Organization of the Nervous System

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Organization of the Nervous System

• Central Nervous System The Brain and Spinal
  Cord
• Peripheral Nervous System
• Sensory or Afferent Branch
• Motor or Efferent Branch
• Autonomic Nervous System actually part of both
  CNS and PNS

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Central Nervous System

• Spinal Cord Brainstem
• Cerebellum Midbrain
• Diencephalon Cerebral
• hemispheres
• Note symmetrical

www.driesen.com/ Brain_View_-1.jpg
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Organization of the Nervous System

• Central Nervous System The Brain and Spinal
  Cord
• Peripheral Nervous System
• Sensory or Afferent Branch
• Motor or Efferent Branch
• Autonomic Nervous System actually part of both
  CNS and PNS

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Cells of the Nervous System

• Neurons
• Structures
• Dendrites
• Cell body - soma
• Axon
• Synaptic terminal
• Glia - come back to these
  

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Synaptic Terminal Classification

• By structure
• a.Multipolar
• b.Bipolar
• c.Unipolar
• By function
• Sensory neuron (afferent neuron)
• Motor neuron (efferent neuron)
• Interneuron

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www.psyweb.com/Physiological/ Neurons/bineuron.htm
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www.psyweb.com/Physiological/ Neurons/multineuron.
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Glial cells

• In CNS  oligodendrocytes, astroglia, microglia 
  and ependymal   cells
• Outnumber neurons in the nervous system 10-501
• Help maintain environment
• Provide physical support
• Some glial cells provide metabolic support to
  neurons and help maintain the composition of the
  extracellular fluid
• Evidence of bidirectional communication between
  glia and neurons
• In PNS Schwann cells, satellite cells

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Glia

• Oligodendroglia (CNS)/Schwann cells (PNS)
• Myelination
• Nodes of Ranvier
• astroglia
• Fibrous astrocyte
• Protoplasmic astrocyte
• Microglia

Figure from Silverthorn Human Physiology
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Peripheral Nervous System

• Afferent- ascending information
• Carries information from periphery to the brain
• sensory
• Efferent- descending information
• Carries information from the brain to the
  periphery
• Somatic voluntary
• Autonomic - involuntary

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CNS
PNS
afferent
efferemt
receptors
autonomic
somatic
parasympathetic
muscles
sympathetic
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Somatic Nervous System (voluntary)

• Controls the contraction of skeletal muscles
• Sensory nerves transmit info from sensory
  receptors to CNS
• Motor nerves transmit instructions to skeletal
  muscles

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Autonomic Nervous System (involuntary)

• Controls contraction and secretion in the various
  internal organs of the body e.g. smooth and
  cardiac muscle, endocrine glands
• Sensory nerves transmit info from internal organs
  or glands to CNS
• Motor nerves transmit instructions to internal
  organs or glands
• Autonomic nervous system further divided into
  sympathetic and  parasympathetic branches which
  function to maintain homeostasis in the body (see
  later)

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Enteric nervous system

• Sometimes thought of as a "third"division of the
  nervous system        
• Network of neurons in wall of digestive tract
• More neurons than in spinal cord
• Frequently under autonomic control but can
  function autonomously

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Parts of the neuron

• Dendrites receive input i.e. antennae
• Soma integrates the information
• Axon hillock initiates the efferemt response
  i.e. action potential when threshold reached

signal
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Types of synapses

• Neuroneuronal
• Axodendritic Axoaxonal
• Axosomatic Dendrodrendritic
• Neuromuscular Motor neuron and skeletal muscle
• Neuroglandular Motor neuron and gland

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Axonal transport
Axonal transport
Diffusion of membrane and cytoplasmic components
to the ends of long axons is too slow. Thus,
have a special transport mechanism called AXONAL
TRANSPORT. Requires ATP , Ca, microtubules,
and neurofilaments
anterograde
retrograde
soma
Axon terminal
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Fast vs slow

• Organelles, synaptic vesicles, etc. moved via
  fast transport 400mm/day
• Proteins etc. Move via slow transport 1 mm/day
• Can be used to determine connections between
  neurons and other cells using dyes.
• Can be used by viruses to cause problems

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Synaptic Terminal

• site of synthesis of low molecular NT
• Location of storage of NT in synaptic vesicles
• Location of transporters for the reuptake of NT
  and their component

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Neurons are electrically excitable cells

• They have across their cell membrane a
  difference in charge (inside vs outside) called
  the membrane potential
• This is set up by the selectively permeable lipid
  bilayer, the Na/K ATPase pump and ion channels
  (voltage and non-voltage gated)

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Voltage-gated ion channelsPotassium
Voltage dependent
Two state Open or closed Selective thought to
be due to geometry of negatively charged amino
acid residues that line the pore.




