2) Neurophysiology
2) Neurophysiology
1
The Nervous System
• The Nervous System is the master controlling
and communication system of the body,
specialized to quickly detect and respond to
stimuli.
• It is composed of:
• Central Nervous System (brain, spinal cord)
– Integration
• Peripheral Nervous System (peripheral nerves
and receptors).
– Afferent Division (Sensory information IN)
– Efferent Division (Motor responses OUT)
2
Central nervous system (CNS)
Brain and
Input Output
spinal cord
to CNS from
from CNS to
periphery periphery
Peripheral nervous
system (PNS)
Afferent Efferent
division division
Stimuli in
Sensory Visceral Somatic Autonomic digestive
stimuli stimuli nervous system nervous system tract
KEY
• Functions:
– Electrical
& Chemical
Communication
– Sensory Input
– Integration
– Motor Output
4
Central Peripheral
nervous system nervous system
(spinal cord)
Cell
Axon body Afferent neuron
terminals
Interneuron
Efferent neuron*
Effector organ
(muscle or gland)
Axon
(efferent fiber) Axon
Cell
body terminals
Ependymal
cell
Brain
interstitial Neurons
fluid
Astrocyte
Oligodendrocyte Capillary
Microglia
7
Fig. 5-3, p. 138
8
Table 5-1 p138
Neuron Structure
Neuron structure reflects its function in stimulus
response and communication
• dendrites: receive input from other cells or receptors
• cell body: contains the nucleus
• axon hillock: integrates electrical input from dendrites,
highly excitable region
• axon: transmits electrical input to the axon terminal
• axon terminals: end of the axon, contacts the next cell
and releases chemical neurotransmitters
9
1) Input zone receives incoming
signals from other neurons.
Dendrites
Cell body
2) Trigger zone
initiates action 3) Conducting zone conducts
potentials. action potentials in undiminishing
Nucleus fashion, often over long distances.
Axon hillock
Axon (may be from 1mm
to more than 1 m long)
Axon
terminals
Dendrites 4) Output zone releases
neurotransmitter that
Cell body influences other cells.
Axon
10
Fig. 4-8, p. 98
Synapses
11
Neuron Communication
Neurons communicate electrically through
electrical gradients and
chemically through neurotransmitters
• electrical communication: movement of ions in an
out of cell membranes
• can be small, local or travel long distances down the
branches of the cell
• chemical communication: release of
neurotransmitters (ligand) to nearby
neurotransmitter receptors (receptor) at synapses
12
Stimuli Activate Neurons
• Neurons are excitable, and are activated by stimuli to send
signals to other cells
• stimulus: a stimulus is any change in the environment that
triggers a change in the neuron
– mechanical (touch, vibration, movement)
– electrical (ion, voltage changes)
– chemical (taste, smell, ligands from other cells)
• Activation happens through activation of channels on
dendrites
– stimulus comes in and changes the shape of the channel, the
channel then transmits via electrical and/or chemical changes
inside the cell. 13
Types of Ion Channels found in Neurons
• Mechanically gated channels – open in response to physical forces
• Voltage-gated channels – open or close in response to changes in electrical
membrane potential.
• Ligand-gated channels – chemically gated, open when chemicals or
neurotransmitters bind.
• Leaky channels – always open, non-gated
14
Electrical Communication
15
Membrane Potential
• Membrane potential is defined as the amount of electrical
charge present on the inside of the cell (ICF) compared to the
outside of the cell membrane (ECF).
• POSITIVE membrane potential: the inside of the cell is more
positive than the outside of the cell
• more positive ions (ex: K+) inside the cell than outside the cell
• OR that there are more negative ions (ex: Cl-)outside the cell
• NEGATIVE membrane potential: the inside of the cell is less
positive than the outside of the cell
• means there are more negative ions inside the cell (ex: Cl-) than
outside the cell
• OR that there are more positive ions (ex: Na+) outside the cell.
16
Resting Membrane Potential
17
Concentration gradient of ions
18
Membrane Potential in Neurons
19
Membrane Potential Values
• Taking into account the A- , Na+ and K+, a
general neuron has a membrane potential of
-70mV when no electrical signaling is occurring,
this is resting membrane potential
+35 mV
• All changes in membrane potential due to
noitaziraloped
signaling are now compared to REST 0 mV
noitaziraloprep yh
-105 mV
• Then + ions move OUT of the cell, the
membrane potential will become less
positive (more negative), this is called
hyperpolarization.
