NS5 Lecture 5 of 63 in the Neuroscience Module "Synaptic Transmission" [Physiology]

1. NS5 – SYNAPTIC TRANSMISSION
NS5 – SYNAPTIC TRANSMISSION
I. OVERVIEW
A. SYNAPTIC TRANSMISSION: mechanism of neuron-neuron or neuron-muscle/gland communication.
B. DESCRIPTION: neurons sense changes in the environment, communicate with each other, and other
tissues and organs using electrical and chemical signals
1. ELECTRICAL SIGNALS: change in membrane potential
a. GRADED POTENTIAL: small currents that are generated in response to stimuli and travel short
distances. They may either dissipate or summate to generate an action potential.
i. GENERATOR POTENTIALS are caused by energy (heat, light etc) .
ii. RECEPTOR POTENTIALS are caused by energy (heat, light etc).
iii. POST-SYNAPTIC POTENTIALS are caused by chemicals.
b. ACTION POTENTIAL: a brief pulse of electrical current that travels along an axon and triggers
neurotransmitter release at the axon terminal.
2. CHEMICAL SIGNALS: neurotransmitters and receptors
II. REVIEW
A. PRINCIPLES OF ELECTRICITY
1. VOLTAGE (V): measure of potential energy; millivolts
2. POTENTIAL: difference in voltage
3. CURRENT (I): flow of electrical charge; milliamps
4. RESISTANCE (R): block or hindrance to electrical flow; ohms
5. OHM'S LAW: V = I/R
B. MEMBRANE POTENTIAL
1. Definition: difference in voltage across membranes that is created and maintained by
a. a concentration gradient of ions
Table 1: Concentration of key ions involved in resting membrane potential
concentration flow
concentration
ion inside cell
outside cell (mM)
(mM)
diffuses into cell via passive channel
Na+ 150 15 pumped out of cell via Na+/K+ pump
diffuse out of cell
K+ 5 150 pumped into cell via Na+/K+ pump
requires gated channel for transport
Cl- 120 10
too large to diffuse out of cell
A- (proteins) 0.2 100
b. the selective permeability of the membrane to ions via ion channels
2. Useful link with animation
http://www.lifesci.ucsb.edu/~mcdougal/neurobehavior/modules_homework/animation2.html
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2. NS5 – SYNAPTIC TRANSMISSION
C. MEMBRANE ION CHANNELS
1. Function: regulate movement of ions into and out of cell.
2. Types
a. PASSIVE or LEAKAGE CHANNELS
b. ACTIVE or GATED
i. Ligand-gated (chemical)
ii. Voltage-gated
iii. Mechanically-gated
D. CHANGE IN RESTING MEMBRANE POTENTIAL:
1. Causes
a. change in membrane permeability
b. change in ion concentrations
2. Types
a. DEPOLARIZATION – membrane potential becomes less negative compared to resting potential
b. HYPERPOLARIZATION – membrane potential becomes more negative compared to resting
potential
III. SYNAPSES
A. Definition: The junction between two neurons or a neuron and an effector cell. The transmitting cell is
identified as the presynaptic neuron and the receiving cell is identified as the postsynaptic neuron/cell.
B. Types
1. ELECTRICAL SYNAPSE:
a. Definition: an intercellular junction between two cells formed by integral membrane proteins that span
the membranes of both cells to form a hydrophilic channel, 2nm in diameter; also called gap junction.
b. Characteristics:
i. Membranes of both cells are touching each other.
ii. Junctions are usually between soma, axons and dendrites
c. Function:
i. permits unimpeded flow of ions and small solutes (glucose, nucleotides) between cells
ii. permits synchronization
d. Structural features: Junctions are formed by 2-hexamers of proteins called connexins
e. Distribution: skin, smooth muscle, cardiac muscle, retina, hippocampal neurons, cerebellar neurons,
GABA interneurons of neocortex, thalamus
f. disease: deafness, polyneuropathy, cataracts, skin disorders, cardiovascular disorders
2. CHEMICAL SYNAPSE:
a. Definition: the junction between two nerve cells from which a chemical signal is transmitted from the
presynaptic neuron and is received by a receptor/ligand or chemically-gated channel on the postsynaptic
membrane.