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Sodium See figure 3-6
Voltage dependent - activation gate
Time dependent - inactivation gate
At rest
Must reset
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Patch Clamp recording

• Nobel in 1991 to Neher and Sakmann
• What is it?
• Channel current measurement made with voltage
  clamp-technique
• What???
• To study individual ion channels, a fire
  polished microelectrode is placed against the
  cell and suction is applied. Thus a
  high-resistance seal is formed and this patch of
  membrane can be used to determine the activity of
  the channels within it.
• Note single channels have specific behaviors
  i.e. open at a particular voltage, however not
  all exhibit the same behavior.

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Resting Membrane Potential

• The assymetric distribution of ions creates
  electrical and chemical gradients.
• These serve as a source of potential energy and
  result in a charge difference across the membrane
  at rest RESTING MEMBRANE POTENTIAL

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Measuring a membrane potential
The extracellular environment is (by convention)
considered to be ground. Thus, it is always 0mv
0 mV
-90
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Measuring a membrane potential
The intracellular environment is negative with
respect to the outside, and is the membrane
potential. Between -60 mV and -90 mV.
0 mV
-90
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Membrane potential (Em)

• Measured as voltage.
• In millivolts mV
• Inside is measured with respect to the outside
  which is 0 mV
• Depolarization is a shift toward more positive
  potentials - associated with excitation
• Hyperpolarization is a shift toward more negative
  potentials - associated with inhibition

time
-
RMV
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Typical ionic concentrations (mM)

• INTERNAL EXTERNAL
• K 100 10
• Na 10 100
• Cl 10 100
• Ca .0001 1

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The Na pump contributes to the resting membrane
potential
E
K
K
ATP
C
Ca
Ca
Na
Na
Cl-
Cl-
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Electrogenic pump contributes to the membrane
potential (Em)

• Na/K ATPase pump contributes 10-20 of Em

V
Resting (Vm)
oubain
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Forces exerted by ions

• Ions have both electrical and chemical forces
• Chemical effects arise from the passive diffusion
  of ions
• Electrical effects arise from the interaction of
  charges with the membrane potential (voltage) the
  magnitude of an ionic gradient depends on both
  concentration and voltage.

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Model

• Purpose
• To illustrate the counterbalancing effects of ion
  gradients
• Cell membrane is semipermeable and a selective
  barrier
• K and Cl- are permeant
• Na and A- (large anions) are impermeant
• At steady state, there is no net ion flow across
  the barrier

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K A-
Na Cl-
At the beginning
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K A-
Na Cl-
Chemical gradient
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Resulting in a charge difference and an
electrical force chemical force
K A-

Na Cl-
- - -
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Cells contain impermeant molecules
Proteins Nucleotides Metabolic byproducts Other
negatively charged particles
A-
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Model differs from real cell

• Require constant activity of Na-K-ATPase pump in
  order to maintain steady state
• External Na is not really impermeant
• A small steady leak occurs through secondary
  transport systems and other pathways.
• Balanced by pumping of Na out of cell

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Points concerning membrane potential

• K and Cl- gradients are in balance near resting
  potential
• Electrochemical gradients can be determine from
  the Nernst equation
• For an ion (X), Ex is the voltage at which the
  electrical and chemical forces are equal and
  opposite thus there is no net flow of X across
  the membrane

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Where does this equation come from?

• Electrical work WE
• WE n z F Ex
• n amount of ion
• z charge
• F constant
• Ex voltage gradient

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• Chemical work WC
• WC n R T ln (Xo/ Xi)
• R and T are constant
• Xo/Xi ratio is the concentration gradient

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Steady state

• WE WC
• n z F Ex n R T ln (Xo/ Xi)
• z F Ex R T ln (Xo/ Xi)
• Ex (R T/ z F) ln (Xo/ Xi)
• R T/ z F 60 mV for a base 10 log

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The Nernst equation

• Ex 60 log (Xo/ Xi)
• For a cation x

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What is the significance of knowing this
equation?????

• At any membrane potential other than the Ex there
  will be a driving force for the movement of X
  across the membrane
• The greater the difference between the membrane
  potential and the Ex will result in a greater
  driving force for net movement of ions.
• Movement can only happen if there are open
  channels!

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Flux (J) a term describing the rate of movement
of solute molecules J - DA x dc/dx D
diffusion coefficient A area through which
diffusion occurs
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Resting membrane potential

• All the ions that the membrane is permeable to
  contribute to the establishment of the potential
  of the membrane at rest
• This can be calculated using the chord
  conductance equation
• Em gk/SgEk gNa/Sg ENa gCl/Sg ECl
• Sg (gk gNa gCl)
• What is g??? The conductance of the membrane to
  the ions reciprocal of resistance
• E equilibrium potential of the ion

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• In words this equation means that the membrane
  potential is a weighted average of the
  equilibrium potentials of all the ions to which
  the membrane is permeable. The average is
  weighted by the ions conductance (determined by
  open channels)
• So as the weighting of one ion increases that of
  the others decreases.