20
Forces on Ion Movement
• The Na+ and K+ ions are affected by electrical gradients and
their individual concentration gradients
• FORCES on K+ (inside):
• concentration gradient: K+ wants to move OUT of the cell
• electrical gradient: the negative membrane potential wants to keep K+
IN the cell
• If these could balance out, equilibrium for K+ is reached, this is at
-90mV
• FORCES on Na+ (outside):
• concentration gradient: Na+ wants to move IN to the cell
• electrical gradient: the negative membrane potential pulls Na+ IN to
the cell
• IF these could balance out, equilibrium for Na+ is reached, this is at
21
+60mV
Plasma membrane
ECF ICF
Concentration
gradient for K+
Electrical
gradient for K+
22
EK+ = –90 mV Fig. 3-20, p. 83
Plasma membrane
ECF ICF
Concentration
gradient for Na+
Electrical
gradient for Na+
ECF
anions,
mostly
23
ENa+ = +60 mV Fig. 3-21, p. 84
+ +
Na and K Channels at rest
• The movement of ions will be determined by the type
of ion channels that are present.
• At rest:
• K+ channels:
– leaky K+ channels: when the neuron is at rest: passive,
open K+ channels allow K+ to leak out of the cell, nearing
it equilibrium.
– K+ permeability at rest is high, but not complete
• Na+ channels:
– when the neuron is at rest: there are very few open Na+
channels
– Na+ permeability at rest is low, very far from its 24
Electrical Signaling in Neurons
Na + channel
reset to closed
but capable
Na + channel of opening K + channel
opens and (activation closes
is activated gate closes; (activation
inactivation gate closes)
es a hp g nisir
(activation
gate opens; gate opens)
t u o +K
inactivation
gate already
open)
→
→
3
ll af
5
ni + a N
es a hp g ni
K + voltage-gated channel closed
(activation gate closed)
2
Threshold potential
1 6
Resting potential 8
7
Depolarizing
triggering event
Extracellular fluid
Closed channels Unbalanced charges
distributed across the
plasma membrane that
are responsible for
Portion of membrane potential
Intracellular fluid
an excitable
cell
27
Fig. 4-2a, p. 92
Membrane Potential changes
+20
+10 Depolarization (decrease in potential;
)Vm( laitnetop enarbmeM
0 membrane less negative)
–1
0 Repolarization (return to resting potential
–2
after depolarization)
0
–3
0
–4 Hyperpolarization (increase in
0
–5 potential; membrane more negative)
0
–6
0
–7 Resting potential
0
–8
0
–9
0
Time (msec)
28
Fig. 4-1, p. 90
Electrical Signaling Types
• There are two main ways that membrane potential
changes in neurons:
• Graded Potential: a small, local change in membrane
potential that can vary in size, and does not travel far
• caused by small changes in nearby connected cells or
receptors
• used for fine-tuned information, can build up to become a
larger trigger
• Action Potential: a large, fast, long distance spread of
membrane potential change that is the same magnitude
every time it occurs
• caused by large changes and/or multiple connecting cells or
receptors changing
• all or none signal to communicate on/off triggers between 29
Graded Potentials
• Graded Potentials:
• small, local membrane potential changes due to a
triggering event
• gated ion channels open for a short time in a small
section of the membrane
• ion specific to that channel moves passively with its
gradient
• local current flows change membrane potential in a
small area, but signal is dissipated with distance from
gated ion channels that first open
• Excitatory: positive ions move IN (example: Na+)
• Inhibitory: negative ions move IN (example Cl-), or
30
positive ions move OUT (example K+)
Graded Potentials
Triggering event opens ion channels, most commonly permitting net Na+ entry
31
Fig. 4-2b, p. 92
Graded Potentials Dissipate
Current flows between the active and adjacent inactive areas
32
Fig. 4-2c, p. 92
Action Potentials
• Action Potentials:
• a large, fast, long distance spread of membrane potential
change
• graded potentials build up until a threshold is reached in
the cell
• starts at one triggered site, but is propagated down the
entire cell without dissipating
• the same magnitude every time it occurs (All or none)
• the same exact pattern of membrane potential changes
every time it occurs
• one-way propogation down the axon toward the synaptic 33
Action Potential Pattern
• Once triggered, an action potential has the
exact same pattern every time it occurs:
1. REST: Membrane Starts at rest
2. THRESHOLD: Threshold reached?
3. RISING PHASE: Depolarization
4. FALLING PHASE: Repolarization
5. DIP: Hyperpolarization
6. Return to Rest
34
+70
+60
+50
+40
+30
37
Action Potential Events: THRESHOLD
THRESHOLD: Threshold reached?
