The document discusses synapses, the connections between neurons that allow neuronal communication. It begins by discussing the history and etymology of the term "synapse", which was coined in 1897. It then defines synapses and describes their basic anatomical components. The rest of the document classifies synapses based on various properties like location, effect, basis of process, transmitter, and junction type. It also discusses the synaptic vesicle cycle of trafficking neurotransmitters and fusing with the neuronal membrane. Debate around different modes of vesicle fusion like "kiss-and-run" is also summarized.

1. Synapse
what, where, when, how, ???
Hoseinpourfard M. PhD Student
Institute Cognitive Sciences Studies, Tehran, Iran.
2015 Jan 15

2. Joseph Le Doux, 2002 (in Synaptic Self)
 "You are your synapses. They are who you are."

3. SYNAPSE’s Birthday
 In 2014, the word "synapse" turned 117 years old. The word synapse
was first used in a book called A Textbook of Physiology, part three:
The Central Nervous System, by Michael Foster and assisted by
Charles S. Sherrington, in 1897. It was probably Charles S. Sherrington
who coined the term synapse. The word "synapse" is derived from
the Greek words "syn" and "haptein" that mean "together" and "to
clasp,".

4. What is the synapse
Information from one neuron flows to another neuron across a synapse.
The synapse contains a small gap separating neurons.(1) It is a
structure that permits a neuron to pass an electrical or chemical signal
to another cell (neural or otherwise)(2)
The synapse consists of:
1.a presynaptic ending that contains neurotransmitters, mitochondria
and other cell organelles
2.a postsynaptic ending that contains receptor sites for
neurotransmitters
3.a synaptic cleft or space between the presynaptic and postsynaptic
endings.(1)

5. Classification of synapses
 By location
 By effect
 By basis of process
 By transmitter
 By junction tissue

6. Classification of synapses
 By basis of process:
1. electrical,
2. chemical,
3. and electro-chemical

7. Classification of synapses
 By effect:
 excitory,
 inhibitory

8. Classification of synapses
 By transmitter:
1. Esters
 Acetylcholine
2. Monoamines
 Norepinephrine
 Dopamine
 Serotonin
3. Amino Acids
 GABA
 Glutamate
4. Purines
 Enkephaline
 Substance P
5. Inorganic Gases
 NO
 an electrical impulse will trigger the
migration of vesicles (the red dots in
the figure to the left) containing
neurotransmitters toward the
presynaptic membrane. The vesicle
membrane will fuse with the
presynaptic membrane releasing
the neurotransmitters into the
synaptic cleft. Until recently, it was
thought that a neuron produced
and released only one type of
neurotransmitter. This was called
"Dale's Law.” However, there is now
evidence that neurons can contain
and release more than one kind of
neurotransmitter.

9. Classification of synapses
 By junction:
 Neuron – Neuron
 Neuron – Skeletal muscle fibers
 Neuron – Gland cells

10. Classification of synapses
 By location:
Axo-Somatic
Axo-Dendrityc
Axo-Axonic

12. Taxonomy of Synapse
 Tsoi and Back's taxonomy is composed of four dimensions:
1. synapse type (which can assume a value of simple or dynamic),
2. synapse feedback (which can be yes or no),
3. activation feedback (which can be yes or no),
4. and output feedback (which can be yes or no
My Suggestion: Properties, Status, and Behavior like (Object Oriented)
Kremer, Stefan C. "Spatiotemporal connectionist networks: A taxonomy
and review." Neural Computation 13, no. 2 (2001): 249-306.

13.  For communication between
neurons to occur, an electrical
impulse must travel down an axon
to the synaptic terminal
1. Electrical Trigger for
Neurotransmission
2. Neurotransmitter Mobilization and
Release

14.  When a neurotransmitter binds to a receptor on the postsynaptic
side of the synapse, it changes the postsynaptic cell's excitability: it
makes the postsynaptic cell either more or less likely to fire an action
potential. If the number of excitatory postsynaptic events is large
enough, they will add to cause an action potential in the
postsynaptic cell and a continuation of the "message."

