Exam preparation: Molecular and Cellular Neurobiology
Exam date: 25 September 2020
Table of Contents
Lecture 2: Ultrastructure of the mammalian synapse ................................................................................. 2
Lecture 3: Synaptic cell adhesion molecules (SCAMs).............................................................................. 5
Lecture 4: Synaptic vesicle exocytosis ......................................................................................................... 8
Lecture 5: Calcium control of neurotransmitter release ........................................................................... 12
Lecture 6: Synaptic vesicle endocytosis ..................................................................................................... 16
Lecture 7: Synaptic vesicle pools ................................................................................................................ 23
Lecture 8: Neurotransmitter transporters ................................................................................................... 25
Lecture 9: The postsynaptic organization/density ..................................................................................... 29
Lecture 10: Neurotransmitter receptors ...................................................................................................... 32
Lecture 11: Electrical neuronal communication......................................................................................... 36
Lecture 12: The neuromuscular junction (NMJ) ........................................................................................ 43
Lecture 13: Amyotrophic lateral sclerosis (ALS) ....................................................................................... 51
,Lecture 2: Ultrastructure of the mammalian synapse
Synapse: a specialized cell-cell junction that allows for neuronal communication.
Synapses communicate with each other, as well as with other non-neuronal target
cells (e.g. muscle cells).
There are two types of synapses:
1. Chemical synapse à Neurotransmitter-based
2. Electrical synapse (lecture 11 – 13) à Electrically coupled
Neural circuit: multiple neurons linked together, by a set of synapses in series.
Diversity of synapses:
Synapses can be distinguished based on the following properties:
- Neurotransmitter (NT) use (e.g. glutamate, GABA, glycine, etc.)
- Postsynaptic response (excitatory, inhibitory or neuromodulatory)
- Anatomical location (central or peripheral nervous system)
Co-transmission of NTs may occur.
Different postsynaptic responses:
- Excitatory (glutamate) à postsynaptic depolarization (by anions)
- Inhibitory (GABA, glycine) à postsynaptic hyperpolarization (by cations)
- Neuromodulatory (dopamine) à induce biochemical changes in postsynaptic
metabotropic receptors (usually G-protein-coupled receptors).
This lecture (lecture 2) focuses on the structural aspects of chemical synapses.
Overview of synaptic vesicle cycle
2
,General overview of the different structures:
Postsynaptic neuron
- Postsynaptic Density (PSD): region of clustered receptors that bind the
secreted neurotransmitters à leads to activation of receptors (opens to ions) à
leading to a postsynaptic response (depending on the neuron).
Presynaptic neuron
- NTs are pumped into Synaptic Vesicles (SVs) by means of the
Neurotransmitter Transporter (NTT).
o There are two types of NTTs.
After NTTs pump NTs into SVs, an Action Potential can be generated and SVs are
moved to the Active Zone (AZ), by means of Scaffold Proteins. At the active zone
the SVs undergo: Docking, Priming, Fusion. Fusion of the SV with the pre-synaptic
membrane leads to Ca2+ influx and subsequent NT release, into the Synaptic Cleft.
After release of NTs, NTs can be recycled, by means of Clathrin-mediated
Endocytosis. After re-uptake of NTs, SVs are acidified, which fuels the
electrochemical gradient for reuptake of NTs into the SVs, by the NTTs.
• Ultrastructure of the mammalian synapse
Central synapse: Where the axon of a presynaptic neuron contacts the dendrite/cell
body or axon of a postsynaptic neuron.
Type I (asymmetric) synapse: Excitatory synapse, mainly on dendrites and
dendritic spines.
Type II (symmetric) synapse: Inhibitory, mainly on cell soma and axonal initial
segment (not on dendritic spines).
Active Zone (AZ): specialized region within the presynaptic plasma membrane,
where synaptic vesicles are docked and primed for release. The AZ is aligned with
the PSD.
3
, Molecular composition of the PSD: The PSD consists out of NT Receptors,
transsynaptic cell adhesion molecules (SCAMs), scaffolding molecules, signal
transduction molecules.
Boutons: regions in axons and dendrites where synapses are found, either
individually or clustered.
Non-synaptic boutons: Boutons without synapses.
