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PowerPoint® Lecture Slides
prepared by
Janice Meeking,
Mount Royal College
CHAPTER
11
Fundamentals of
the Nervous
System and
Nervous Tissue:
Part A
Copyright © 2010 Pearson Education, Inc.
Neurophysiology
• Neurons are highly irritable (responsive to stimuli)
• Action potentials, or nerve impulses, are:
• Electrical impulses carried along the length of
axons
• Always the same regardless the source or type of
stimulus
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Basic principals of electricity
• The human body is electrically neutral (same number of
positive and negative charges)
• There are areas that are either negatively or positively
charged.
• Opposite charges attract each other
• Energy is required to separate opposite charges across a
membrane
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Electricity Definitions
• Voltage (V) – measure of potential energy generated by
separated charge
• Voltage is always measured between 2 points and it is
called – potential difference or potential
• The greater the difference between the 2 points the higher
the voltage
• Current (I) – the flow of electrical charge between two points
• This flow of electrical charges can be used to perform work
(ex. light)
• Resistance (R) – a material's opposition to the flow of electric
current
• Insulator – substance with high electrical resistance
• Conductor – substance with low electrical resistance
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Electrical Current and the Body
• Reflects the flow of ions rather than electrons
• There is a potential on either side of membranes when:
• The number of ions is different across the
membrane
• The membrane provides a resistance to ion flow
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Membrane ion channels
• Ion channels – membrane proteins
• Large with several sub-units
• Sometimes part of the molecule forms a “gate” that
changes the shape to open and close the channel
http://hebb.mit.edu/courses/8.515/lecture1/img013.jpg
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Types of plasma membrane ion channels
• Passive, or leakage, non gated channels – always open
• Gated channels
• Chemically gated / ligand gated channels – open with
binding of a specific chemical (neurotransmitter in case of
the nervous tissue)
• Voltage-gated channels – open and close in response to
membrane potential
• Mechanically gated channels – open and close in response
to physical deformation of receptors
• Each type of channel is selective – only a certain ion/ions are
allowed to pass
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Gated Channels
• When gated channels are open:
• Ions move quickly across the membrane
• Movement is follows their electrochemical gradients
• Ions move along chemical concentration gradient
– from high concentration to a low one
• Ions move along electrical gradient – towards an
area of opposite electrical charge
• An electrical current is created
• Voltage changes across the membrane
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Resting Membrane Potential (Vr)
• The potential difference (–70 mV) across the membrane of
a resting neuron – membrane is polarized
• Minus sign indicates that the inside of the membrane is
negatively charged compared to the outside
• The value can be different in different cells (-40 - -90mv)
• It is generated by different concentrations of Na+, K+, Cl,
and protein anions (A)
• RMP exists only across the membrane – the bulk solutions
in the cell are neutral
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Resting Membrane Potential
• Differential permeability of membrane
• Impermeable to A–
• Slightly permeable to Na+ (through leakage channels)
• 75 times more permeable to K+ (more leakage
channels)
• Freely permeable to Cl–
• The reason there is no equilibrium in the ion concentration
is because of ATP-driven Na+ - K+ pump that ejects 3 Na+
out of the cell and 2 K+ into the cell
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Resting Membrane Potential (Vr)
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Figure 11.8
Changes in Membrane Potential
• Changes are caused by three events – all relative to
RMP
• Depolarization – the inside of the membrane
becomes less negative
• Repolarization – the membrane returns to its
resting membrane potential
• Hyperpolarization – the inside of the membrane
becomes more negative than the resting potential
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Membrane Potentials: Signals
• Used to integrate, send, and receive information
• Membrane potential changes are produced by:
• Changes in membrane permeability to ions
• Alterations of ion concentrations across the
membrane
• Types of signals
• graded potentials – incoming signals over short
distance
• action potentials – long-distance signals
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Graded Potentials
• Short-lived, local changes in membrane potential
• Decrease in intensity with distance
• Magnitude varies directly with the strength of the
stimulus
• the stronger the stimulus, the more voltage changes
and farther the current flows
• Sufficiently strong graded potentials can initiate
action potentials
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Graded Potentials
• A small area of the neuron membrane has been
depolarized by a stimulus (can be electrical, chemical,
mechanical etc.)
• Current will flow on both sides of the membrane –
positive ions will move toward negative ones and vice
versa.
• Most of the charge is lost through leakage channels
• That makes the current decremental – dies out with
increasing distance
• Only travel over short distances
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Action Potentials (APs)
• When a neuron is adequately stimulated, its membrane
permeability changes by opening voltage-gated
channels.
