Neurotransmission

Question 1

Describe the seminal observations that lead to the initial discovery of chemical neurotransmission.

Answer 1

Camillo Golgi
§ “The Golgi Method”
· Developed the silver staining technique that densely stains an entire single neuron (dendrite plus axon branches) used to see nervous tissue under light microscopy
o Santiago Ramon y Cajal
§ “The Neuron Doctrine”
· Provided the conceptual foundation for neuroscience by stating that the neuron is the structural and functional unit of the nervous system
· Santiago used the Golgi Method and it led him to this discovery
o Otto Loewi
§ “Vagus Substance”
§
§ Otto took saline solution from the heart after stimulating its vagus nerve, then transferring the solution to a second heart causing it to slow down
§ This lead to the discovery of acetylcholine (Ach) in which Otto called ‘vagusstoff’
· Ach is released after stimulation of vagus nerve, causing heart rate to slow down

Question 2

Compare electrical versus chemical neurotransmission.

Answer 2

Electrical signal occurs frequently between tightly coupled neurons in a circuit. They are action potentials that synchronize activity between functionally coupled neurons. Chemical is more prevalent in nervous system and they can be excitatory, inhibitory, or modulatory. Signal is carried through neurotransmitters. Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is unidirectional.
Signaling in electrical synapses, in contrast, is virtually instantaneous, and some electrical synapses are bidirectional.
Electrical synapses are also more reliable as they are less likely to be blocked, and they are important for synchronizing the electrical activity of a group of neurons.

Question 3

Describe the basic components of the synapse.

Answer 3

Synthesis (except neuropeptides, all neurotransmitters synthesized in axon terminal; enzymes transported from cell body), storage in vesicles (uses energy from protons going against their conc. gradient; neurotransmitter uses proton pump to enter vesicle), release (triggered by Ca2+; vesicle docks, snare complexes form and pull membranes together, ca binds to synaptotagmin and catalyzes membrane fusion), reception on post, reuptake metabolism or diffusion.

Question 4

Describe the Neuromuscular Junction

Answer 4

At the muscle, the motor axon branches into swellings of synaptic boutons. The axons are myelinated by schwann cells. The boutons lie over the end plate. Each bouton has a mitochondria and synaptic vesicles around active zones where Ach is released

Question 5

Describe the difference between exocytosis and endocytosis, and name 1 protein associated with each.

Answer 5

Endocytosis recycles vesicles and are mediated by clathrin and dynamin. Transmitter release is exocytosis and involves synaptotagmin and synaptobrevin in the presence of calcium

Question 6

Define the mechanisms by which botulism toxin, tetanus, and black widow spider venom disrupt neurotransmission.

Answer 6

Botox disrupts the release of neurotransmitter by disrupting the binding of synaptotagmin and synaptobrevin to the synaptic membrane (paralysis). Tetanus does the same thing but botox is taken up by motor neurons (no ach), and text is taken up by interneurons (no gaba so there is too much output  ridged, spasms). Black widow venom causes all vesicles to fuse independent of Ca and prevents reuptake of precursors so neurotransmitter pool is exhausted.

Question 7

What are MEPPs?

Answer 7

Spontaneous miniature end plate potentials. They occur in the absence of nerve stimulation and release the smallest amount of neurotransmitter possible. Amplitude is not normally distributed or random. Values divisible by the lowest unit were most likely to be observed.

Question 8

Describe 2 disorders associated with disrupted chemical neurotransmission

Answer 8

Lambert-Eaton Myasthenic syndrome (LEMS): antibodies against voltage-gated Ca channels at NMJ leads to decrease in release. Presynaptic, leads to muscle weakness.
Myasthenia Gravis: antibodies against receptors at the NMJ. Double vision, drooping, trouble talking and walking. Postsynaptic