Synaptic Transmission

Symmetrical or Gray's Type 2 synapses

Synapses in which the membrane differentiations are similar in thickness. Typically INHIBITORY synapses.

Asymmetrical or Gray's Type 1 Synapses

Synapses in which the postsynaptic membrane differentiations are THICKER than the presynaptic ones. Usually EXCITATORY synapses.

Synapses

The mechanisms that allow the over 100 billion neurons in the CNS to communicate with each other. 2 Basic Types: electrical chemical

What happens to the synaptic vesicle after it releases the neurotransmitters?

They get recycled from the membrane to form new vesicles via the SYNAPTIC VESICLE CYCLE.

Quantal

increments in which neurotransmitters are stored.

Snare Complex

protein-protein interaction bw the vesicle and the presynaptic plasma membrane. Ca binds to snare complex and catalyzes membrane fusion.

Sequence of events involved in transmission at a chemical synapse

1. Action potential invades the presynaptic terminal. 2. The action potential changes the membrane potential (depolarizes the membrane) and opens the "voltage gated" Ca++ channels. 3. Ca++ ions flow into the terminal down their concentration gradient. 4 High levels of Ca in the terminal allows synaptic vesicles to fuse with the plasma membrane. 5. Vesicles then release their contents (neurotransmitters) into the synaptic cleft. 6. Neurotransmitters diffuse across cleft and bind to receptor molecules in the postsynaptic membrane. 7. Binding induces ion channels to open, allowing ions to flow into the post neuron. 8. The neurotransmitter-induced current flow can then induce or inhibit an action potential in the post neuron. This is the process by which info is transmitted from one neuron to another.

3 types of synapses

1. Axodendritic Synapse: the postsynaptic membrane is a dendrite. 2. Axosomatic synapse: The postsynaptic membrane is the cell body (or soma). 3. Axoaxonic synapse: The postsynaptic membrane is another axon

Botulism

1. Can occur from foods containing clostridium or through wound infections. 2. Toxin is a protease that cleaves snare proteins at NMJ. 3. This disrupts transmitter release and results in weakness and/or paralysis of muscles. 4. Severe cases--> respiratory/visceral motor dysfunction.

Synaptic Vesicle Cycle

1. Fusion of the synaptic vesicles (EXOCYTOSIS) with the membrane increases the surface area of the presynaptic terminal. 2. The extra membrane is quickly recycled back to the cytoplasm (ENDOCYTOSIS) and repackaged with newly synthesized neurotransmitters.

Diseases of the Presynaptic Terminal

1. Myasthenic Syndromes: abnormal transmission at the neuromuscular synapses leads to weakness and fatigability of skeletal muscles. ex. Lambert-Eaton Myasthenis Syndrome (LEMS) is a frequent complication of lung cancer. Pts develope an immune response to Ca++ channels at NMJ and subsequent decreased transmitter release. ex. Botulinum and tetanus toxins affect SNARE proteins involved in vesicle fusion. 2. Congenital Myasthenic Syndromes are genetic disorders that cause muscle weakness by affecting neuromuscular transmission. Generally result from defects in endocytosis at the NMJ resulting in decreased size or # of synaptic vesicles.

Anatomy of Typical Synapse

1. PRESYNAPTIC SIDE of synapse is usually an axon terminal. 2. The terminal typically contains dozens of membrane enclosed spheres--> SYNAPTIC VESICLES where neurotransmitters are stored. 3. SYNAPTIC CLEFT seperates the pre and post-synaptic membranes. Cleft is filled with a matrix of extracellular proteins that help to adhere the pre and postsynaptic membranes. 4. Membrane Differentiations: dense accumalations of protein within the membranes on either side of the cleft. 5. Active Zones: accumulations of proteins along the presynaptic membranes. Contain proteins responsible for "docking" and releasing synaptic vesicles. 6. Transmitter Receptors: accumulations of proteins along the postsynaptic membranes. Referred to as "postsynaptic densities."