17. The synapse and synaptic vesicle cycle

18. The synaptic vesicle cycle
 1. Trafficking to the synapse
 2. Transmitter loading
 3. Docking
 4. Priming
 5. Fusion
 6. Exocytosis
 7. Endocytosis
 8. Auto Regulation

19. 1. Trafficking to the synapse
 Synaptic vesicle components
are initially trafficked to the
synapse using members like a
orchestra symphony.
(rezayof,2014)

20. 2. Transmitter loading
 Once at the synapse, synaptic
vesicles are loaded with a
neurotransmitter. Loading of
transmitter is an active process
requiring a neurotransmitter
transporter and a proton pump
ATPase that provides an
electrochemical gradient
(glutamate – NaK-ATPase).
These transporters are selective
for different classes of
transmitters.

21. 3. Docking
 The loaded synaptic vesicles must
dock near release sites, however
docking is a step of the cycle that
we know little about. Many proteins
on synaptic vesicles and at release
sites have been identified, however
none of the identified protein
interactions between the vesicle
proteins and release site proteins
can account for the docking phase
of the cycle. Mutants in rab-3 and
unc-18 alter vesicle docking or
vesicle organization at release sites,
but they do not completely disrupt
docking.[26] SNARE proteins, do not
appear to be involved in the
docking step of the cycle.

22. 4. Priming
 Priming prepares the synaptic
vesicle so that they are able to
fuse rapidly in response to a
calcium influx. This priming step is
thought to involve the formation of
partially assembled SNARE
complexes. The proteins Munc13,
RIM, and RIM-BP participate in this
event. [27] Munc13 is thought to
stimulate the change of the t-
SNARE syntaxin from a closed
conformation to an open
conformation, which stimulates
the assembly of v-SNARE /t-SNARE
complexes.[28] RIM also appears
to regulate priming, but is not
essential for the step.

23. 5. Fusion
 Primed vesicles fuse very quickly in
response to calcium elevations in the
cytoplasm. This fusion event is thought to
be mediated directly by the SNAREs and
driven by the energy provided from
SNARE assembly. The calcium-sensing
trigger for this event is the calcium-
binding synaptic vesicle protein
synaptotagmin. The ability of SNAREs to
mediate fusion in a calcium-dependent
manner recently has been reconstituted
in vitro. Consistent with SNAREs being
essential for the fusion process, v-SNARE
and t-SNARE mutants of C. elegans are
lethal. Similarly, mutants in Drosophila and
knockouts in mice indicate that these
SNARES play a critical role in synaptic
exocytosis.[22]

24. 6. Exocytosis
"receptacle") is the durable, energy-
consuming process by which a cell
directs the contents of secretory
vesicles out of the cell membrane and
into the extracellular space. These
membrane-bound vesicles contain
soluble proteins to be secreted to the
extracellular environment, as well as
membrane proteins and lipids that are
sent to become components of the cell
membrane. However, the mechanism
of the secretion of intravesicular
contents out of the cell is very different
from the incorporation in the cell
membrane of ion channels, signaling
molecules, or receptors. (4)

25. Exocytosis – 2 / 2
While for membrane recycling and the
incorporation in the cell membrane of ion
channels, signaling molecules, or receptors
complete membrane merger is required, for
cell secretion there is transient vesicle fusion
with the porosome at the cell membrane in a
process called exocytosis, dumping its
contents out of the cell's environment.
Examination of cells following secretion using
electron microscopy, demonstrate increased
presence of partially empty vesicles following
secretion. This suggested that during the
secretory process, only a portion of the
vesicular content is able to exit the cell. This
could only be possible if the vesicle were to
temporarily establish continuity with the cell
plasma membrane, expel a portion of its
contents, then detach, reseal, and withdraw
into the cytosol (endocytose). In this way, the
secretory vesicle could be reused for
subsequent rounds of exo-endocytosis, until
completely empty of its contents.(4)

26. 7. Endocytosis
 This accounts for the re-uptake of
synaptic vesicles in the full contact
fusion model. However, other
studies have been compiling
evidence suggesting that this type
of fusion and endocytosis is not
always the case.

