4. synaptic transmission

8/7/2019 4. synaptic transmission

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Faculty of Medicine

Dr Zad Mansour

Synaptic Transmission


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Synaptic transmission: The information travels in synapses

Described by Sherrington in 1897

Chemical transmission:

Otto Loewi and Vagusstoff

In the night of Easter Sunday, 1921, I awoke, turned on the light, and jotted down afew notes on a tiny slip of paper. Then, I fell asleep again.

It occurred to me at six o'clock in the morning that during the night I had writtendown something most important.


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Synapse:

Is the specialized junction where one part of a neuron contacts and communicates withanother neuron or cell type (muscle or gland).

Electrical synapses:

Six connexin subunits comprise

one connexon,

two connexons comprise

one gap junction channel,

and many gap junction channels

comprise one gap junction


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Synaptic integration:

several PSPs occur simultaneously and induce an action potential


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Chemical synapse:

-Most synaptic transmission is chemical

-Synaptic cleft between pre- and post synaptic neurons

-Membrane differentiations: dense accumulations of protein adjacent to and withinthe membranes on either side of the synaptic cleft.

-Active zones: are the actual sites of NT release.


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(a) An axodendritic synapse (b) An axosomatic synapse (c) An axoaxonic synapse.


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(a) A Gray's type I synapse is asymmetrical and usually excitatory.

(b) A Gray's type II synapse is symmetrical and usually inhibitory.


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Principles of chemical synaptic transmission:

-Mechanism for synthesizing NT and packing it into the synaptic vesicles

-Mechanism for causing vesicles to spill their contents into the synaptic cleft inresponse to a presynaptic action potential

-Mechanism for producing an electrical or biochemical response to NT in thepostsynaptic neuron

-Mechanism for removing NT from the synaptic cleft

The major NT:


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Different neurons in the brain release different neurotransmitters.

Fast synaptic transmission at most CNS synapses is mediated by the amino acidsglutamate (Glu), gamma-amino butyric acid (GABA), and glycine (Gly).

The amine acetylcholine (ACh) mediates fast synaptic transmission at allneuromuscular junctions.


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The synthesis and storage of different types of neurotransmitter(a) Peptides: 1. A precursor peptide is synthesized in the rough ER. 2. The precursor peptide is

split in the Golgi apparatus to yield the active neurotransmitter. 3. Secretory vesiclescontaining the peptide bud off from the Golgi apparatus. 4. The secretory granules aretransported down the axon to the terninal where the peptide is stored.

(b) Amine and amino acid neuroransmitters: 1. Enzymes convert precursor molecules Intoneurotransmitter molecules in the cytosol. 2. Transporter proteins load the neurotransmitter

into synaptic vesicles in the terminal, where they are stored.


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The release of neurotransmitter by exocytosis.1. A synaptic vesicle loaded with neurotransmitter, in response to 2. an influx ofCa2+ through voltage-gated calcium channels. 3. releases its contents into thesynaptic cleft by the fusion of the vesicle membrane with the presynaptic

membrane, and 4. is eventually recycled by the process of endocytosis.


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Neurotransmitter receptors:

1. Transmitter-gated ion channels

2. G protein-coupled receptors

Transmitter-gated ion channels

Synaptic activation of ACh- gated andglutamate-gated ion channels causes EPSPs.

Synaptic activation of glycine-gated or GABA-

gated ion channels cause an IPSP.


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G protein-coupled receptors (metabotropic receptors):

1. Neurotransmitter molecules bind to receptor proteins embedded in the postsynapticmembrane.

2. The receptor proteins activate small proteins, called G-proteins, that are free tomove along the intracellular face of the postsynaptic membrane.

3. The activated G-proteins activate "effector" proteins.

- The same neurotransmitter can have different postsynaptic actions, depending onwhat receptors it binds to.

- The effect of ACh on the heart and on skeletal muscles.


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Autoreceptors:

- Presynaptic receptors that are sensitive to the neurotransmitter released by thepresynaptic terminal are called autoreceptors.

- Autoreceptors are G-protein-coupled receptors that stimulate second messengerformation.

- Activation of these receptors results in inhibition of neurotransmitter release andneurotransmitter synthesis.

- This allows a presynaptic terminal to regulate itself.

- Autoreceptors appear to function as a sort of safety valve to reduce release whenthe concentration of neurotransmitter in the synaptic cleft gets too high.


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Neurotransmitter recovery

-Reuptake of NT into the presynaptic axon terminal

-NT enzymatic destruction in the synaptic cleft

-Clostridium botulinum:

It destroys certain proteins in the presynaptic terminal which are critical fortransmitter release.

-black widow:

Its venom binds to protein on the outside of the presynaptic membrane and triggersrapid and total depletion of transmitter

-Cobra:

Its venom binds to and blocks the postsynaptic nicotinic ACh receptors

-Organophosphates:

Irreversible inhibitors of AChE.


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-Receptor antagonists:

Curare binds tightly to ACh receptors on skeletal muscle cells and blocks the action

of ACh, thereby preventing muscle contraction.

-Receptor agonists:

Bind to receptors and mimic the action of natural NT

Nicotinic ACh receptors in the CNS


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Synaptic integration:

The process by which multiple synaptic potentials combine within one postsynaptic

neuron.The transformation of many synaptic inputs to a single neuronal output constitutes aneural computation.

Quantal analysis of EPSPs:

postsynaptic EPSPs at a given synapse are quantized; they are multiples of anindivisible unit, the quantum, that reflects the number of transmitter molecules in asingle synaptic vesicle and the number of postsynaptic receptors available at thesynapse.


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EPSP summation:

Is the simplest form of synaptic integration in the CNS

Spatial and temporal summation.

Spatial summation: is the adding together of EPSPs generated simultaneously at manydifferent synapses on a dendrite.

Temporal summation: is the adding together of EPSPs generated at the same synapse

if they occur in rapid succession, within about 1-15 msec of one another


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IPSPs and shunting inhibition:


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Modulation:

Modulation by the NE preceptor

1) The binding of NE to the receptor activates a G-protein in the membrane.

2) The G- protein activates the enzyme adenylyl cyclase.

3) Adenylyl cyclase converts ATP into the second messenger cAMP

4) cAMP activates a protein kinase.

5) The protein kinase causes a potassium channel to close by attaching a phosphate group to it.

6) This increases the response produced by another NT at an excitatory synapse.

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4. synaptic transmission