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3. NS5 – SYNAPTIC TRANSMISSION
III. SYNAPSES
2. CHEMICAL SYNAPSE (cont.):
b. Structural features:
i. Membranes of both cells are separated by a space called the synaptic cleft.
ii. The axon terminal (presynaptic terminal) contains synaptic vesicles filled with neurotransmitters.
iii. Vesicles fuse with the presynaptic membrane to release neurotransmitters into synaptic cleft.
iv. The dendritic terminal (postsynaptic terminal) contains ligand-gated channels that bind the
neurotransmitter.
v. Junctions can be between axon/dendrites, axon/soma, axon/axon, dendrite/dendrite,
dendrite/soma.
c. Function: communication of electrical information in the form of a chemical signal to from one neuron
to another neuron. The chemical signal is converted into an electrical signal in the postsynaptic neuron.
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4. NS5 – SYNAPTIC TRANSMISSION
IV. NEURONAL SIGNALLING
Table 2: Comparison of Graded Potentials and Action Potentials
Characteristics Graded Potentials Action Potentials
Arise in dendrites and soma Arise at trigger zones
Origin
Occurs in most membranes (not ex- Propagates along axon
citable)
Only possible at excitable membranes
Chemical (ligand) Voltage
Mechanical
Types of channels
Light
Heat
Localized (communication over a few Long distance communication
Conduction
mm)
Propagated
Not propagated
Depends on strength of stimulus All or none
Amplitude
< 1 mV to > 50mV 100 mV
Duration
msec – minutes 0.5 - 2 msec
Hyperpolarizing (inhibitory to genera- Depolarizing phase  repolarizing
tion of action potential) o phase  resting potential
Polarity
Depolarizing (excitatory to generation
of action potential)
Refractory Period
No Yes
Temporal and spatial summation No summation
Summation
Generator potentials
Receptor potentials
Types
Post-synaptic potentials
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5. NS5 – SYNAPTIC TRANSMISSION
IV. NEURONAL SIGNALLING
A. GENERATOR AND RECEPTOR POTENTIALS
1. Types
a. GENERATOR POTENTIALS are caused by energy (heat, light etc) and can elicit an action potential
in the sensor neuron. For example, stretch or pressure sensors.
b. RECEPTOR POTENTIALS are caused by energy (heat, light etc); they do not elicit an action
potential in the sensor neuron. For example, rod and cone cells.
2. Characteristics
a. Magnitude of response, that is, change in membrane potential depends on strength of stimulus.
b. A sum of multiple (temporal or spatial) graded potentials at the axon hillock is required to generate an
action potential.
3. Useful link: http://www.fortunecity.com/greenfield/buzzard/387/gradedpot.htm
B. ACTION POTENTIALS & SYNAPTIC TRANSMISSION
1. ACTION POTENTIALS
a. Phases: An action potential is divided into several phases. During each phase, different voltage
gated channels are activated.
Table 3: Phases of an Action Potential
Charge on inner State of voltage-gat- State of voltage-gated
Range of membrane ed sodium channel potassium channel
Phase membrane
potential, mV
closed
- 70 negative closed
Resting potential
opened after threshold
potential reached
Na+ flow into cell
negative changing
- 70 to +30 closed
Depolarization
to positive
cannot respond to sec-
ond stimulus (absolute
refractory period)
inactivated
may respond to second open
positive changing to
stimulus if greater than
+ 30 to -70
Repolarization
negative
threshold stimulus K+ ions flow out of cell
(relative refractory peri-
od)
closed closing
(relative refractory peri-
more negative than od) Na+/ K+ pump returns
-70 to -80
Hyperpolarization
resting potential
membrane potential to
resting
negative
-70 closed closed
Resting potential
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6. NS5 – SYNAPTIC TRANSMISSION
IV. NEURONAL SIGNALLING
B. ACTION POTENTIALS & SYNAPTIC TRANSMISSION
1. ACTION POTENTIALS
b. Propagation
i. Characteristics: self-propagated; away from initiation site (unidirectional)
ii. Mechanism:
• Local changes in membrane potential result in opening of voltage-gated channels.
• Ions flow into cell and diffuse in either direction. Change in membrane potential results in
opening of voltage-gated channels in membrane closer to axon terminal; inactivated voltage-
gated channels closer to axon hillock will not respond to change in membrane potential,
iii. Types
• CONTINUOUS: occurs in non-myelinated neurons; slow = 0.2-2 m/sec (velocity)
• SALTATORY: occurs in myelinated neurons; fast 12-20 m/sec (velocity)
iv. STIMULUS FREQUENCY but NOT stimulus strength INCREASES ACTION POTENTIAL
FREQUENCY.
c. Summation
i. Integration of depolarizing graded potentials allow for the generation of action potentials whereas
integration of a depolarizing and a hyperpolarizing potential results in no action potential.
ii. Types
• Temporal summation occurs when potentials overlap and generate a potential that is overall
larger than the individual potentials and allows for depolarization over the threshold which
results in an action potential.