4
Exam date: 25 September 2020
Table of Contents
Lecture 2: Ultrastructure of the mammalian synapse ................................................................................. 2
Lecture 3: Synaptic cell adhesion molecules (SCAMs).............................................................................. 5
Lecture 4: Synaptic vesicle exocytosis ......................................................................................................... 8
Lecture 5: Calcium control of neurotransmitter release ........................................................................... 12
Lecture 6: Synaptic vesicle endocytosis ..................................................................................................... 16
Lecture 7: Synaptic vesicle pools ................................................................................................................ 23
Lecture 8: Neurotransmitter transporters ................................................................................................... 25
Lecture 9: The postsynaptic organization/density ..................................................................................... 29
Lecture 10: Neurotransmitter receptors ...................................................................................................... 32
Lecture 11: Electrical neuronal communication......................................................................................... 36
Lecture 12: The neuromuscular junction (NMJ) ........................................................................................ 43
Lecture 13: Amyotrophic lateral sclerosis (ALS) ....................................................................................... 51
,Lecture 2: Ultrastructure of the mammalian synapse
Synapse: a specialized cell-cell junction that allows for neuronal communication.
Synapses communicate with each other, as well as with other non-neuronal target
cells (e.g. muscle cells).
There are two types of synapses:
1. Chemical synapse à Neurotransmitter-based
2. Electrical synapse (lecture 11 – 13) à Electrically coupled
Neural circuit: multiple neurons linked together, by a set of synapses in series.
Diversity of synapses:
Synapses can be distinguished based on the following properties:
- Neurotransmitter (NT) use (e.g. glutamate, GABA, glycine, etc.)
- Postsynaptic response (excitatory, inhibitory or neuromodulatory)
- Anatomical location (central or peripheral nervous system)
Co-transmission of NTs may occur.
Different postsynaptic responses:
- Excitatory (glutamate) à postsynaptic depolarization (by anions)
- Inhibitory (GABA, glycine) à postsynaptic hyperpolarization (by cations)
- Neuromodulatory (dopamine) à induce biochemical changes in postsynaptic
metabotropic receptors (usually G-protein-coupled receptors).
This lecture (lecture 2) focuses on the structural aspects of chemical synapses.
Overview of synaptic vesicle cycle
2
,General overview of the different structures:
Postsynaptic neuron
- Postsynaptic Density (PSD): region of clustered receptors that bind the
secreted neurotransmitters à leads to activation of receptors (opens to ions) à
leading to a postsynaptic response (depending on the neuron).
Presynaptic neuron
- NTs are pumped into Synaptic Vesicles (SVs) by means of the
Neurotransmitter Transporter (NTT).
o There are two types of NTTs.
After NTTs pump NTs into SVs, an Action Potential can be generated and SVs are
moved to the Active Zone (AZ), by means of Scaffold Proteins. At the active zone
the SVs undergo: Docking, Priming, Fusion. Fusion of the SV with the pre-synaptic
membrane leads to Ca2+ influx and subsequent NT release, into the Synaptic Cleft.
After release of NTs, NTs can be recycled, by means of Clathrin-mediated
Endocytosis. After re-uptake of NTs, SVs are acidified, which fuels the
electrochemical gradient for reuptake of NTs into the SVs, by the NTTs.
• Ultrastructure of the mammalian synapse
Central synapse: Where the axon of a presynaptic neuron contacts the dendrite/cell
body or axon of a postsynaptic neuron.
Type I (asymmetric) synapse: Excitatory synapse, mainly on dendrites and
dendritic spines.
Type II (symmetric) synapse: Inhibitory, mainly on cell soma and axonal initial
segment (not on dendritic spines).
Active Zone (AZ): specialized region within the presynaptic plasma membrane,
where synaptic vesicles are docked and primed for release. The AZ is aligned with
the PSD.
3
, Molecular composition of the PSD: The PSD consists out of NT Receptors,
transsynaptic cell adhesion molecules (SCAMs), scaffolding molecules, signal
transduction molecules.
Boutons: regions in axons and dendrites where synapses are found, either
individually or clustered.
Non-synaptic boutons: Boutons without synapses.
4
