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Neurotransmission: Synaptic Transmission, Synthesis, Degradation, and Receptor Types, Study notes of Neurobiology

An in-depth look into the process of synaptic transmission, focusing on the role of neurotransmitters such as acetylcholine, gaba, and dopamine. It covers their synthesis, degradation, and the criteria for classification as neurotransmitters. Additionally, it discusses the differences and similarities between ionotropic and metabotropic neurotransmitter receptors.

What you will learn

  • What are the general steps involved in synaptic transmission?
  • How is Acetylcholine synthesized, packaged, and hydrolyzed?
  • What are the advantages of each type of neurotransmitter receptor?
  • What are the major differences between ionotropic and metabotropic neurotransmitter receptors?

Typology: Study notes

2021/2022

Uploaded on 09/27/2022

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1. Describe the general steps involved in synaptic transmission.
action potential enters pre-synaptic terminal
AP activates voltage dependent calcium channels
Ca2+ ions enter the cell
Increased Intracellular [Ca2+]
binding of vesicles to presynaptic membrane
release of neurotransmitter into synaptic cleft
binding to postsynaptic receptors,
activation of ion gate sodium channels
Post-synaptic potential > AP
Removal from synaptic cleft by enzymatic degradation or re-uptake across the
plasma membrane
2. Describe the synthesis and degradation steps of the following neurotransmitters:
a. Acetylcholine
Synthesized by ChAT
Packaged into vesicles by VAChT
Hydrolysis by acetylcholinesterase into acetate and choline
Shunting into presynaptic terminals by choline transport protein
b. GABA
Synthesized from glutamate by GAD
Packaged by VGAT
Removal from synaptic cleft by high affinity GABA transporter
c. Dopamine
Synthesized by Tyrosine Hydroxylase
Packaged through Vesicular Monoamine Transporter
reuptake by DAT and/or degradation by MAO or CoMT
3. What are the criteria for a specific substance to be classified as a neurotransmitter?
1) synthesized in neuron, 2) stored in nerve terminal, 3) released in quantities sufficient
to affect postsynaptic cell, 4) exogenous application mimics action, 5) mechanism for
removal, 6) the presence and use of specific pharmacological blockers and agonists.
4. What are the major structural and functional similarities and differences between
ionotropic and metabotropic neurotransmitter receptors? What are the advantages of
each? Provide two examples of each type of receptor
STRUCTURAL/FUNCTIONAL SIMILARITIES: Both are transmembrane proteins, both bind
transmitters (ligand gated), both bind transmitter on the extracellular side of the
receptor, and both act as transducers of information from the presynaptic cell.
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1. Describe the general steps involved in synaptic transmission. - action potential enters pre-synaptic terminal - AP activates voltage dependent calcium channels - Ca 2+^ ions enter the cell - Increased Intracellular [Ca 2+] - binding of vesicles to presynaptic membrane - release of neurotransmitter into synaptic cleft - binding to postsynaptic receptors, - activation of ion gate sodium channels - Post-synaptic potential > AP - Removal from synaptic cleft by enzymatic degradation or re -uptake across the plasma membrane 2. Describe the synthesis and degradation steps of the following neurotransmitters : a. Acetylcholine - Synthesized by ChAT - Packaged into vesicles by V ACh T - Hydrolysis by acetylcholinesterase into acetate and choline - Shunting into presynaptic terminals by choline transport protein

b. GABA

  • Synthesized from glutamate by GAD
  • Packaged by VGAT
  • Removal from synaptic cleft by high affinity GABA transporter

c. Dopamine

  • Synthesized by Tyrosine Hydroxylase
  • Packaged through Vesicular Monoamine Transporter
  • reuptake by DAT and/or degradation by MAO or CoMT 3. What are the criteria for a specific substance to be classified as a neurotransmitter?
  1. synthesized in neuron, 2) stored in nerve terminal, 3) released in quantities sufficient to affect postsynaptic cell, 4) exogenous application mimics action, 5) mechanism for removal, 6) the presence and use of specific pharmacological blockers and agonists. 4. What are the major structural and functional similarities and differences between ionotropic and metabotropic neurotransmitter receptors? What are the advantages of each? Provide two examples of each type of receptor

STRUCTURAL/FUNCTIONAL SIMILARITIES: Both are transmembrane proteins, both bind transmitters (ligand gated), both bind transmitter on the extracellular side of the receptor, and both act as transducers of information from the presynaptic cell.

STRUCTURAL/FUNCTIONAL DIFFERENCES:

Ionotropic receptors form an ion channel pore and change shape when they bind to a ligand.

Metabotropic receptors are usually coupled to G-proteins and these G proteins are serpentine (7 transmembrane domains) and do not have an intrinsic channel function; instead they activate second-messenger-mediated and other downstream pathways that cause a change in cellular function of the post- synaptic cell.

ADVANTAGES: Ionotropic receptors generate a faster response than metabotropic receptors, but the responses of the latter are often more long lasting. Metabotropic receptors can also activate a wider range of responses than ionotropic receptors.

5. A group of scientists are working on a neuronal culture with the aim of identifying the effects of GABA and glutamate co-transmission on a post-synaptic cell. They make a number of recordings after stimulating the pre-synaptic neurons at different levels of Chloride ion concentration as shown below.

a) Based on the above recordings what would you note as the main findings from this set of experiments. Hint: GABA and glycine both result in Cl-^ ion influx and their impact on Vm depends on the intracellular Cl- concentration. B. Depending on the Cl− reversal potential (E (^) Cl) relative to the resting Vm of a neuron, GABA co-release may dampen cellular excitability by physically hyperpolarizing

For certain neurons which release neurotransmitters from different pools of vesicles, the Ca 2+^ ion sensitivity differs between the 2 pools of vesicles resulting in a co- transmission with differing amounts of neurotransmitters In many cases the vesicles are in anatomically distinct locations in the presynaptic terminal with one group close to the membrane. Classical neurotransmitters generally are stored in small (approximately 50 nm) clear synaptic vesicles. In contrast, neuropeptide transmitters are stored in large (approximately 100 nm) dense core vesicles. Because peptide transmitters typically are released at a high neuronal firing frequency or in a burst-firing pattern