• Spatial summation is the sum of potentials from different areas of input, usually on the
dendrites. Summation of excitatory postynaptic potentials (EPSPs) allows for depolarization
over the threshold and will generate an action potential. Summation of inhibitory postsynaptic
potentials (IPSPs) will block the generation of action potentials.
2. SYNAPTIC TRANSMISSION
a. Characteristics
i. Transmission depends on presynaptic release of neurotransmitter and postsynaptic reception of
neurotransmitters by receptors.
ii. Generates postsynaptic potentials in postsynaptic cell.
b. Mechanism:
i. Depolarization of membrane near axon terminal causes
• activation of voltage-gated sodium channels → influx of Na+ ions
• activation of voltage-gated calcium channels → influx of Ca++ ions
ii. Influx of Ca++ ions results in vesicle fusion to presynaptic membrane and exocytosis of
neurotransmitter. Calcium and sodium ion channels close and ions are pumped out.
iii. Neurotransmitter diffuses across synaptic cleft. Rate of diffusion causes synaptic delay.
iv. Neurotransmitter binds to receptor on post-synaptic membranes and generates postsynaptic
potentials.
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7. NS5 – SYNAPTIC TRANSMISSION
IV. NEURONAL SIGNALLING
B. ACTION POTENTIALS & SYNAPTIC TRANSMISSION
2. SYNAPTIC TRANSMISSION
b. Mechanism (cont.)
v. Unbound neurotransmitter either degraded or taken up by presynaptic membrane or astrocytes.
Bound neurotransmitters are degraded in the postsynaptic cell.
c. Synaptic Potentiation: repeated use of a synapse enhances neurotransmitter release.
d. Presynaptic Inhibition: regulation of neurotransmitter release by another synapse.
e. Neuromodulation of synaptic transmission
3. Links
http://www.lifesci.ucsb.edu/~mcdougal/neurobehavior/modules_homework/animation3.html
http://www.brainviews.com/abFiles/AniSalt.htm
http://outreach.mcb.harvard.edu/animations/synaptic.swf
http://www.williams.edu/imput/ (in depth)
C. POSTSYNAPTIC POTENTIALS
1. Definition: POST-SYNAPTIC POTENTIALS are graded potentials generated by neurotransmitters bind-
ing to receptors on postsynaptic membranes.
2. Mechanism:
a. Neurotransmitter binds to receptor.
b. Depending on neurotransmitter the outcome is either depolarization (excitatory) or hyperpolarization
(inhibitory).
c. Membrane permeability is regulated by a variety of channels: chemically (ligand or modulator)-gated
channels, voltage-gated channels.
2. Types
a. excitatory – will generate an action potential
b. inhibitory – reduces the ability to fire an action potential
Table 4: Comparison of EPSPs vs. IPSPs
membrane potential sodium channels potassium channels chloride channels
more positive than depolarization: open, depolarization closed closed
resting potential Na+ ion influx
repolarization
EPSP
< -70 mV (e.g. -70 to repolarization (return to open, K+ ion efflux
+30 mV) resting potential):
closed
more negative than closed hyperpolarization: hyperpolarization:
resting potential open, K+ ion efflux open, Cl- ion influx
depolarization (return
IPSP
> -70 mV (e.g. -70 to to resting potential): depolarization: depolarization:
-120 mV) open closed closed
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8. NS5 – SYNAPTIC TRANSMISSION
IV. NEURONAL SIGNALLING
D. NEUROTRANSMITTERS AND THEIR RECEPTORS
1. Definition: chemical signal synthesized by a presynaptic neuron and released at the axon terminal.
2. Neurotransmitter type (based on chemical structure; function: E = excitatory, I = inhibitory)
a. Acetylcholine (E)
b. Biogenic amines: dopamine (E/I), serotonin (I), norepinephrine (E/I), histamine
c. Amino acids: glutamate (E), aspartate (E), GABA (I), glycine (I)
d. Peptides: endorphins(I), enkephalins(I), dynorphins(I), tachykinin(E), somatostatin(I)
e. Lipids: anandamide (I, E)
f. Gases: NO (E), CO (I)
3. Neurotransmitter receptors
a. Definition: postsynaptic membrane proteins that bind presynaptically released chemical signal.
b. Types based on function
i. Direct action, ionotropic = channel-linked receptors
ii. Indirect action, metabotropic = G-protein coupled receptors
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