1. Synaptic transmission
Tada Obert
Department of Livestock & Wildlife Management
Midlands State University

2. Contents Introduction Excitatory synapses Inhibitory synapses
Neurotransmitters
Turning Synapses Off
Drugs and Synapses

3. Introduction
coordination of cellular activities in animals usually involve:
an endocrine system: where the response is to hormones
a nervous system: response to electrical impulses passing from the CNS to muscles and glands.
coordination by the NS is also chemical.
most neurons achieve their effect by releasing chemicals, the neurotransmitters, on a receiving cell on:
another neuron (a "postsynaptic" neuron)
a muscle cell
a gland cell

4. Introduction cont’d
Real distinction between nervous & endocrine coordination is that nervous coordination is faster and more localized
Neurotransmitters are chemicals that act in a paracrine fashion
The junction between the axon terminals of a neuron and the receiving cell is called a synapse.
Synapses at muscle fibers are also called neuro-muscular junctions or myo-neural junctions

5. The Synapse
Action potentials travel down the axon of the neuron to its end(s), the axon terminal(s).
Each axon terminal is swollen forming a synaptic knob.
The synaptic knob is filled with membrane-bounded vesicles containing a neurotransmitter.
Arrival of an action potential at the synaptic knob opens Ca2+ channels in the plasma membrane.
The influx of Ca2+ triggers the exocytosis of some of the vesicles.
Their neurotransmitter is released into the synaptic cleft.
The neurotransmitter molecules bind to receptors on the postsynaptic membrane.
These receptors are ligand-gated ion channels.

6. The neuro-muscular junction
nerve impulses traveling down the motor neurons of the sensory-somatic branch of the nervous system cause the skeletal muscle fibers at which they terminate to contract.
junction between terminal of motor neuron & muscle fiber is called the neuro-muscular junction.
the terminals of motor axons contain thousands of vesicles filled with acetylcholine (ACh).
when an action potential reaches the axon terminal, hundreds of these vesicles discharge their ACh onto a specialized area of postsynaptic membrane on the fiber.
this area contains a cluster of transmembrane channels that are opened by ACh and let sodium ions (Na+) diffuse in.

7. The neuro-muscular junction
the interior of a resting muscle fiber has a resting potential of about −95 mV.
influx of sodium ions reduces the charge, creating an end plate potential.
if the end plate potential reaches the threshold voltage (approx −50 mV), sodium ions flow in with a rush and an action potential is created in the fiber.
the action potential sweeps down the length of the fiber just as it does in an axon.

8. The neuro-muscular junction
no visible change occurs in the muscle fiber during (and immediately following) the action potential.
this period, called the latent period, lasts from 3 –10 msec.
before the latent period is over;
the enzyme acetylcholinesterase
breaks down the ACh in the neuromuscular junction (at a speed of 25,000 molecules per second)
the sodium channels close, and
the field is cleared for the arrival of another nerve impulse.
the resting potential of the fiber is restored by an outflow of potassium ions
the brief (1–2 msec) period needed to restore the resting potential is called the refractory period.

9. The neuro-muscular junction

10. Excitatory synapses
The neurotransmitter at excitatory synapses depolarizes the postsynaptic membrane (of a neuron the diagram above).
Example: Acetylcholine (ACh)
Binding of acetylcholine to its receptors on the postsynaptic cell opens up ligand-gated sodium channels.
These allow an influx of Na+ ions, reducing the membrane potential.
This reduced membrane potential is called an excitatory postsynaptic potential or EPSP.
If depolarization of the postsynaptic membrane reaches threshold, an action potential is generated in the postsynaptic cell.

11. Inhibitory synapses
The neurotransmitter at inhibitory synapses hyperpolarizes the postsynaptic membrane.
Example: gamma aminobutyric acid (GABA) at certain synapses in the brain.
Binding of GABA to:
GABAA receptors on the postsynaptic neuron opens up ligand-gated chloride (Cl−) channels (a fast response taking only about 1 millisecond).
GABAB receptors activates an internal G protein and a "second messenger" that leads to the opening of nearby potassium (K+) channels (a slower response, taking as long as 1 second).

12. Inhibitory Synapse Cont’d
In both cases, facilitated diffusion of ions (chloride IN; potassium OUT) increases the membrane potential (to as much as −80 mV).
This increased membrane potential is called an inhibitory postsynaptic potential (IPSP).
it counteracts any excitatory signals that may arrive at that neuron.

