to the blood
  circulation

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Postsynaptic Potentials

• EPSP
• excitatory postsynaptic potential
• provides a small local depolarization
• generally results from opening Na channels
• IPSP
• inhibitory postsynaptic potential
• provides a small local hyperpolarization
• generally results from opening K or CL- channels

59
Summation of Postsynaptic Potentials

• temporal rapid repeated stimulation from 2 or
  more presynaptic neurons
• spatial simultaneous stimulation at 2 or more
  different places on the neuron by presynaptic
  neurons
• EPSPs and IPSPs counteract each other

60
End Chapter 11
61
The Nernst Equation
EX Equilibrium potential of ion X in volts R
gas constant T temperature in kelvins z
charge of each ion F Faradays constant (96,500
coulombs/gram-equivalent charge X ion
concentration
At 38C, (the standard temperature of many
mammals) converting ln
62
The Goldman-Hodgkin-Katz Equation
PERMEABILITY CHANGES DEPENDING UPON NEURON STATUS
At rest PKPNaPCl1/0.04/0.45 At
Action Potential Peak
PKPNaPCl1/20/0.45
EX Equilibrium potential of all ions in volts R
gas constant T temperature in kelvins F
Faradays constant (96,500 coulombs/gram-equivalen
t charge
63
The Goldman-Hodgkin-Katz Equation
At rest PKPNaPCl1/0.04/0.45