Neurophysiology:The Generation, Transmission, and Integration of Neural Signals

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NeurophysiologyThe Generation, Transmission, and
Integration of Neural Signals
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3 Neurophysiology The Generation, Transmission,
and Integration of Neural Signals

• Electrical Signals are the Vocabulary of the
  Nervous System
• The Sequence of Transmission Processes at
  Chemical Synapses
• Neurons and Synapses Combine to Make Circuits
• Gross Electrical Activity of the Human Brain

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3 Electrical Signals Are the Vocabulary of the
Nervous System

• A neuron at rest is a balance of electrochemical
  forces.
• Ions electrically charged molecules, anions are
  negatively charged and cations are positively
  charged
• Ions are dissolved in intracellular fluid,
  separated from the extracellular fluid by the
  cell membrane.

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3 Electrical Signals Are the Vocabulary of the
Nervous System

• A microelectrode inserted into a resting cell
  shows that it is more negative than the
  extracellular fluid.
• The resting membrane potential is 50 to 80
  millivolts (mV) and shows the negative polarity
  of the cells interior.

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Figure 3.1 Measuring the Resting Potential
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• The cell membrane is a lipid bilayer, with two
  layers of lipid molecules.
• Ion channels are proteins that span the membrane
  and allow ions to pass
• gated channels open and close in response to
  voltage changes, chemicals, or mechanical action
  

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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Some channels are open all the time and allow
  only potassium ions (K) to cross.
• The neuron shows selective permeability to (K)
  it can enter or leave the cell freely.

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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Two opposing forces drive ion movement
• Diffusion causes ions to flow from areas of high
  to low concentration, along their concentration
  gradient.
• Electrostatic pressure causes ions to flow
  towards oppositely charged areas.

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Figure 3.2 Ionic Forces Underlying Electrical
Signaling in Neurons
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• At rest, K ions move into the negative interior
  of the cell because of electrostatic pressure.
• As K ions build up inside the cell, they also
  diffuse out along the concentration gradient.

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3 Electrical Signals Are the Vocabulary of the
Nervous System

• K reaches equilibrium when the movement out is
  balanced by the movement in.
• This corresponds to the resting membrane
  potential of about 60 mV.

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Figure 3.3 The Ionic Basis of the Resting
Potential (Part 1)
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• The Nernst equation describes the voltage
  produced when a membrane separates different
  concentrations of ions.
• The membrane is also slightly permeable to sodium
  ions (Na) and ions leak in.
• The sodium potassium pump pumps Na out and K
  in, to maintain the resting potential.

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Figure 3.3 The Ionic Basis of the Resting
Potential (Part 2)
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Figure 3.4 The Distribution of Ions Inside and
Outside of a Neuron
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Action potentials, or nerve impulses, are brief
  but large changes in membrane potential.
• They originate in the axon hillock and are
  propagated along the axon.
• Patterns of action potentials carry information
  to postsynaptic targets.

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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Hyperpolarization is an increase in membrane
  potential, caused by inhibitory messages, which
  puts it farther away from zero.
• Depolarization is a decrease in membrane
  potential caused by excitatory messages, bringing
  it closer to zero.

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3 Electrical Signals Are the Vocabulary of the
Nervous System

• A graded response is a postsynaptic change in
  electrical potential that spreads passively
  across the membrane, and decreases over time and
  distance.
• A hyperpolarizing stimulus produces a response
  that has the same shape as the stimulus
• The greater the stimulus the greater the response

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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Local potentials - also called graded or
  postsynaptic potentials
• As a local potential spreads across the membrane,
  it diminishes as it moves away from the point of
  stimulation.

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Figure 3.5 The Effects of Hyperpolarizing and
Depolarizing Stimuli on a Neuron (Part 1)
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• A depolarizing stimulus is the same as a
  hyperpolarizing one, to a point.
• If the membrane reaches the threshold about 40
  mV it triggers an action potential.
• The membrane potential reverses and the inside of
  the cell becomes positive.

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Figure 3.5 The Effects of Hyperpolarizing and
Depolarizing Stimuli on a Neuron (Part 2)
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• All-or-none property of action potentials the
  neuron fires at full amplitude or not at all
  does not reflect increased stimulus strength
• Action potentials increase frequency with
  increased stimulus strength.
• Afterpotentials follow action potentials

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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Action potentials are produced by the movement of
  Na ions into the cell.
• At the peak the concentration gradient pushing
  Na ions in equals the positive charge driving
  them out.
• Membrane shifts briefly from a resting state to
  an active state, and back.

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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Voltage-gated Na channels open in response to
  the initial depolarization.
• More voltage-gated channels open and more Na
  ions enter.
• This continues until the membrane potential
  reaches the Na equilibrium potential of 40 mV.

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3 Electrical Signals Are the Vocabulary of the
Nervous System

• As the inside of the cell becomes more positive,
  voltage-gated K channels open.
• K moves out and the resting potential is
  restored.