• -50 to -55 mV
• Due to build up of triggering events
(graded potentials!) and a
combination of ions moving,
depending on the input to the cell
SIGNAL IS TURNED ON
38
Action Potential Events: RISING PHASE
Na+ RUSHES IN
39
Action Potential Events: FALLING PHASE & DIP
FALLING PHASE: Repolarization
• moves down toward -70
• DUE to K+ moving out
• K+ leaky channels open
• Na+ voltage gated channels inactive
• K+ voltage gated channels open
DIP: Hyperpolarization
• moves toward -90
• K+ voltage gated channels continue to stay
open past resting membrane potential
K+ MOVES OUT
40
Action Potential Events: Final Rest
Return to Rest:
• the Na/K pump re-estabilishes the original
gradients
• K+ leaky channels open
• Na+ voltage gated channels closed, ready again
• K+ voltage gated channels closed
41
Action Potential Refractory Periods
Action potential timing is key for electrical signaling, so the
overlap of actions potentials is limited by two refractory
periods
Absolute Refractory Period: NO other action potentials can
occur during this time because Na+ channels are either
maximally open or inactive
• during rising phase and repolarization
Relative Refractory Period: another action potential can only
occur if the triggering stimulus is very large because only
a few Na+ channels are available and K+ is exiting the
cell, opposing depolarization triggers that may come in.
• during dip phase (“after hyperpolarization”)
42
Graded Potentials are Input to the
Dendrites
43
1) Input zone receives incoming
signals from other neurons.
Dendrites
Cell body
2) Trigger zone
initiates action 3) Conducting zone conducts
potentials. action potentials in undiminishing
Nucleus fashion, often over long distances.
Axon hillock
Axon (may be from 1mm
to more than 1 m long)
Axon
terminals
Dendrites 4) Output zone releases
neurotransmitter that
Cell body influences other cells.
Axon
44
Fig. 4-8, p. 98
Action Potential Propogation
Action potentials spread in an ALL or NONE fashion down
the axon once they are triggered at the axon hillock
• Once a group of Na+ voltage gated channels reaches
threshold, Na+ rushes in, bringing successive patches of
membrane to threshold, and creating of opening more
Na+ voltage gated channels
Action potentials ONLY move in one direction, down the axon
toward the axon terminal. Due to temporary inactivation of
Na+ voltage gated channels
45
Adjacent inactive area into
Active area at which depolarization is
peak of action spreading; will soon reach Remainder of axon
potential threshold still at resting potential
46
Fig. 4-9a, p.
Adjacent area
that was
brought to New adjacent
Previous active threshold by inactive area
area returned local current into which
to resting flow; now depolarization is
potential; no active at peak spreading; will soon
longer active; in of action reach threshold Remainder of axon
refractory period potential still at resting potential
47
Fig. 4-9b, p.
New adjacent inactive area
Previous active New active area into which depolarization
area returned to at peak of action is spreading; will soon reach
resting potential potential threshold
49
Myelination & Saltatory Conduction
Myelination: myelin is a thick lipid-rich layer that is formed by
oligodendrocytes (CNS) or Schwann cells (PNS)
• up to 300 layers thick, insulates the axons
• no ion channels or ion flow under myelin
• discontinuous chunks of myelin, with spaces between (Nodes of
Ranvier)
Saltatory Conduction: myelination allows this fast, efficient
conduction to take place in axons
• ions and electrical charge only move at Nodes of Ranvier
• voltage gated Na+ and K+ channels concentrated at Nodes of
Ranvier
• increases efficiency, fewer Na/K pumps needed
• electrical potential jumps from node to node, increasing the speed
50
of conduction
Nodes of Ranvier Myelin sheath
Myelin
sheath
Axon
Axon of neuron
Plasma
membrane
Cytoplasm
Nucleus
Schwann cell
Node of Ranvier
Nodes of Oligodendrocyte
Ranvier
53
Fig. 4-12c, p. 103
Adjacent inactive node
into which depolarization
Active node at peak is spreading; will soon Remainder of nodes
of action potential reach threshold still at resting potential
Direction of propagation
of action potential
54
Fig. 4-13, p. 104
Adjacent node that was New adjacent inactive
Previous active node brought to threshold by node into which
returned to resting local current flow now depolarization is
potential; no longer active at peak of action spreading; will soon
active potential reach threshold
55
Fig. 4-13, p. 104
Axon Diameter
Axon Diameter: the width of the axon determines the
resistance to electrical current flow
Large diameter axons: low resistance, fast conduction
• up to 120 meters/second (268 mph)
• example: neuron to skeletal muscle
Small diameter axons: high resistance, slower conduction
• as low as 0.7 meters/second (2 mph)
• example: neuron to digestive organs
• NOTE: Space is limited, so if an axon needs to have fast
transmission, it will be both large diameter and
myelinated
56
Neuron Communication
• Neurons communicate electrically through
electrical gradients and chemically through
neurotransmitters
• electrical communication: movement of
ions in an out of cell membranes
• can be small, local or travel long distances
down the branches of the cell
• chemical communication: release of
neurotransmitters (ligand) to nearby
neurotransmitter receptors (receptor) at
synapses
Synapses 1. Synapses with another neuron
between two
neurons or 2. Neuromuscular synapses
Neuromuscular synapses
between a neuron Neuron
and a muscle,
gland, or cell
Skeletal
muscle
3. Neuroglandular synapses
Neuroglandular
Neuron synapses
Gland cells
Neuron Communication
• At the connection between two neurons there
is a space (synaptic cleft) that does not allow
electrical current to flow, so a chemical
signal is required as an intermediate.