• There is a transition from graded potential (incoming
message) to action potential
• This transition usually occurs in the axon hillock
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Action Potentials (APs)
• The way to send signals over a long distance
• Action potentials are only generated by muscle cells and
neurons (have excitable membrane)
• The AP is a brief reversal of membrane potential with a
total amplitude of 100 mV (from -70- mv to +30)
• They do not decrease in strength over distance
• An action potential in the axon of a neuron is a nerve
impulse
• Very short event – few milliseconds
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Action Potential: Resting State
• Na+ and K+ voltage-gated channels are closed
• Open leakage channels (passive) accounts for small movements of
Na+ and K+
• Each Na+ channel has two voltage-regulated gates (See figure
11.11 p 400-401 in book)
• Activation gates (fast)
• closed in the resting state
• Respond to depolarization by opening
• Inactivation gates (slow)
• open in the resting state
• Blocks the channel while it is open
• Depolarization opens and than deactivates sodium channel
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Action Potential: Depolarization Phase
• Axon membrane is depolarized by local current which
results in the opening of sodium channels
• At this point - Na+ gates are opened; K+ gates are closed
• Na+ enters the cell (influx)
• The influx changes the charge inside causing more Na+
channels to open
• The interior of the membrane becomes less negative until
it reaches the threshold
• Threshold – a critical level of depolarization (-55 to
-50 mV)
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Threshold
• Subthreshold stimulus —weak local depolarization
that does not reach threshold
• Threshold stimulus —strong enough to push the
membrane potential toward and beyond threshold
• AP is an all-or-none phenomenon —action potentials
either happen completely, or not at all
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Action Potential: Depolarization Phase
• At threshold, depolarization becomes self-generating
• After being initiated by the stimulus, depolarization is
driven by the Na+ influx:
• More Na+ enters more channels are open until all
are
• Na+ permeability at this point is 1000 higher than
in resting
• That result in changing the negative internal
environment to a positive one of +30mv
• Sharp action potential
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Action Potential: Repolarization Phase
• The rising phase of AP persist for about 1ms.
• Than, the slow sodium inactivation gates close
• Membrane permeability to Na+ declines to resting levels
• Net influx of sodium stops completely
• AP spike stop rising
• As sodium gates become inactive, slow voltage-sensitive
K+ gates open
• K+ exits the cell and internal negativity of the resting
neuron is restored
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Action Potential: Hyperpolarization
• Potassium gates remain open, causing an excessive
efflux of K+
• This efflux causes hyperpolarization of the membrane
• The neuron is insensitive
depolarization during this time
to
stimulus
and
• Sodium channels start to reset – opening the
inactivation channels and closing the activation gates
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Action Potential: Role of the Sodium-Potassium Pump
• Repolarization restores the resting electrical conditions
of the neuron
• Does not restore the resting ionic conditions
• Ionic redistribution back to resting conditions is
restored by the sodium-potassium pump (what type of
transport mechanism?)
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Propagation of an Action Potential
• Na+ influx causes an area of the axonal membrane to
depolarize
• Local currents occur
• Na+ channels toward the point of origin are inactivated and
not affected by the local currents
• Local currents affect adjacent areas in the forward direction
• Depolarization opens voltage-gated channels and triggers an
AP
• Repolarization wave follows the depolarization wave
• (Fig. 11.12 shows the propagation process in
unmyelinated axons.)
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Coding for Stimulus Intensity
• All action potentials are alike and are independent of
stimulus intensity
• Strong stimuli can generate an action potential more
often in a given time than weaker stimuli
• The CNS determines stimulus intensity by the
frequency of impulse transmission
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Absolute Refractory Period
• When the sodium channels are open, the neuron can not
respond to another stimulus, no matter how strong it is
• Time from the opening of the Na+ activation gates until the
closing of inactivation gates
• The absolute refractory period:
• Prevents the neuron from generating an action potential
• Ensures that each action potential is separate (why is that
important?)
• Enforces one-way transmission of nerve impulses
PLAY
InterActive Physiology ®:
Nervous System I: The Action Potential, page 14
Copyright © 2010 Pearson Education, Inc.
Relative Refractory Period
• During this period the axon threshold is elevated –
(what does that mean?)
• The interval following the absolute refractory period
when:
• Sodium gates are closed
• Potassium gates are open
• Repolarization is occurring
PLAY
InterActive Physiology ®:
Nervous System I: The Action Potential, page 15
Copyright © 2010 Pearson Education, Inc.
