Ch 5: Synaptic Transmission

Define synaptic transmission.

The process of information transfer at a synapse

What is the contribution of Charles Sherrington?

Gave synapses their name

What is the contribution of Otto Loewi?

Did experiments with frogs to provide support for the concept of chemical synapses.

What is the contribution of Furshpan and Potter?

Proved the existence of electrical synapses through experimentation on the nervous systems of crayfish.

Describe a presynaptic cell in a general synapse.

The first neuron in synaptic transmission

Describe a postsynaptic cell in a general synapse.

The target cell in synaptic transmission

Describe a presynaptic cell in the NMJ.

The presynaptic terminal of a motor axon

Describe a postsynaptic cell in the NMJ.

The motor endplate, which contains shallow folds where the presynaptic active zones precisely align with

Describe the structure for a gap junction.

• The membranes of two cells are ~3nm apart

• ConnexINs (clusters of specialized proteins span the gap)

• Six connexIN subunits combine to form a channel called a connexON

• Two connexONs (one from each cell) meet and combine to form a gap junction channel

What is the function of the gap junction channel?

It allows ions to pass directly from the cytoplasm of one cell to the cytoplasm of another cell

How large are the pore of most gap junction channels and why is this relevant?

• 1-2 nm

• It is large enough for all the major cellular ions and many small organic molecules to pass through

Describe the synaptic transmission for a gap junction.

• Synaptic transmission occurs via electrical current

• Cells connected by gap junctions are said to be electrically coupled

• An action potential in the presynaptic neuron causes a small amount of ionic current to flow across the gap junction channels into the other neuron

• Ionic current causes an electrically mediated postsynaptic potential (PSP) in the second neuron

• Most electrical synapses are bidirectional → the generation of an action potential in the second neuron can in turn induce a PSP in the first neuron

• It may take multiple PSPs occurring simultaneously to strongly excite a neuron AKA synaptic integration

Describe directionality for a gap junction.

Synaptic transmission is bidirectional due to electrical current

Describe the 7 steps of chemical synaptic transmission.

1. Presynaptic cell synthesizes neurotransmitter

2. Presynaptic cell loads neurotransmitter into synaptic vesicles

3. Vesicles fuse/undergo exocytosis to presynaptic cleft

4. Neurotransmitter spills into synaptic cleft

5. Neurotransmitter binds to postsynaptic receptors

6. Biochemical/electrical response elicited in postsynaptic cell

7. Leftover neurotransmitter is removed from the synaptic cleft

Describe the 5 types of CNS chemical synapses.

1. Axodendritic: axon to dendrite

2. Axosomatic: axon to cell body (soma)

3. Axoaxonic: axon to axon

4. Axospinous: Axon to dendritic spine

5. Dendrodendritic: dendrite to dendrite

Describe the structure for an NMJ.

• occurs between the axons of motor neurons of the spinal cord and skeletal muscle

• presynaptic terminal contains a large number of active zones

• postsynaptic membrane/motor endplate has folds that contain neurotransmitter receptors

• This structure ensures that many neurotransmitter molecules are focally released onto a large surface of chemically sensitive membrane

Describe the synaptic transmission for an NMJ.

• fast and reliable

• an action potential in the motor axon always causes an action potential in the muscle it innervates

Describe directionality for an NMJ.

Neuron to axon to muscle

Describe the 3 types of neurotransmitters and how they are packaged.

1. Amines → stored in synaptic vesicles

2. Amino acids → stored in synaptic vesicles

3. Peptides → stored in secretory granules

Describe neurotransmitter synthesis and storage for peptides.

1. A long peptide is synthesized in the rough ER

2. Peptide is split in the Golgi apparatus

3. One of the smaller peptide fragments is the active neurotransmitter

4. Secretory granules containing the peptide neurotransmitter bud off from the Golgi apparatus

5. Those secretory granules are transported to the axon terminal via axoplasmic transport

Describe neurotransmitter synthesis and storage for amino acids and amines.

1. Neurons contain specific enzymes that synthesize the neurotransmitters from various metabolic precursors

2. The synthesizing enzymes for both amine and amino acid neurotransmitters are transported to the axon terminal

3. Enzymes locally and rapidly direct neurotransmitter synthesis in the cytosol of the axon terminal

4. Neurotransmitters are packed into synaptic vesicles via transporters (special proteins embedded into the vesicle membrane)

Describe the 4 steps of neurotransmitter release.

1. Vesicle full of neurotransmitter is docked and primed

2. Intracellular calcium triggers exocytosis of the neurotransmitter

3. Vesicle membrane is incorporated into presynaptic membrane and neurotransmitter is released into the cleft

4. Vesicle membrane is recovered by endocytosis

Describe the role of calcium in vesicle fusion.