13. Neurotransmitters Acetylcholine (ACh) Amino acids Catecholamines
Other monoamines
Peptides

14. Acetylcholine ACh acts on two different types of receptor
Widely used at synapses in the peripheral nervous system.
Released at the terminals of:
all motor neurons activating skeletal muscle.
all preganglionic neurons of the autonomic nervous system
the postganglionic neurons of the parasympathetic branch of the autonomic nervous system.
Also mediates transmission at some synapses in the brain.
include synapses involved in the acquisition of short-term memory.
ACh acts on two different types of receptor

15. ACh Receptors nicotinic receptors are: muscarinic receptors are:
found at the neuromuscular junction of skeletal (only) muscles,
on the post-ganglionic neurons of the parasympathetic nervous system, and
on many neurons in the brain (e.g. in the ventral tegmental area).
nicotine is an agonist (hence the name)
curare is an antagonist (hence its ability to paralyze skeletal muscles)
muscarinic receptors are:
found at the neuromuscular junctions of cardiac and smooth muscle as well as on glands, and on
the post-ganglionic neurons of the sympathetic nervous system.
muscarine (a toxin produced by certain mushrooms) is an agonist.
atropine is an antagonist (hence its use in acetylcholinesterase poisoning)

16. Amino acids Glutamic acid (Glu); Glycine (Gly).
used at excitatory synapses in the CNS.
Essential for long-term potentiation (LTP), a form of memory.
Like GABA, Glu acts on two types of CNS synapses:
FAST (~1 msec) with Glu opening ligand-gated Na+ channels;
SLOW (~1 sec) with Glu binding to receptors that turn on a "second messenger" cascade of biochemical changes that open channels allowing Na+ into the cell.
Glycine (Gly).
Gamma aminobutyric acid (GABA);
used at inhibitory synapses in the CNS

17. Catecholamines Synthesized from tyrosine (Tyr)
Noradrenaline (also called norepinephrine).
Released by postganglionic neurons of the sympathetic branch of the autonomic nervous system.
Also used at certain synapses in the CNS.
Adrenaline/Dopamine
Used at certain synapses in the CNS

18. Other monoamines Serotonin Histamine
also known as 5-hydroxytryptamine or 5HT.
synthesized from tryptophan (Trp).
Histamine
Both of these neurotransmitters are confined to synapses in the brain.

19. Peptides
8 of the 40+ peptides suspected to serve as neurotransmitters in the brain.
first five also serve as hormones.
Vasopressin (ADH)
Oxytocin
Gonadotropin-releasing hormone (GnRH)
Angiotensin II
Cholecystokinin (CCK)
Substance P
Two enkephalins
Met-enkephalin (Tyr-Gly-Gly-Phe-Met)
Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu)

20. Turning Synapses Off
neurotransmitter must be removed from the synaptic cleft to prepare the synapse for the arrival of the next action potential.
two methods are used:
Reuptake:
neurotransmitter is taken back into the synaptic knob of the presynaptic neuron by active transport.
all the neurotransmitters except acetylcholine use this method.
Acetylcholine is removed from the synapse by enzymatic breakdown into inactive fragments.
enzyme used is acetylcholinesterase.
Nerve gases used in warfare (e.g., sarin) and the organophosphate insecticides (e.g., parathion) achieve their effects by inhibiting acetylcholinesterase thus allowing ACh to remain active.
Atropine is used as an antidote because it blocks ACh muscarinic receptors.

21. Drugs and Synapses
Many drugs that alter mental state achieve at least some of their effects by acting at synapses.
GABA Receptors
Catecholamine synapses
Dopamine synapses
Synapses blocking pain signals

22. GABA Receptors The GABAA receptor is a ligand-gated chloride channel.
Activation increases influx of Cl− ions into the postsynaptic cell raising its membrane potential and thus inhibiting it.
Some drugs bind to GABAA receptor & increase the strength of GABA's binding.
Thus enhance the inhibitory effect of GABA in the CNS.
These drugs include:
sedatives like phenobarbital
beverage alcohol (ethanol)
anti-anxiety drugs like Valium, Librium, Halcion (all members of a group called benzodiazepines)

23. Catecholamine synapses
Many anti-depressant drugs interfere with the reuptake of noradrenaline and serotonin from their synapses
thus enhance their action at the synapse.
The antidepressant fluoxetine ("Prozac"), seems to block only the reuptake of serotonin.

24. Dopamine/Adrenaline synapses
One class of dopamine receptor is bound by such drugs as chloropromazine and haloperidol.
Binding of these drugs leads to increased synthesis of dopamine at the synapse
eases some of the symptoms of schizophrenia.

25. Synapses blocking pain signals
The two enkephalins/endorphins are released at synapses on neurons involved in transmitting pain signals back to the brain.
The enkephalins hyperpolarize the postsynaptic membrane thus inhibiting it from transmitting these pain signals.
The ability to perceive pain is vital.
However, faced with massive, chronic, intractable pain, it makes sense to have a system that decreases its own sensitivity.
Enkephalin synapses provide this intrinsic pain suppressing system.

26. Synapses blocking pain signals
Opiates bind to these same receptors thus excellent pain killers.
Heroin, morphine, codeine, methadone
However, are highly addictive.
By binding to enkephalin receptors, they enhance the pain-killing effects of the enkephalins.
If use of the drug ceases, the now relatively insensitive synapses respond less well to the soothing effects of the enkephalins, and the painful symptoms of withdrawal are produced.

27. KETE