General Properties of Chemical Synaptic Transmission
1- One – Way Conduction
2- Synaptic Delay
3- Synaptic Fatigue
4- Post-Tetanic Facilitation
5- Long - Term Potentiation
6- Effect of Hypoxia on Synaptic Transmission
7- Effects of pH on Synaptic Transmission
8- Effect of Drugs on Synaptic Transmission
1- One – Way Conduction:
* At synapses, conduction of impulses occurs in one direction
only; from the presynaptic to the postsynaptic neurons & not in the
opposite direction.
* This is known as “Bell- Magendie law”.
Mechanism:
- Action potential generated at the initial segment of
the axon will travel in 2 directions:
a) along the axon toward its terminal endings ; orthodromic
(forward conduction):
The forward impulse -----> transmitter release from the synaptic
knobs ----> action on the postsynaptic neuron (excitation or
inhibition).
b) Spread back over the soma & dendrites, antidromic (backward
conduction):
The backward impulse produces no effect because there are no
transmitter vesicles in the presynaptic neuron.
Also, impulses travelling backword on the postsynaptic
neurons can’t excite the presynaptic neuron.
2- Synaptic Delay:
Definition :
It is time passed between arrival of an action potential to the
synaptic knob and the occurrence of response in the postsynaptic
neuron .
- This represents the time required for:
a) Release and diffusion of the neurotransmitter
b) Binding of the transmitter to the postsynaptic receptors.
c) Generation of PSPs & its summation to generate action
potential.
- The minimum time for synaptic delay is about 0.5 millisecond.
- Significance:
can be used to determine the number of synapses present in a
polysynaptic reflex .
3- Synaptic Fatigue:
Definition :
- It is progressive decline in rate of discharge of the postsynaptic
neuron, following intense prolonged stimulation of the presynaptic
neuron.
- In sever conditions, synaptic transmission completely stops. This
is called "synaptic block".
Mechanism:
Depletion of the stores of the neurotransmitter in the synaptic
knobs, because there is no enough time resynthesis and reuptake
mechanisms that refill the stores under intensive stimulation.
Synaptic fatigue disappears when the transmitter has been
replenished.
- Hypoxia accelerate synaptic fatigue while strychnine delays it.
Significance:
* Under normal conditions, rates of resynthesis and reuptake of
the neurotransmitter are sufficient for synaptic transmission for
long periods of time without the development of fatigue.
*
Synaptic
fatigue
when
occurs
protects
overexcitability (a protective mechanism).
CNS
from
4- Post-Tetanic Facilitation:
Rapid repeated stimulation of the presynaptic terminal (at a rate
stoppage
not producing fatigue) for a period of time --------------->
then
restimulation shows ↑ postsynaptic discharge above normal for a
period of seconds or even minutes.
- This is called post-tetanic
facilitation or potentiation.
Mechanism:
- It is caused mainly by excess rise of the concentration of Ca2+
ions in the synaptic knob which causes more and more vesicles to
release their transmitter, producing a greater response of the
postsynaptic neuron.
Significance:
- It is still unclear, but it may have a role in the short-term
memory processes in the central nervous system .
5- Long - Term Potentiation:
Brief rapid repeated stimulation of presynaptic terminal ----->
prolonged ↑in rate of postsynaptic discharge.
- It resembles post-tetanic potentiation, but is much more
prolonged and can last for several days .
Mechanism:
It is initiated mainly by an increase of the intracellular Ca2+
concentration in the postsynaptic neuron through opening of
certain Ca2+ channels in the postsynaptic membrane . After
binding of glutamate to its specific NMDA receptros.
Significance:
It occurs in many parts of the nervous system , but it has a special
significance in the hippocampus; which plays an important role in
learning and memory.
6- Effect of Hypoxia on Synaptic Transmission:
- Hypoxia ↓neuronal excitability & synaptic transmission.
- This is due to the need of the neurons for adequate oxygen
supply.
- interruption of cerebral circulation for about 7 seconds causes
loss of consciousness (coma) & for about 2-3 minutes causes
irreversible damage of the brain.
7- Effects of pH on Synaptic Transmission:
- In brain synapses, alkalosis ↑ excitability and synaptic
transmission while acidosis ↓it.
- So, ↑pH to 7.8 to 8.0, produces severe convulsions whereas,
↓pH around 7.0 produces coma. This latter condition is always
seen in severe uremic or diabetic acidosis .
8- Effect of Drugs on Synaptic Transmission:
Drugs ↑ing neuronal excitability
& synaptic transmission
Drugs ↓ ing neuronal excitability
& synaptic transmission
1- Caffeine (found in coffee) and 1- Volatile anesthetics:
theophylline (found in tea ): ↑ threshold needed for excitation
↓threshold needed for excitation of the postsynaptic neuron.
of the postsynaptic neuron.
2- Strychnine:
inhibits the action of glycine 2- Tranquilizers:
(inhibitory neurotransmitter) on ↑Cl -influx ----> inhibition of
the neurons.
postsynaptic neurons at specific
regions in the nervous system.
General Properties of Chemical Synaptic Transmission
1- One – Way Conduction
2- Synaptic Delay
3- Synaptic Fatigue
4- Post-Tetanic Facilitation
5- Long - Term Potentiation
6- Effect of Hypoxia on Synaptic Transmission
7- Effects of pH on Synaptic Transmission
8- Effect of Drugs on Synaptic Transmission
NEUROTRANSMITTERS
IN
THE CENTRAL NERVOUS SYSTEM
Neurotransmitters of the central nervous system can be broadly
classified into two groups:
(i) Small- molecule neurotransmitters.
)ii) Neuropeptides.