Conduction Velocities of Axons
• Conduction velocities vary widely among neurons
• Rate of impulse propagation is determined by:
• Axon diameter – the larger the diameter, the faster the
impulse (effect less dramatic than myelination)
• Larger diameter fibers have less resistance to local
current flow and have faster impulse conduction
• Presence of a myelin sheath – myelination
dramatically increases impulse speed (will be
discussed later)
PLAY
InterActive Physiology ®:
Nervous System I: Action Potential, page 17
Copyright © 2010 Pearson Education, Inc.
Axons types
• Axons are classified into 3 groups according to their relationships
among the diameter, myelination and propagations speed:
• Type A – largest axons and myelinated. Speed is up to
150meters/second (~300mph!!!)
• Carry information about position, balance, touch and pressure
sensation to the CNS
• Motor neurons that control skeletal muscle movement
• Type B and C are autonomic fibers
• Type B – smaller myelinated with an average propagation speed
of 15m/s (30 mph)
• Type C – unmyelinated with propagation speed of 1m/s (2 mph)
• Type B and C carry information about temperature, pain and
general touch sensations to the CNS
• Carry motor signals to smooth and cardiac muscles and glands
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Saltatory Conduction (saltare – to leap)
• Current passes through a myelinated axon only at the
nodes of Ranvier
• Voltage-gated Na+ channels are concentrated at these
nodes
• Action potentials are triggered only at the nodes and
jump from one node to the next
• Much faster than conduction along unmyelinated
axons
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http://fourier.eng.hmc.edu/e180/handouts/figures/actionpotentialtransmission.gif
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Multiple Sclerosis (MS)
• An autoimmune disease that mainly affects young adults
• Symptoms: visual disturbances, weakness, loss of muscular
control, speech disturbances, and urinary incontinence
• Myelin sheaths in the CNS gradually destroyed
• Shunting and short-circuiting of nerve impulses occurs
• Impulse conduction slows and eventually ceases
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Synapses
• A junction that mediates information transfer from one
neuron:
• To another neuron
• To an effector cell
• Presynaptic neuron – conducts impulses toward the
synapse – information sender
• Postsynaptic neuron – transmits impulses away from
the synapse – information receiver
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Electrical Synapses
• Are less common than chemical synapses
• Correspond to gap junctions found in other cell types
• Contain protein channels that connect the cells and allow
ions and small molecules to flow from one cell to the
other.
• Neurons that are joined together with electrical synapse
are called - electrically coupled
• Transmission is fast
• Ability to synchronize several neurons together
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Electrical Synapses
• More abundant in the embryo than in the adult (when
neurons form connection with one another)
• Some electrical synapse in the embryo are replaced
with chemical ones in the adult
• Have a role in the CNS in:
• Arousal from sleep
• Mental attention
• Emotions and memory
• Ion and water homeostasis
PLAY
Copyright © 2010 Pearson Education, Inc.
InterActive Physiology ®:
Nervous System II: Anatomy Review, page 6
Chemical Synapses
• Specialized for the release
neurotransmitters (NT)
and
reception
of
• Typically composed of two parts:
• Axonal terminal of the presynaptic neuron, which
contains synaptic vesicles (containing the NT)
• Receptor region on the dendrite(s) or soma of the
postsynaptic neuron
PLAY
InterActive Physiology ®:
Nervous System II: Anatomy Review, page 7
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Synaptic Cleft
• Fluid-filled space separating the presynaptic and
postsynaptic neurons (30-50 nm wide)
• Prevents nerve impulses from directly passing from
one neuron to the next
• Transmission across the synaptic cleft:
• Is a chemical event (as opposed to an electrical
one)
• Ensures unidirectional communication between
neurons (why?)
PLAY
InterActive Physiology ®:
Nervous System II: Anatomy Review, page 8
Copyright © 2010 Pearson Education, Inc.
Synaptic Cleft: Information Transfer
• Nerve impulses reach the axonal terminal of the presynaptic neuron and
open voltage-gated Ca2+ channels
• Ca2+ enters the axonal terminal from the interstitial fluid.