The role of Ca++ in neurotansmitter release

1. The amount of neurotransmitter released (quantal amount) is very sensitive to the exact amount of Ca that enters the synaptic terminal. 2. A rise in presynaptic Ca concentration is necessary and sufficient for neurotransmitter release. 3. Ca appears to function in conjunction with numerous synaptic proteins

Tetanus

1. Typically via contamination from puncture wounds that harbor clostridium. 2. Also a protease that cleaves SNARE proteins. 3. Tetanus toxin blocks the release of INHIBITORY transmitters from interneurons of the spinal cord. 4. Causes a loss of synaptic inhibition of spinal motor neurons producing hyper-excitation of skeletal muscles and tonic contractions.

End Plate Potential (EPP)

1. When an intracellular microellectrode is used to record the membrane potential of a muscle, an ACTION POTENTIAL in the presynaptic neuron induces a transient depolariztion in the muscle fiber. 2. This change in membrane potential = EPP 3. If large enough EPP will evoke an action potential in the muscle fiber and cause contraction. 4. EPPs = the synchronized release of MANY synaptic vesicles from the presynaptic neuron, are usually above threshold, cauing an action potential in the muscle cell.

Electrical Synapses

1. permit direct electrical flow bw neurons. 2. Found throughout the nervous system 3. Membranes of the 2 communicating neurons are really close at the synapse. 4. Opposing membranes are linked by GAP JUNCTIONS- specialized intercellular channels bw the presynaptic and postsynaptic neurons. 5. Pores in the channels allow ions and other small molecular weight substances (ATP and messenger molecules) to pass bw the two neurons. 6. Allow ionic current to flow through gap junction from neuron to neuron. 7.Current is usually provided by the presynaptic/upstream neuron (via action potential). 8. Current flows into the postsynaptic/downstream neuron. 9. Flow can be BI-DIRECTIONAL. 10. Current flow is REALLY fast--> instantaneous 11. Used to synchronize electrical activity among populations of neurons. 12. Electrical synapse bw the two membranes allows current to flow thru channels initiating postsynaptic action potential.

Miniature End Plate Potentials (MEPPs)

1. small, spontaneous changes in membrane potential of post neurons w/o presynaptic action potentials. 2. sub-threshold and do not evoke action potentials 3. MEPPS= the release of one synaptic vesicle from the presynaptic neuron, causing subthreshold membrane potentials.

Gap Junctions

1. specialized intercellular channels bw the presynaptic and postsynaptic neurons. 2. Consist of interconnecting protein called connexons that form channels creating electrical continuity bw two cells.

3 experiments confirming Ca role in neurotransmitter secretion

1. using Ca channel blockers: Cadmium- is a substance that chemically blocks calcium channels By injecting Cadmium near the synapse and recording membrane potentials.... Blockage of Ca2+ channels -(via cadmium) eliminates both presynaptic calcium current and ....postsynaptic response 2. Microinjection of Ca into presynaptic terminal: . Microinjection of Ca2+ into presynaptic terminals triggers transmitter release in the absence of presynaptic action potentials Ca2+ injection causes transmitter release from presynaptic neuron even without presynaptic action potential... as seen by membrane potential change in postsynaptic cell 3. Microinjection of BAPTA: a Ca chelator: BAPTA is a calcium chelator or buffer (binds calcium & thereby effectively lowers its concentration) Microinjection of presynaptic BAPTA prevents presynaptic action potential from causing transmitter release Hence... no postsynaptic membrane potential change

Chemical Synapses

1. utilize messenger molecules called neurotransmitters that enable cell-cell communication. 2. Synaptic cleft bw pre and post synaptic neurons. 3. Synaptic vesicles (membrane organelles) found in the presynaptic terminal, containing neurotransmitters whick communicate with the postsynaptic neuron. 4. Neurotransmitters bind with receptors on the postsynaptic membrane and allow ions to flow through the receptor's channel.

Why do we learn about neuromuscular junctions?

Many diseases affect the synaptic terminals and vesicle fusion proteins.

Anaerobic Clostridium Bacteria

Produce potent toxins. Botulinum and tetanus toxins are poisons that affect synaptic transmission.