r
Radboud University
MOLECULAR
AND CELLULAR
NEUROBIOLOGY
Summary
Boxtel, S.L. van (Sam)
14-10-2023
,TABLE OF CONTENTS
Background info..............................................................................................................................................6
Background info..............................................................................................................................................6
Molecular mechanisms of neuronal communication................................................................................7
Molecular mechanisms of neuronal communication................................................................................7
Synaptic cell adhesion molecules.................................................................................................................9
Synaptic cell adhesion molecules.................................................................................................................9
Synaptic vesicle exocytosis..........................................................................................................................11
Synaptic vesicle exocytosis..........................................................................................................................11
Calcium control of neurotransmitter release...........................................................................................14
Calcium control of neurotransmitter release...........................................................................................14
Synaptic vesicle endocytosis.......................................................................................................................15
Synaptic vesicle endocytosis.......................................................................................................................15
Synaptic vesicle pools...................................................................................................................................19
Synaptic vesicle pools...................................................................................................................................19
Vesicular and plasmamembrane NT transporters..................................................................................20
Vesicular and plasmamembrane NT transporters..................................................................................20
Postsynaptic organization of synapses.....................................................................................................22
Postsynaptic organization of synapses.....................................................................................................22
Synaptic neurotransmitter-gated receptors.............................................................................................23
Synaptic neurotransmitter-gated receptors.............................................................................................23
Electrical neuronal communication...........................................................................................................25
Electrical neuronal communication...........................................................................................................25
Neuromuscular junction..............................................................................................................................29
Neuromuscular junction..............................................................................................................................29
Amyotrophic Lateral Sclerosis (ALS)...........................................................................................................35
Amyotrophic Lateral Sclerosis (ALS)...........................................................................................................35
Tiesinga lecture.............................................................................................................................................37
Tiesinga lecture.............................................................................................................................................37
Simulated research project.........................................................................................................................40
Simulated research project.........................................................................................................................40
Quiz.................................................................................................................................................................47
Quiz.................................................................................................................................................................47
,Which neurotransmitters are neuromodulatory? And which are inhibitory or excitatory?..........47
Which neurotransmitters are neuromodulatory? And which are inhibitory or excitatory?..........47
Deduce the different functions of cell adhesion molecules at synapses.........................................47
Deduce the different functions of cell adhesion molecules at synapses.........................................47
Describe the different stages of synapse formation and funciton, and the role of SCAMs in each
of these stages...........................................................................................................................................47
Describe the different stages of synapse formation and funciton, and the role of SCAMs in each
of these stages...........................................................................................................................................47
Give examples of SCAMs and their funcitonal domains.....................................................................47
Give examples of SCAMs and their funcitonal domains.....................................................................47
Schematically draw SCAMs to illustrate how they function...............................................................47
Schematically draw SCAMs to illustrate how they function...............................................................47
Explain what SNARE proteins are, and which SNARE proteins are involved in synaptic vesicle
exocytosis...................................................................................................................................................47
Explain what SNARE proteins are, and which SNARE proteins are involved in synaptic vesicle
exocytosis...................................................................................................................................................47
Schematically draw the functional domains of the SNARE proteins involved in SV exocytosis, as
well as the assemble SNARE complex....................................................................................................47
Schematically draw the functional domains of the SNARE proteins involved in SV exocytosis, as
well as the assemble SNARE complex....................................................................................................47
Describe the SNARE/SM protein cycle...................................................................................................48
Describe the SNARE/SM protein cycle...................................................................................................48
Describe how chaperones support SNARE protein function, and explain how their dysfunction
results in neurodegeneration..................................................................................................................48
Describe how chaperones support SNARE protein function, and explain how their dysfunction
results in neurodegeneration..................................................................................................................48
Explain the mechanisms by which calcium controls neurotransmitter release.............................48
Explain the mechanisms by which calcium controls neurotransmitter release.............................48
Describe the structure of the three groups of synaptotagmins........................................................48
Describe the structure of the three groups of synaptotagmins........................................................48
Explain which synaptotagmins function as synaptic calcium sensors for neurotransmitter
release and how this has been discovered and demonstrated........................................................48
Explain which synaptotagmins function as synaptic calcium sensors for neurotransmitter