Calcium binds to synaptotagmin to induce docking of the vesicle to the presynaptic membrane

Describe the role of in synaptotagmin in vesicle fusion.

It is a vesicle protein that sense to Ca2+ to trigger vesicle fusion and neurotransmitter release

Describe the role of v-SNARES and t-SNARES in vesicle fusion.

• V-SNARES on the vesicle bind to t-SNARES on the presynaptic terminal membrane

• The cytosolic ends of these SNAREs bind very tightly to one another

  • Allows a vesicle to dock very close to a presynaptic membrane

Describe the role of clathrin in vesicle endocytosis.

• A protein that binds to the membrane → causes a conformational change to the membrane to form a “soccerball” vesicle

Describe the role of dynamin in vesicle endocytosis.

Pinches the vesicle off from the membrane

Describe 4 ways neurotransmitter can be removed from the synaptic cleft.

1. Diffusion of transmitter molecules away form the synapse

2. Reuptake: NT reenters presynaptic axon terminal

3. Enzymatic destruction (i.e. acetylcholinesterase) inside the terminal cytosol or synaptic cleft

4. Desensitization: Receptors become insensitive to NT, despite the presence of NT

Describe the cycle of acteylcholine.

1. Neurons release vesicles with acetylcholine

2. ACh goes into synaptic cleft and binds to ACh receptors in the postsynaptic cell.

3. AChE in the synaptic cleft degrades ACh into choline and acetic acid

4. Choline is reuptaken back into the presynaptic cell via a cotransporter → transports both choline and Na+

5. Choline and Acetyl CoA add together in a chemical reaction catalyzed by choline acetyltransferase (ChAT) to make ACh

6. ACh is transported into vesicles awaiting exocytosis

Describe the action of the acetylcholine receptor.

Receives ACh from the postsynaptic cleft

Describe the location and role of an autoreceptor.

• Presynaptic receptors that are sensitive to the neurotransmitter released by the presynaptic terminal

• Located on the presynaptic axon terminal

• Functions on negative feedback

  • Autoreceptor senses release of NT and therefore inhibits further release of NT

Define agonist.

Mimics the action of naturally occurring neurotransmitters

Define antagonist.

Inhibits neurotransmitter receptors

Describe the source and action of alpha bungarotoxin.

• From cobra snake

• Blocks the AChR channel in a closed position = paralysis (muscle cannot contract)

Describe the source and action of curare.

• Naturally occurring poison from plants

• Binds and blocks AChR channels from opening

• Only prevents movement, needs to be used with an analgesic to numb pain

Describe the source and action of organophosphates.

• DTT & herbicides are insecticides (malathion, parathion)

• Inhibit AChE → ACh accumulates in the synaptic cleft → AChR becomes desensitized → inability to contract muscles

Describe the source and action of latrotoxin

• Produced by the female black widow spider

• Causes depletion of synaptic vesicles by stimulating mass exocytosis of of vesicles dependent of calcium increase

Describe the source and action of botulinum toxin.

• From Clostridium bacteria

• Protease that cleaves the core SNARE complex proteins used for vesicle fusion → prevents vesicles form docking → prevents exocytosis

Describe the source and action of tetanus.

• From Clostridium bacteria

• Protease that cleaves the core SNARE complex proteins used for vesicle fusion → prevents vesicles form docking → prevents exocytosis

Define EPSP.

• Excitatory postsynaptic potential

• Presynaptic neurotransmitter release → transient postsynaptic membrane depolarization

Define IPSP.

• Inhibitory postsynaptic potential

• Presynaptic neurotransmitter release → transient postsynaptic membrane hyperpolarization

Define presynaptic facilitation.

Increase in the amount of neurotransmitter released from postsynaptic neuron

Define quantal analysis.

• Used to determine numbers of vesicles that release during neurotransmission

• We cannot measure a single neurotransmitter, but we can measure a single vesicle

Define temporal summation.

EPSPs generated at same synapse in rapid succession

Define spatial summation.

EPSPs generated simultaneous at different sites

Define dendritic length constant.

The distance that a postsynaptic potential can spread along the membrane until it reaches 37% of origin

Define internal resistance.

The resistance to current flowing longitudinally down the dendrite (dependent on diameter)

Define membrane resistance.

Explain how the dendritic length constant changes if the internal resistance increases.

Dendritic length constant increases as membrane potential increases

Explain how the dendritic length constant changes if the diameter increases.

Dendritic length constant decreases as internal resistance/diameter increases

Explain how the dendritic length constant changes if the membrane resistance increases.

Explain how the dendritic length constant changes if more channels are open.

Explain shunting inhibition.

Explain modulation.