• The Ca2+ acts as intracellular messenger and promote the fusion of the
vesicles with the axon membrane
• Neurotransmitter is released into the synaptic cleft via exocytosis in
response to synaptotagmin (a Ca binding protein in the vescicle that
might be part of exocytosis process)
• Ca2+ is either taken by the mitochondria or ejected by active Ca2+ pump
(the trigger to this is unknown)
• Neurotransmitter crosses the synaptic cleft and binds to receptors on
the postsynaptic neuron
• Postsynaptic membrane permeability changes (channels are open –
chemically-gated channels), causing an excitatory or inhibitory effect
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Termination of Neurotransmitter Effects
• As long as the NT is bound to the postsynaptic receptor it:
• Produces a continuous postsynaptic effect on permeability
• Blocks reception of additional “messages”
• They must be removed from its receptor
• Removal of neurotransmitters occurs when they:
• Are degraded by enzymes on the postsynaptic membrane or in
the synapse
• Are reabsorbed by astrocytes or the presynaptic terminals
• Diffuse away from the synaptic cleft
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Postsynaptic Potentials
• Receptors on the postsynaptic specialized in opening
chemical-gated channels
• These channels are relatively insensitive to changes in
the membrane potential
• That results in the inability of these channels to
become self-generating
• Neurotransmitter receptor generate graded potential
that depends on the amount of NT released
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Postsynaptic Potentials
• Neurotransmitter receptors mediate
membrane potential according to:
changes
in
• The amount of neurotransmitter released
• The amount of time the neurotransmitter is bound
to receptors
• The two types of postsynaptic potentials are:
• EPSP – excitatory postsynaptic potentials
• IPSP – inhibitory postsynaptic potentials
PLAY
InterActive Physiology ®:
Nervous System II: Synaptic Transmission, pages 7–12
Copyright © 2010 Pearson Education, Inc.
Excitatory Postsynaptic Potentials
• EPSPs are graded potentials that can initiate an action
potential in an axon
• Use a single type of chemically-gated ion channels that
allows Na+ and K+ flow in opposite directions at the same
time
• Electrochemical gradient for sodium is much steeper than
that for potassium
• Sodium influx is greater than potassium efflux
• That will result in increased sodium concentration inside
and depolarization
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Excitatory Postsynaptic Potentials
• If enough NT are bound to the postsynaptic receptors,
depolarization can reach 0 mV which is beyond axon
threshold (-50mV)
• Postsynaptic membranes do not generate action
potentials but its role is to generate EPSP that will
trigger AP distally at the axon hillock.
• EPSP often travel all the way to the axon hillock
(although decline with distance)
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Inhibitory Synapses and IPSPs
• Neurotransmitter binding to a receptor at inhibitory
synapses:
• Causes the membrane to become more permeable
to potassium and chloride ions (causing
hyperpolarization)
• Leaves the charge on the inner surface negative
• Reduces the postsynaptic neuron’s ability to
produce an action potential
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Integration: Summation
• A single EPSP cannot induce an action potential
• EPSPs can summate to reach threshold
• IPSPs can also summate with EPSPs, canceling each
other out
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Integration: Summation
• Temporal summation
• One or more presynaptic neurons transmit impulses in rapidfire order
• presynaptic neurons transmit impulses in rapid-fire order
• first impulse produce small EPSP and the second arrives
before the first disappears
• Spatial summation
• Postsynaptic neuron is stimulated by a large number of
terminals at the same time
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Summation
• IPSPs can also summate both temporally and spatially
• Most neuron receive both excitatory and inhibitory inputs
from thousands of other neurons
• The axon hillock of the neuron keeps “records” of all
signals – act as neural integrators
• EPSP summate with IPSP and depending on who
dominate, that will be the effect on the cell.
• Partially depolarized neurons are said to be facilitated –
more easily depolarized by the next stimulus
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Copyright © 2010 Pearson Education, Inc.
Table 11.1.1
Neurotransmitters
• The way neurons communicate with post-synaptic
cells.
• NT are considered paracrine agents
• Most neurons make two or more neurotransmitters,
which are released at different stimulation frequencies
• 50 or more neurotransmitters have been identified
• Classified by chemical structure and by function
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Chemical Neurotransmitters
• Acetylcholine (ACh) – neuro-muscular junction, ANS
• Biogenic amines – substance produced by life
processes. It may be either constituents, or secretions,
of plants or animals (coal, oil, pearls etc).