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Figure 3.6 Mediation of the Action Potential by
Voltage-Gated Sodium Channels
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Refractory period only some stimuli can produce
  an action potential
• Absolute refractory phase no action potentials
  are produced
• Relative refractory phase only strong
  stimulation can produce an action potential

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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Ion channels are very specific in their function
  K channels are lined with oxygen atoms that
  mimic water molecules.
• K ions pass through this selectivity filter more
  easily than Na
• Channelopathy genetic abnormality of ion
  channels

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Box 3.1 (A) Changing the Channel
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Animal toxins selectively block certain channels
• Tetrodotoxin (TTX) and saxitoxin (STX) block
  voltage-gated Na channels.
• Batrachotoxin forces Na channels to stay open.

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Box 3.1 (B) Changing the Channel
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Action potentials are regenerated along the axon
  each adjacent section is depolarized and a new
  action potential occurs.
• Action potentials travel in one direction because
  of the refractory state of the membrane after a
  depolarization.

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Figure 3.7 Propagation of the Action Potential
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Conduction velocity the speed of action
  potentials varies with diameter
• Nodes of Ranvier small gaps in the insulating
  myelin sheath
• Saltatory conduction the axon potential travels
  inside the axon and jumps from node to node

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Figure 3.8 Conduction along Unmyelinated versus
Myelinated Axons (Part 1)
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Figure 3.8 Conduction along Unmyelinated versus
Myelinated Axons (Part 2)
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Synapses cause local changes in postsynaptic
  membrane potentials, through neurotransmitters.
• Besides chemical synapses there are electrical
  synapses, or gap junctions. Ions flow directly
  through large channels into adjacent cells, with
  no time delay.

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Box 3.2 (A) Electrical Synapses Work with No
Time Delay
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Box 3.2 (B) Electrical Synapses Work with No
Time Delay
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Postsynaptic potentials are brief changes in the
  resting potential.
• Excitatory postsynaptic potential (EPSP)
  produces a small local depolarization, pushing
  the cell closer to threshold
• Synaptic delay the delay between an action
  potential reaching the axon terminal and creating
  a postsynaptic potential

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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Inhibitory postsynaptic potential (IPSP)
  produces a small hyperpolarization, pushing the
  cell further away from threshold
• IPSPs result from chloride ions (Cl-) entering
  the cell, making the inside more negative.

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Figure 3.9 Recording Postsynaptic Potentials
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Neurons perform information processing to
  integrate synaptic inputs.
• A postsynaptic neuron will fire an action
  potential if a depolarization that exceeds
  threshold reaches its axon hillock.

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Figure 3.10 Spatial Summation in a Postsynaptic
Cell (Part 1)
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Figure 3.10 Spatial Summation in a Postsynaptic
Cell (Part 2)
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Spatial summation is the summing of potentials
  that come from different parts of the cell.
• If the overall sum of EPSPs and IPSPs can
  depolarize the cell at the axon hillock, an
  action potential will occur.

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Figure 3.10 Spatial Summation in a Postsynaptic
Cell (Part 3)
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3 Electrical Signals Are the Vocabulary of the
Nervous System

• Temporal summation is the summing of potentials
  that arrive at the axon hillock at different
  times.
• The closer together in time that they arrive, the
  greater the summation and possibility of an
  action potential.

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3 The Sequence of Transmission Processes at
Chemical Synapses

• The sequence of transmission
• Action potential travels down the axon to the
  axon terminal.
• Voltage-gated calcium channels open and calcium
  ions (Ca2) enter.
• Synaptic vesicles fuse with membrane and release
  transmitter into the cleft.

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3 The Sequence of Transmission Processes at
Chemical Synapses

1. Transmitters bind to postsynaptic receptors
   cause an EPSP or IPSP.
2. EPSPs or IPSPs spread toward the postsynaptic
   axon hillock.
3. Transmitter is inactivated or removed action is
   brief.
4. Transmitter may be bound by presynaptic
   autoreceptors, decreasing release.

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Figure 3.11 Steps in Transmission at a Chemical
Synapse
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3 The Sequence of Transmission Processes at
Chemical Synapses

• An action potential causes Ca2 channels to open
  in the axon terminal and allow Ca2 into the
  cell.
• Ca2 causes synaptic vesicles to fuse with the
  presynaptic membrane and release neurotransmitter
  into the cleft.

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3 The Sequence of Transmission Processes at
Chemical Synapses

• Ligands fit receptors and activate or block them
• Endogenous ligands neurotransmitters and
  hormones
• Exogenous ligands drugs and toxins from outside
  the body

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3 The Sequence of Transmission Processes at
Chemical Synapses

• A synapse that uses acetylcholine (ACh) has
  recognition sites for ACh within the receptor
  molecules in the postsynaptic membrane.
• ACh can be excitatory, and open channels for Na
  and K, or inhibitory, and open channels for Cl-.

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Figure 3.12 A Nicotinic Acetylcholine Receptor
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3 The Sequence of Transmission Processes at
Chemical Synapses

• Some chemicals can fit on cholinergic receptors
  and block the action of ACh
• Curare and bungarotoxin block ACh receptors are
  antagonists
• However, muscarine and nicotine mimic ACh and are
  agonists of the receptor.