27. 8. Auto regulation

28.  Some neurotoxins, such as batrachotoxin, are known to destroy
synaptic vesicles. The tetanus toxin damages vesicle-associated
membrane proteins (VAMP), a type of v-SNARE, while botulinum
toxins damage t-SNARES and v-SNARES and thus inhibit synaptic
transmission.[20] A spider toxin called alpha-Latrotoxin binds to
neurexins, damaging vesicles and causing massive release of
neurotransmitters.

29. Vesicle Post-Synaptic behavior
 Kiss-and-Run
 Kiss-and-Stay
 Kiss-and-Go

30. kiss-and-run debate
 It has long been proposed that following vesicle fusion, a small pore
might open and close rapidly without full dilation. Such ‘kiss-and-run’
vesicle fusion can in principle result in rapid vesicle recycling and
influence the size and the kinetics of the resulting synaptic current.

31. kiss-and-run debate
 However, the existence of kiss-and-run remains highly controversial,
as revealed by recent imaging and electrophysiological studies at
several synapses, including hippocampal synapses, neuromuscular
junctions and retinal bipolar synapses.

32. kiss-and-run debate
 Only a minor fraction of fusion events has been shown to be kiss-
and-run, as determined using cell-attached capacitance
recordings in endocrine cells, pituitary nerve terminals and calyx-
type synapses.

33. kiss-and-run debate
 Further work is needed to determine whether kiss-and-run is a major
mode of fusion and has a major role in controlling synaptic strength
at synapses.

34. full collapse fusion
 More than three decades ago, full
collapse of the vesicle membrane
into the plasma membrane and
vesicle retrieval at a location distal
to the fusion site.
 This form of fusion is called ‘full
collapse fusion’.

35. kiss-and-run
 In addition, Ceccarelli and his co-
workers proposed that vesicle
fusion involves the opening of a
small pore, termed the ‘fusion
pore’, followed by its rapid closure
without full dilation and collapse
at the same site of fusion This
model, referred to as ‘kiss-and-run’
was based mainly on the electron
microscopic observation of the
uncoated omega membrane
profile with a narrow neck
connected to the plasma
membrane at the active zone of
the frog neuromuscular junction

36. full collapse fusion and kiss-and-run
 Switching between kiss-and-run and full collapse fusion might thus
provide a mechanism to regulate synaptic strength and achieve
synaptic plasticity.

37. Functional classification
{I’m going to design a Systematic Review, so you can join me by email:
hpf.javad@gmail.com}
Protein
Function
RIM
RIM-BP
Munch13
α-Liprin
ELKS
Others
AZ Structure Forming ! ! ! Piccolo, Bassoon, CASK, Mint
Tethering ! Rab3
Docking ! ! ! SNAP25, VAMP2, Syntaxin
Priming ! Synaptotagmin
37

38. References
1. (http://faculty.washington.edu/chudler/synapse.html)
2. Schacter, Daniel L.; Gilbert, Daniel T.; Wegner, Daniel M. (2011).
Psychology (2nd ed.). New York: Worth Publishers. p. 80
3. Silverthorn, Dee Unglaub (2007). Human Physiology: An Integrated
Approach. Illustration coordinator William C. Ober; illustrations by
Claire W. Garrison; clinical consultant Andrew C. Silverthorn;
contributions by Bruce R. Johnson (4th ed.). San Francisco:
Pearson/Benjamin Cummings. p. 271
4. Boron, WF & Boulpaep, EL (2012), Medical Physiology. A Cellular and
Molecular Approach 2, Philadelphia: Elsevier