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Content
Chapter 1: Number and diversity of synapses .....................................................................................2
Chapter 2: Synaptic cell adhesion molecules (SCAMs) .........................................................................3
Chapter 3: Synaptic vesicle exocytosis .................................................................................................6
Structures of synaptic SNARE and SM proteins ................................................................................6
Chapter 4: Calcium control of neurotransmitter release ......................................................................8
Structures of synaptotagmins..........................................................................................................9
Complexins ................................................................................................................................... 11
Chapter 5: Synaptic vesicle endocytosis ............................................................................................ 12
Methods to track endocytosis ....................................................................................................... 12
Clatherin-mediated endocytosis .................................................................................................... 13
Chapter 6: Synaptic vesicle pools ...................................................................................................... 14
The three pool method ................................................................................................................. 15
Chapter 7: Neurotransmitter transporters ........................................................................................ 16
Chapter 8: Postsynaptic density ........................................................................................................ 19
Chapter 9: Synaptic neurotransmitter-gated receptors ..................................................................... 21
Cys-loop receptors ........................................................................................................................ 21
Ionotropic glutamate receptors..................................................................................................... 22
Chapter 10: Electrical neuronal communication ................................................................................ 23
Plasticity of electrical synapses ..................................................................................................... 25
Photoreceptor electrical synapses ................................................................................................. 26
Mechanisms controlling plasticity of AII amacrine cell electrical synapses ..................................... 26
Methods to study the electrical synapse ....................................................................................... 27
Functions of electrical synapses .................................................................................................... 28
Chapter 11: Guest Lecture: translational neuroscience ..................................................................... 28
Chapter 12: The neuromuscular junction .......................................................................................... 32
Chapter 13: Amyotrophic Lateral Sclerosis (ALS) ............................................................................... 37
,Chapter 1: Number and diversity of synapses
Synapse: specialized cell-cell junction that allows neurons to communicate with each other and non-
neuronal target cells (e.g. muscle cells at a neural-muscular junction)
A synapse can be chemical, neurotransmitter based, or electrical, electrically coupled.
neural circuit= multiple neurons linked together by a set of synapses in series.
The diversity is based on neurotransmitter use:
• e.g. glutamate, GABA, glycine, dopamine, acetylcholine, (nor)epinephrine, serotonin, ...
• co-transmission may occur.
The diversity based on postsynaptic response:
• excitatory (e.g. glutamate): postsynaptic depolarization
• inhibitory (e.g. GABA, glycine): postsynaptic hyperpolarization
• Neuromodulators (e.g. dopamine, serotonin): no ionotropic receptors, induce biochemical changes
in postsynaptic neuron.
Diversity based on anatomical location: central versus peripheral synapse (e.g. neuro-muscular
junction, neuro-endocrine junction, autonomous neuro-effector junctions).
Chemical synapses
The chemical synapse has some structural aspects and functional aspects (the molecular
underpinnings of how the synapses actually work).
Synaptic vesicles with NT dock at the active zone of the pre-synaptic nerve ending. The active zone
opposes the PSD of the post-synapse. Upon action potential, the post-synapse depolarizes which
causes a local increase calcium concentration. This leads to exocytosis of vesicles at the active zone
and a NT release. Also endocytosis of NT takes place: The vesicles gets acidified, because of the
electrochemical gradient that occurs, and is essential to allow neurotransmitter re-uptake into the
vesicles in the pre-synapse.
Central synapse: where the axon of a presynaptic neuron contacts the dendrite of a postsynaptic
neuron.
,- Type I = asymmetric synapse: excitatory; mainly on dendrites and dendritic spines
- Type II = symmetric synapse (no dendritic spine): inhibitory: concentrate on cell soma and axonal
initial segment.
Active zone (AZ): specialized region on the presynaptic plasma membrane, where synaptic vesicles
are docked and primed for release; the AZ is aligned with the postsynaptic density (PSD)
Molecular composition of PSD: neurotransmitter receptors, trans-synaptic adhesion molecules,
scaffolding molecules, signal transduction molecules.
Different types of spines: add summary boutons etc.
Chapter 2: Synaptic cell adhesion molecules (SCAMs)
Synaptic junctions are organized by trans-synaptic cell adhesion molecules bridging the synaptic cleft.
Synaptic junctions are organized by trans-synaptic cell adhesion molecules bridging the synaptic cleft.
Synaptic cell adhesion molecules (SCAMs) not only connect pre-and postsynaptic compartments, but
also mediate trans-synaptic recognition and signalling processes that are essential for the
establishment, specification and plasticity of synapses.
Examples of SCAMs:
• neurexins and neuroligins : implicated in schizophrenia and autism.
• Ig-domain proteins e.g. synCAMs
• receptor phosphotyrosine kinases and phosphatases
• leucine-rich repeat proteins
SCAMs function = adhese post- and presynapse so that NT can transfer from the pre- to the post- .
Some part of these molecules are inside the cell and organise vesicles and receptors at the active
zone. Post-synaptically they can anchor the PSD with essential proteins.
Four stages of synapse formation and function:
, I) Contact establishment involves recognition of pre- and postsynaptic neurons; this process may
require heterophilic and homophilic interactions between SCAMs to recognize appropriate synaptic
partners.
II) Recruitment of synaptic vesicles, AZs and PSDs; during this stage, SCAMs regulate physical cell-cell
adhesion and serve as anchor proteins to cluster or recruit receptors or components of the pre- and
postsynaptic signalling machinery.
lll) Functional specification stage: organization of the molecular components of the synapse, resulting
in functionality of the synapse.
IV) Synaptic plasticity: SCAMs may contribute to structural and functional synaptic plasticity in
activity-dependent adaptive events.
Synapses continue to be formed and eliminated during the lifetime of an organism.
Functional domains of SCAMS
The adhesive function of SCAMs is based on a limited number of extracellular domains, often
assembled into repeat units:
- Immunoglobulin (Ig) domains: most frequently bind to other Ig domains; most SCAMs
containing Ig domains also contain fibronectin III (FnIII) domains.
- Cadherin domains: always occur in multiple copies connected by a linker that binds 2-3 Ca2+
ions. Therefore, cadherin mediated interactions are Ca 2+-dependent and often homophilic.
- Lamin A, neurexin, and sex hormone-binding protein (LNS) domains (a.k.a. laminin G-like (LG)
domains).
- Leucine-rich repeats (LRRs).
Neurexin-neuroligin interactions
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