• Example Catecholamines – dopamine,
norepinephrine (NE), and epinephrine
• Amino acids - GABA – Gamma ()-aminobutyric acid,
Glycine, Aspartate, Glutamate (only in CNS)
• Peptides
• Novel messengers: ATP and dissolved gases NO and
CO
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Functional Classification of
Neurotransmitters
• Two classifications: excitatory and inhibitory
• Excitatory neurotransmitters cause depolarizations
(e.g., glutamate)
• Inhibitory neurotransmitters cause
hyperpolarizations (e.g., GABA and glycine)
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One NT – more than one receptor type
• The same NT released in different locations may have a
different influence on the effectors (inhibitory/ excitatory)
• This leads to the conclusion that there are different subtypes
of receptors that can react with the same NT
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The effect of neurotransmitter on
the postsynaptic membrane
depends on the properties of
the receptor
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
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Neurotransmitter Receptor Mechanisms
• Direct: neurotransmitters that open ion channels
• Promote rapid responses
• Examples: ACh and amino acids
• Indirect: neurotransmitters that act through second
messengers
• Promote long-lasting effects
• Examples: biogenic amines, peptides, and dissolved
gases
PLAY
InterActive Physiology ®:
Nervous System II: Synaptic Transmission
Copyright © 2010 Pearson Education, Inc.
Channel-Linked Receptors
• Composed of integral membrane protein
• Mediate direct neurotransmitter action
• Action is immediate, brief, simple, and highly localized
• Ligand binds the receptor, and ions enter the cells
• Excitatory receptors depolarize membranes
• Inhibitory receptors hyperpolarize membranes
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Direct effect – receptors are part of the ion channel
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G Protein-Linked Receptors
• Responses are indirect, slow, complex, prolonged, and
often diffuse
• These receptors are transmembrane protein complexes
• Examples: muscarinic ACh receptors, neuropeptides,
and those that bind biogenic amines
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Indirect effect – through G-protein and 2nd messenger
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Neural Integration
• More synapses a neuron has the greater its information-processing
capability
• cells in cerebral cortex with 40,000 synapses
• cerebral cortex estimated to contain 100 trillion synapses
• Chemical synapses are decision-making components of the nervous
system
• ability to process, store and recall information is due to neural
integration
• Based on types of postsynaptic potentials produced by neurotransmitters
• Millions of neurons in the CNS are organized in neuronal pools –
functional groups that:
• Integrate incoming information
• Forward the processed information
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Neural pools
• Neural pool
• neurons that share specific function
• Groups of neurons that influence each other’s activities
• Simple pool
• Consist of input fibers (presynaptic neurons) and output fibers
(postsynaptic neurons).
• Postsynaptic fibers
• Discharge zone – neurons most closely associated
with the incoming fiber – most likely to generate
impulses
• Facilitated zone – neurons farther away from
incoming fiber
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Neural Pools and Circuits
• In discharge zone, a single cell can produce firing
• Output neurons in discharge zone form sufficient
synapses with a single input neuron to discharge or fire
when that input neuron fires.
• in facilitated zone, single cell can only make it easier
for the postsynaptic cell to fire
• Output neurons in facilitation zone do not form
enough synapses with that input fiber and will not
discharge in response to that input fiber, but will be
brought closer to threshold for firing (facilitation).
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Types of Circuits in Neuronal Pools
• Divergent – one incoming fiber stimulates increasing number of
fibers:
• Amplification - Signal spreads to an increasing number of
neurons as it moves through successive orders of a neuronal
pathway.
• Example - a signal from a single motor cortex neuron can
excite 10,000 muscle fibers.
• Divergence into multiple tracts - A signal can split and go to
two different destinations within the nervous system.
• Example - sensory information from the spinal cord splits
and goes to cerebellum and to cerebral cortex.
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Figure 11.24a, b
Types of Circuits in Neuronal Pools
• Convergent – opposite of
divergent circuits, resulting in
either strong stimulation or
inhibition
• in both sensory and motor
systems
• The pool receives inputs from
several presynaptic neurons
• The pool has a concentrating
(funneling) effect
• Explains different stimuli that
have the same effect.
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Figure 11.24c, d
Types of Circuits in Neuronal Pools
• Reverberating/oscillating – incoming signal travels along chain of
neurons containing collateral synapses with previous neurons in
the chain
• Uses positive feedback within a neuronal circuit to re-excite
the input of the same circuit.
• Initial stimulus may only last for one msec but output will last
for many msec to minutes.
• Circuit is eventually stopped by progressive synaptic fatigue
or by inhibitory circuits
• This gives a continuous signal involved in rhythmic activities
(sleep-awake cycle, breathing)
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Figure 11.24e
Types of Circuits in Neuronal Pools
• Parallel after-discharge – incoming neurons stimulate
several neurons in parallel arrays that stimulate a
common output cell
• Example – precise activity (math calculation)
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Figure 11.24f