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3 The Sequence of Transmission Processes at
Chemical Synapses

• The number of receptors in cells can vary (in
  plasticity) daily in adulthood - also during
  development or with drug use.
• Up-regulation is an increase in the number of
  receptors, and down-regulation is a decrease.

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3 The Sequence of Transmission Processes at
Chemical Synapses

• Receptors control ion channels in two ways
• Ionotropic receptors open when bound by a
  transmitter (also called a ligand-gated ion
  channel).
• Metabotropic receptors recognize the transmitter
  but instead activate G proteins.

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Figure 3.13 Two Types of Chemical Synapses (Part
1)
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3 The Sequence of Transmission Processes at
Chemical Synapses

• G proteins, or first messengers, sometimes open
  channels or may activate another chemical to
  affect ion channels.
• The chemical is known as the second messenger
  it amplifies the effects of the G protein and may
  lead to changes in membrane potential.

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Figure 3.13 Two Types of Chemical Synapses (Part
2)
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3 The Sequence of Transmission Processes at
Chemical Synapses

• Transmitter action is brief
• Degradation is the rapid breakdown and
  inactivation of transmitter by an enzyme.
• Example acetylcholinesterase (AChE) breaks down
  ACh and recycles it

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3 The Sequence of Transmission Processes at
Chemical Synapses

• Reuptake transmitter is taken up into the
  presynaptic cell
• Pinocytosis is the process of repackaging
  transmitter into vesicles.
• Transporters are special presynaptic receptors
  involved in reuptake.

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3 The Sequence of Transmission Processes at
Chemical Synapses

• Types of synapses
• Axo-dendritic axon terminal synapses on a
  dendrite
• Axo-axonic - between two axons
• Dendro-dendritic between two dendrites
• Retrograde uses gas to signal presynaptic cell
  to release transmitter

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3 The Sequence of Transmission Processes at
Chemical Synapses

• Ectopic transmission occurs outside of
  conventional synapses.
• Varicosities are axonal swellings where
  transmitter may diffuse out.
• These nondirected synapses release transmitter
  steadily to broad areas.

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3 Neurons and Synapses Combine to Make Circuits

• A neural chain is a simple series of neurons.
• The knee jerk reflex is a circuit for the stretch
  reflex, consisting of
• Sensory neuron
• Motor neuron
• Synapse

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3 Neurons and Synapses Combine to Make Circuits

• The knee jerk reflex is extremely fast
• Axons are myelinated and large
• Sensory cells synapse directly onto motoneurons
• Uses fast, ionotropic synapses

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Figure 3.14 The Knee Jerk Reflex (Part 1)
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Figure 3.14 The Knee Jerk Reflex (Part 2)
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3 Neurons and Synapses Combine to Make Circuits

• The visual system is a circuit with other
  features
• Convergence many cells send signals to one cell
• Divergence one cell send signals to many cells
• Units are arranged in parallel, and have lateral
  interaction across units.

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Figure 3.15 Two Representations of Neural
Circuitry (Part 1)
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Figure 3.15 Two Representations of Neural
Circuitry (Part 2)
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3 Gross Electrical Activity of the Human Brain

• An encephalogram (EEG) is a recording of brain
  potentials, or brain waves.
• Brain potentials indicate sleep states and
  provide data in seizure disorders.

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Figure 3.16 Gross Potentials of the Human
Nervous System (Part 1)
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3 Gross Electrical Activity of the Human Brain

• In the normal brain, activity tends to be
  desynchronized across regions.
• A symptom of epilepsy is seizure a
  synchronization of electrical activity in the
  brain.
• The brain wave pattern during seizure is
  described as epileptiform activity.

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3 Gross Electrical Activity of the Human Brain

• Categories of seizures
• Grand mal abnormal activity throughout the
  brain
• Characteristic movements are tonic and clonic
  contractions.
• Seizure is followed by confusion and sleep.

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Box 3.3 (A) Seizure Disorders
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3 Gross Electrical Activity of the Human Brain

• Petit mal seizure brain waves show patterns of
  seizure activity for 5 to 15 seconds, can be
  several times a day
• No unusual muscle activity, except for stopping
  and staring
• Events during seizure are not remembered.

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Box 3.3 (B) Seizure Disorders
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3 Gross Electrical Activity of the Human Brain

• Complex partial seizures do not involve entire
  brain
• Aura unusual sensation that may precede a
  seizure
• Kindling experimentally inducing a seizure by
  repeatedly stimulating a brain region

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Box 3.3 (C) Seizure Disorders
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3 Gross Electrical Activity of the Human Brain

• Event-related potentials (ERPs) are large
  potential shifts caused by discrete stimuli.
• Auditory-evoked brainstem potentials are
  generated in the brainstem, far from the
  recording site can be used to detect hearing
  impairment.

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Figure 3.16 Gross Potentials of the Human
Nervous System (Part 2)