Small - Molecule Neurotransmitters
- Rapidly acting, causing most of the fast responses of the
nervous system, such as transmission of sensory impulses to the
brain and motor signals to the muscles.
- Synthesized in the presynaptic terminals.
- Stored in vesicles in the presynaptic terminals.
- Released during the process of synaptic transmission to act on
the postsynaptic membrane receptors .
Small - Molecule Neurotransmitters
Class I
Acetylcholine
Class II (Biogenic Amines)
Dopamine
Norepinephrine
Serotonin
Histamine
Class III (Amino Acids)
Glutamate
Aspartate
γ- Aminobutyric acid (GABA)
Glycine
Class IV
Nitric oxide (NO)
Carbon monoxide (CO)
Acetylcholine :
- Synapses that release acetylcholine are known as cholinergic
synapses .
- These are widely distributed in the central nervous system .
- There are two types of receptors that can bind acetylcholine :
1- Nicotinic Acetylcholine Receptors.
2- Muscarinic Acetylcholine Receptors.
1- Nicotinic Acetylcholine Receptors.
- These receptors are ligand- gated ionic channels.
- Once activated by binding with acetylcholine, the receptor
opens its gate to permit influx of Na+ ions, causing
depolarization (EPSP) in the postsynaptic membrane.
2- Muscarinic Acetylcholine Receptors
- Five types of muscarinic receptors have been identified (M1 to
M5 receptors).
- All are G – proteinscoupled receptors.
- Activation of M1
receptors closes K+ channels causing
depolarization and excitation of the postsynaptic neuron
- Activation of M2
receptors causes opening of K+ channels
causing hyperpolarization and inhibition of the neuron.
1
Gs protein
closes
Depolarization
Small - Molecule Neurotransmitters
Class I
Acetylcholine
Class II (Biogenic Amines)
Dopamine
Norepinephrine
Serotonin
Histamine
Class III (Amino Acids)
Glutamate
Aspartate
γ- Aminobutyric acid (GABA)
Glycine
Class IV
Nitric oxide (NO)
Carbon monoxide (CO)
Dopamine
- Secreted as a transmitter by dopaminergic neurons, located
largely in the substania nirga of the midbrain, which project their
axons mainly to the basal ganglia.
- Five types of dopamine receptors have been identified (D1 to D5
receptors), and all are acting through the G-proteins second
messenger system.
- Dopamine can produce either an excitatory or an inhibitory effect
depending upon the type of its postsynaptic receptor .
- The action of released dopamine is terminated mainly by its rapid
reuptake into the presynaptic terminal, where it is stored once more
in synaptic vesicles .
Norepinephrine
- Norepinephrine is secreted by noradrenergic neurons whose cell
bodies are located mainly in a region called the “locus ceruleus”
in the pons, from which the noradregnergic neurons send nerve
fibers both downward to the spinal cord , and upward to
widespread areas of the brain.
- The receptors for norepinephrine include both alpha () and beta
() adrenergic receptors. Both groups act through G-proteins, and
there are multiple form of receptors in each group .
- In many of these areas ,norepinephrine appears to activate
excitatory receptors ,but in some other areas it activates inhibitory
receptors .
- After dissociation from its receptor, most of the norepinephrine is
taken back into the presynaptic terminal where it is stored in synaptic
vesicles in preparation for release again into the synaptic cleft
- One important function of epinephrine is to control the activity of
certain brain centers that play an important role in regulating the
psychological mood.
Serotonin
- Serotonin secreting neurons in the nervous system are located in
the“ raphe nuclei ”in the brain stem , which project their axons
to many areas in the brain and spinal cord .
- After dissociation from its receptor, most serotonin is transported
back into the presynaptic terminal by an active reuptake
mechanism
- Serotonin is involved in the activation of the pain control system
in the spinal cord, and its action in the higher regions of the nervous
system (the brain and brain stem) is believed to control the mood of
the person and plays a role in sleep .
Small - Molecule Neurotransmitters
Class I
Acetylcholine
Class II (Biogenic Amines)
Dopamine
Norepinephrine
Serotonin
Histamine
Class III (Amino Acids)
Glutamate
Aspartate
γ- Aminobutyric acid (GABA)
Glycine
Class IV
Nitric oxide (NO)
Carbon monoxide (CO)
Glutamate
- It is the most abundant excitatory transmitter in the nervous
system
- It is found in most areas of the brain and spinal cord .
- It activates ligand-gated cation channels, allowing increased
Na+ and Ca++ influx, thus causing excitation of the postsynaptic
neuron.
Gamma- Amino Butyric Acid (GABA):
- It is the major inhibitory transmitter in the brain
- It is a potent postsynaptic & presynaptic inhibitor
- GABA activates Cl- channels and K+ channels, allowing
increased Cl- influx and increased K+ efflux. Both effects cause
hyperpolarization and inhibition of the postsynaptic neuron .
Glycine
- It is a neurotransmitter responsible for
direct inhibition of
synapses (postsynaptic inhibition) .
- It is secreted by interneurons located in certain regions of the brain
stem and spinal cord .
- Glycine exerts its inhibitory effect by increasing Cl- conductance
(Cl- flow currents) through a ligand - gated Cl- channel in the
postsynaptic membrane.
Neuropeptides
- Several families of peptides with relatively high molecular
weight whose actions are usually slow and prolonged.
- Synthesized in the soma of neurons rather than in the synaptic
terminal
- Stored within secretory vesicles that are then transported to the
nerve terminals by the mechanism of “axonal streaming” of the
axon cytoplasm.
- Examples: Substance P, Neuropeptide Y.
Change in the number of postsynaptic receptors
Prolonged effect on calcium channels
4
2
3
1