release and how this has been discovered and demonstrated........................................................48
Explain how complexin and synaptotagmin function together to mediate calcium-induced
synaptic vesicle exocytosis......................................................................................................................48
, Explain how complexin and synaptotagmin function together to mediate calcium-induced
synaptic vesicle exocytosis......................................................................................................................48
Describe the events that occur between an incoming action potential at the presynaptic
terminal and synaptic vesicle exocytosis...............................................................................................48
Describe the events that occur between an incoming action potential at the presynaptic
terminal and synaptic vesicle exocytosis...............................................................................................48
Describe the different endocytic pathways that can be used for synaptic vesicel recycling........48
Describe the different endocytic pathways that can be used for synaptic vesicel recycling........48
Explain the methods that can be used to study sV endocytosis and infer which method is best
sutied for a given experimental quesiton.............................................................................................48
Explain the methods that can be used to study sV endocytosis and infer which method is best
sutied for a given experimental quesiton.............................................................................................48
List the sequential steps of clathrin-mediated endocytosis, the different classes of molecules
involved, and give examples of molecuels............................................................................................49
List the sequential steps of clathrin-mediated endocytosis, the different classes of molecules
involved, and give examples of molecuels............................................................................................49
Describe three pool models and how they function...........................................................................49
Describe three pool models and how they function...........................................................................49
Explain the methods to study synaptic vesicle pools and apply to a given scientific question....49
Explain the methods to study synaptic vesicle pools and apply to a given scientific question....49
Name the classical vesicular and plasmamembrane NT transporters.............................................49
Name the classical vesicular and plasmamembrane NT transporters.............................................49
Explain how nT transporters function, including their driving forces and their role in
neurotransmitter cycle.............................................................................................................................49
Explain how nT transporters function, including their driving forces and their role in
neurotransmitter cycle.............................................................................................................................49
Infer how NT transporters can modulate synaptic strength..............................................................49
Infer how NT transporters can modulate synaptic strength..............................................................49
Explain the effects of drugs that act on plasma membrane NT transporters (PMNTTs) and how
genetic mutation in PMNTTs may lead to disease...............................................................................50
Explain the effects of drugs that act on plasma membrane NT transporters (PMNTTs) and how
genetic mutation in PMNTTs may lead to disease...............................................................................50
How is it possible that vesicular neurotransmitter transporters are able to pump
neurotransmitters from the cytoplasm (where neurotransmitter concentration is relatively low)
into the synaptic vesicles (where neurotransmitter concentration is high)? What fuels this
process?......................................................................................................................................................50
Radboud University
MOLECULAR
AND CELLULAR
NEUROBIOLOGY
Summary
Boxtel, S.L. van (Sam)
14-10-2023
,TABLE OF CONTENTS
Background info..............................................................................................................................................6
Background info..............................................................................................................................................6
Molecular mechanisms of neuronal communication................................................................................7
Molecular mechanisms of neuronal communication................................................................................7
Synaptic cell adhesion molecules.................................................................................................................9
Synaptic cell adhesion molecules.................................................................................................................9
Synaptic vesicle exocytosis..........................................................................................................................11
Synaptic vesicle exocytosis..........................................................................................................................11
Calcium control of neurotransmitter release...........................................................................................14
Calcium control of neurotransmitter release...........................................................................................14
Synaptic vesicle endocytosis.......................................................................................................................15
Synaptic vesicle endocytosis.......................................................................................................................15
Synaptic vesicle pools...................................................................................................................................19
Synaptic vesicle pools...................................................................................................................................19
Vesicular and plasmamembrane NT transporters..................................................................................20
Vesicular and plasmamembrane NT transporters..................................................................................20
Postsynaptic organization of synapses.....................................................................................................22
Postsynaptic organization of synapses.....................................................................................................22
Synaptic neurotransmitter-gated receptors.............................................................................................23
Synaptic neurotransmitter-gated receptors.............................................................................................23
Electrical neuronal communication...........................................................................................................25
Electrical neuronal communication...........................................................................................................25
Neuromuscular junction..............................................................................................................................29
Neuromuscular junction..............................................................................................................................29
Amyotrophic Lateral Sclerosis (ALS)...........................................................................................................35
Amyotrophic Lateral Sclerosis (ALS)...........................................................................................................35
Tiesinga lecture.............................................................................................................................................37
Tiesinga lecture.............................................................................................................................................37
Simulated research project.........................................................................................................................40