• Communication between two neurons is
always:
– ELECTRICAL: action potential in 1st (pre-synaptic)
cell
– CHEMICAL: neurotransmitter released to cross
synapse
– ELECTRICAL: graded or action potential in 2nd
(post-synaptic) cell
Synapses Presynaptic neuron
Structures of a
Synapse:
•
Presynaptic Synapse
•
Synaptic cleft
•
Postsynaptic
neuron
Axon Terminal
Synaptic vesicles
Presynaptic membrane
Synaptic cleft
Postsynaptic membrane
Presynaptic Neuron
Presynaptic neuron
Postsynaptic neurons
Axon Terminal
Synaptic vesicles
Presynaptic membrane
Synaptic cleft
Postsynaptic membrane
Postsynaptic Neuron
Presynaptic neuron
membrane
Synapse
A synapse contains specialized structures to transmit
electrical and chemical signals
Events at the Synapse
Pre-synaptic events at the axon
terminal:
1. ACTION POTENTIAL
Ca 2+ ENTRY
2.
3. NT RELEASE
Post-synaptic events at the dendrite:
4. NT RECEPTOR ACTIVATION
5. IONS ENTER
6. GRADED POTENTIAL
1. Action Potential Reaches Axon Terminal
After traveling through the pre-synaptic axon, the axon
potential reaches the presynaptic axon terminal
This depends solely on electrical conduction through the
axon. 1
Axon of
presynaptic
neuron
2. Calcium enters the Axon Terminal
Voltage gated Ca2+ channels are present in the axon
terminal. When the action potential enters, voltage
gated Ca2+ channels open and calcium enters the
axon terminal
Voltage-gated
Ca2+ channel
3. Neurotransmitter Release
Vesicles filled with neurotransmitter, called synaptic
vesicles are in the axon terminal.
Ca2+ entry into the pre-synaptic terminal is the signal
that causes exocytosis of these vesicles and release
of neurotransmitter at the axon terminal
Synaptic
vesicle
Synaptic
vesicle
4. Neurotransmitter Receptor Activation
Neurotransmitter diffuses across the synaptic cleft and
binds to neurotransmitter receptors on the post-synaptic
cell membrane
Postsynaptic
dendrite
Summary Events at the Synapse
1. ACTION POTENTIAL PRE-SYNAPTIC: axon potential
reaches the presynaptic axon terminal
2. Ca2+ ENTRY PRE-SYNAPTIC: Voltage gated Ca2+
channels in the axon terminal open in response to the
action potential, Ca2+ enters the axon terminal
3. NT RELEASE: Ca2+ causes release of neurotransmitter
via exocytosis at the axon terminal
4. NT RECEPTOR ACTIVATION: neurotranmitter binds to
neurotransmitter receptors on the post-synaptic
membrane
5. IONS ENTER POST-SYNAPTIC: neurotransmitter
receptor activation opens ion channels in the post-
synaptic membrane
6. GRADED POTENTIAL in the post-synaptic cell dendrite
(can lead to ACTION POTENTIALS)
Summary Events at the Synapse
1
Axon of
presynaptic
neuron
Voltage-gated 3
Ca2+ channel Synaptic knob
Ca 2 (presynaptic
+ axon terminal)
2
Synaptic
Neuro- vesicle
transmitter
molecule 3 Synaptic
cleft
Subsynaptic 4
membrane
5
4
Chemically gated
receptor-channel
for Na +, K +, or Cl– Receptor for
neurotransmitter 5 Postsynaptic neuron
Activation of synapse
Threshold
–5
potential
0 EPSP
–7
0
5 15 25 35 45
Time (msec)
(a) Excitatory synapse
Fig. 4-16a, p.
)Vm( laitnetop enarbmeM
+30
noruen citpanystsop ni
0
Activation of synapse
Threshold
–5
potential
0
–7
0 IPSP
5 15 25 35 45
Time (msec)
(b) Inhibitory synapse Fig. 4-16b, p.
Reaching Threshold (post-synaptic)
There are many inputs to Dendrites Synaptic inputs
one neuron. EPSPs and (presynaptic axon terminals)