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Role of Na/K ATPase

• The pump transfers 3 Na for every 2 K. So there
  is a net transfer of charge across the membrane
  as a result.
• Thus, the pump contributes directly to Em
• Only a small part of electrically active cells
• Major portion of Em is due to diffusion of Na and
  K down their gradients.
• Thus, the pump contributes more indirectly by
  maintaining these gradients.

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GENERATION OF ACTION POTENTIALS

• Resting membrane potential characteristic
  feature of ALL cells in the bodyExcitable cells
  can alter these potentials for the purpose of
  communication (nerve cells) or the initiation of
  muscle contraction (muscle cells)Two types of
  electrical signal can be generated by excitable
  cells graded potentials and action potentials

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ACTION POTENTIAL
Measured as a transient change in Em Used to
conduct information within a cell Regenerative
event that requires only a threshold
(non-regenerative or graded potential)
depolarization to start All-or-none event
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Graded Potentials

• (Fig. 8-8 Silverthorn)The size (amplitude) of
  the graded potential is directly proportional to
  the strength of the triggering event. A strong
  stimulus will produce a large graded potential, a
  weak stimulus will produce a small graded
  potential.A graded potential can be either
  hyperpolarizing (make membrane potential more
  negative) or depolarizing (make membrane
  potential more positive)Graded potentials
  decrease in strength as they spread from their
  point of origin

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Action Potentials

• Action potentials arise as a result of brief
  alterations in the electrical properties of the
  membraneAction potentials are all or nothing
• Action potentials differ in size and shape but
  the fundamental mechanisms underlying the
  initiation of these potentials does not
  varyAction potentials are very brief events
  (1msec)The intensity of a stimulus is encoded
  by the frequency of action potentials

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Ionic Basis of Action Potentials

• At rest - membrane highly permeable to K ions and
  slightly permeable to Na. and Cl ions
• Ions move into and out of the cells through
  passive K and Na channels.
• If nerve cell is activated (i.e. cell becomes
  more depolarized) membrane permeability
  switches.
• It becomes highly permeable to Na ions via
  opening of voltage gated Na channels.

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Sequence of events underlying generation of
Action Potential
Initiation and rising phase of action potential
8-9
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• Activation of nerve cell depolarization of
  membrane potential (potential becomes more
  ive).Membrane depolarized to sufficient level
  and fast voltage gated Na channels open in the
  membrane.Na ions rush into cell along
  concentration and electrical gradient.Cell
  becomes more depolarized more Na channels open,
  more Na ions enter cell, cell becomes more
  depolarizedAt peak of action potential membrane
  potential approaches ENa

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Repolarization phase

• Voltage dependent Na channel inactivated.Slow
  voltage dependent K channels also open in the
  membrane in response to the depolarization K
  moves out of the cell (along both chemical and
  electrical gradients) and the cell becomes
  hyperpolarized. The membrane potential
  approaches Ek

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Afterhyperpolarization

• Membrane potential actually becomes less negative
  than it is at rest (the afterhyperpolarization).
  Voltage dependent K channels close slowly. They
  are still open during the afterhyperpolarization
  thus in addition to the passive resting K
  channels (that contribute to the resting membrane
  potential) there are also voltage dependent K
  open at the same time. The membrane potential
  dips down lower than it would at the resting
  potential because of the two populations of K
  channels open (voltage dependent and also passive
  channels). Eventually the voltage dependent K
  channels close and the membrane potential reaches
  the resting membrane potential again (only
  passive K channels are contributing to the
  membrane potential.

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• Why do voltage dependent Na channels close during
  depolarization?

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Silverthorn
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8-10a-e Silverthorn
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Refractory Period Fig

• Divided into absolute and relative refractory
  periods.
• Absolute refractory period
• Lasts about 0.5 -1 msec after the peak of the
  action potential has been initiated. During
  this time period it is impossible to initiate
  another action potential. It takes a time for
  the Na channels to recover from inactivation.
  The absolute refractory period ensures that a
  second action potential will not be initiated
  before the first has finished.

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Relative refractory period

• A higher than normal amount of depolarization (a
  larger stimulus) is required to trigger an action
  potential. Occurs during the afterhyperpolarizat
  ion phase of the action potential. During the
  afterhyperpolarization the voltage dependent K
  channels are still open and the movement of K out
  of the cell is going to offset the depolarization
  produced by movement of Na through voltage gated
  Na channels. Also not all of the Na channels
  have been reset since inactivation occurred.