Simulated research project.........................................................................................................................40
Quiz.................................................................................................................................................................47
Quiz.................................................................................................................................................................47
,Which neurotransmitters are neuromodulatory? And which are inhibitory or excitatory?..........47
Which neurotransmitters are neuromodulatory? And which are inhibitory or excitatory?..........47
Deduce the different functions of cell adhesion molecules at synapses.........................................47
Deduce the different functions of cell adhesion molecules at synapses.........................................47
Describe the different stages of synapse formation and funciton, and the role of SCAMs in each
of these stages...........................................................................................................................................47
Describe the different stages of synapse formation and funciton, and the role of SCAMs in each
of these stages...........................................................................................................................................47
Give examples of SCAMs and their funcitonal domains.....................................................................47
Give examples of SCAMs and their funcitonal domains.....................................................................47
Schematically draw SCAMs to illustrate how they function...............................................................47
Schematically draw SCAMs to illustrate how they function...............................................................47
Explain what SNARE proteins are, and which SNARE proteins are involved in synaptic vesicle
exocytosis...................................................................................................................................................47
Explain what SNARE proteins are, and which SNARE proteins are involved in synaptic vesicle
exocytosis...................................................................................................................................................47
Schematically draw the functional domains of the SNARE proteins involved in SV exocytosis, as
well as the assemble SNARE complex....................................................................................................47
Schematically draw the functional domains of the SNARE proteins involved in SV exocytosis, as
well as the assemble SNARE complex....................................................................................................47
Describe the SNARE/SM protein cycle...................................................................................................48
Describe the SNARE/SM protein cycle...................................................................................................48
Describe how chaperones support SNARE protein function, and explain how their dysfunction
results in neurodegeneration..................................................................................................................48
Describe how chaperones support SNARE protein function, and explain how their dysfunction
results in neurodegeneration..................................................................................................................48
Explain the mechanisms by which calcium controls neurotransmitter release.............................48
Explain the mechanisms by which calcium controls neurotransmitter release.............................48
Describe the structure of the three groups of synaptotagmins........................................................48
Describe the structure of the three groups of synaptotagmins........................................................48
Explain which synaptotagmins function as synaptic calcium sensors for neurotransmitter
release and how this has been discovered and demonstrated........................................................48
Explain which synaptotagmins function as synaptic calcium sensors for neurotransmitter
release and how this has been discovered and demonstrated........................................................48
Explain how complexin and synaptotagmin function together to mediate calcium-induced
synaptic vesicle exocytosis......................................................................................................................48
, Explain how complexin and synaptotagmin function together to mediate calcium-induced
synaptic vesicle exocytosis......................................................................................................................48
Describe the events that occur between an incoming action potential at the presynaptic
terminal and synaptic vesicle exocytosis...............................................................................................48
Describe the events that occur between an incoming action potential at the presynaptic
terminal and synaptic vesicle exocytosis...............................................................................................48
Describe the different endocytic pathways that can be used for synaptic vesicel recycling........48
Describe the different endocytic pathways that can be used for synaptic vesicel recycling........48
Explain the methods that can be used to study sV endocytosis and infer which method is best
sutied for a given experimental quesiton.............................................................................................48
Explain the methods that can be used to study sV endocytosis and infer which method is best
sutied for a given experimental quesiton.............................................................................................48
List the sequential steps of clathrin-mediated endocytosis, the different classes of molecules
involved, and give examples of molecuels............................................................................................49
List the sequential steps of clathrin-mediated endocytosis, the different classes of molecules
involved, and give examples of molecuels............................................................................................49
Describe three pool models and how they function...........................................................................49
Describe three pool models and how they function...........................................................................49
Explain the methods to study synaptic vesicle pools and apply to a given scientific question....49
Explain the methods to study synaptic vesicle pools and apply to a given scientific question....49
Name the classical vesicular and plasmamembrane NT transporters.............................................49
Name the classical vesicular and plasmamembrane NT transporters.............................................49
Explain how nT transporters function, including their driving forces and their role in
neurotransmitter cycle.............................................................................................................................49
Explain how nT transporters function, including their driving forces and their role in
neurotransmitter cycle.............................................................................................................................49
Infer how NT transporters can modulate synaptic strength..............................................................49
Infer how NT transporters can modulate synaptic strength..............................................................49
Explain the effects of drugs that act on plasma membrane NT transporters (PMNTTs) and how
genetic mutation in PMNTTs may lead to disease...............................................................................50
Explain the effects of drugs that act on plasma membrane NT transporters (PMNTTs) and how
genetic mutation in PMNTTs may lead to disease...............................................................................50
How is it possible that vesicular neurotransmitter transporters are able to pump
neurotransmitters from the cytoplasm (where neurotransmitter concentration is relatively low)
into the synaptic vesicles (where neurotransmitter concentration is high)? What fuels this
process?......................................................................................................................................................50
