STRUCTURE AND FUNCTION OF THE SYNAPSE
Basic neuroscience
2013
What we are going to talk about?
“Chemical
synapses”
Postsynaptic
receptors
? (Metabotropic
Ionotropic
Receptors)
Postsynaptic
potential
EPSP (excitatory)
IPSP (inhibitory)
We will learn how neurons
comunicate with each other?
Nerve cells talking - and making sense
What’s the point?
•To understand how do we communicate to each other
•To understand the information transfer within the motor, sensory and
other systems such as higher brain functions, learning, aging,
sleeping etc.
• Average neuron forms and receives abut 1000
synaptic connections
• Human brain contains 10 neurons
11
• 10 synaptic connectins are formed in the
14
brain
Electrical vs chemical synapses
Synaptic cleft
Electrical synapse
• Ion channels connects presynaptic and
postsynaptic cell
• Current fllows directly from presyanptic to
postsynaptic neuron
• Lasts less than 0.1 msec
• Rectifying or unidirectionaly synapses
• Nonrectifying or bidirectional synapses (most
in the mammalian CNS)
Electrical synapse
Gap junction channels are
Formed by two hemichannels:
a) Presynaptic connexon
b) Postsynaptic connexon
Each connexon is composed of
Six subunits called connexins
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Chemical Synapse :
Functional synapse
connects two neurons:
There are three major
structures:
1. presynaptic element
2. synaptic cleft
3. postsynaptic element
Fig. 1.6.4. Axo-spinous synapse. The short spine of a thin type (S) originates from the dendritic stem (D).
Note obliquely sectioned thin parallel filaments in the postsynaptic density (so far unknown and
undescribed structure). Microtubule marked by arrow. Scale = 200 nm. (Mouse, neocortex.)
Synaptic transmission is:
• one way direction (unidirectional)
• fast (120 m/s)
• short-term ( 0,3 do1 ms)
• specific
• accurate
Double transmission of the signal
• 1. electrical signal becomes chemical
• 2. chemical signal transmits to:
– a) electrical (ionotropic-directly, metabotropic-indirectly)
– b) chemical (metabotropic receptors modulates activity of the ionic
channels))
Chemical synaptic transmission
• Involves five crucial steps:
1. Neurotransmitter synthesis
2. Storage
3. Release
4. Receptor binding
5. Inactivation
1. Biosynthesis of the neurotransmitter in the presynaptic
neuron
• Enzymes, cofactors and precursors are present
in presynaptic element
• It is important site for the clinically useful
drugs
2. Storage of the neurotransmitter in the presynaptic nerve
terminal
• When transmitters are stored in synaptic
vesicles they are protected from the enzymes
• Classical neurotransmitters (acetylcoline,
biogenic amines, and aminoacids such as
GABA, glutamate) are stored in small (≈50 nm
in diameter) vesicles
• Neuropeptide transmitters are stored in large
dense-core vesicles (≈100 nm in diameter)
Ahnert-Hilger G, Jahn R. CLC-3 spices up GABAergic synaptic vesicles. Nautre Neuroscience 2011:14;405-7, doi:10.1038/nn.2786
3. Release
• Calcium triggers release of transmitters
• Plasma membrane docking
• Membrane fusion (exocytosis)
• Endocytosis and recycling
From the following article:
The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission Maurizio Popoli, Zhen Yan,
Bruce S. McEwen & Gerard Sanacora. Nature Reviews Neuroscience 13, 22-37 (January 2012)
4. Receptor binding
• Released transmitter interacts with receptors
located on the target (postynaptic) cell.
• Receptors are:
a) Ionotropic (proteins that form ionic chanels)
b) Metabotropic (proteins that alter
intracellular process)
c) Autoreceptors (respond to transmitter
release from the neuron and modulate
transmitter release or synthesis)
B. Two major classes of receptors. 1. Ligand-Gated Ion Channels (Ionotropic) [Link]
GABA receptors
Dopamine receptors
Serotonin receptors
….except 5HT3 receptors
They are IONOTROPIC !!!!
Were can we find autoreceptors?
What happens when the transmitter binds to a specific site at
postsynaptic membrane ionotropic receptors?
•POSTSYNAPTIC POTENTIAL (PSP)?
What determines properties of PSP?
•PROPERTIES OF PSP (EITHER EXCITATORY-EPSP OR INHIBITORY-
IPSP) ARE DETERMINED BY THE NATURE OF GATING AND ION-
PENETRATION PROPERTIES OF SINGLE CHANNELS
Postsynaptic potentials
• EPSP – depolarizes cell membrane
• Increase the probability of cell firing
• IPSP – hyperpolarizes cell membrane
• Decrease the probability of cell firing
EPSP Action potential
• Na+ i K + travels • Na+ and K + travels
through the same ionic through selective
channel sodium and potassium
• Ionotropic receptor – channels
ligand gated channel
• Voltage gated channels
• Specific drugs and
natural toxins prevents • Selective toxins blocks
occurrence of EPSP occurrence of AP such
as tetrodotoxin (TTX)
Fig. 1.6.7. Two axo-dendritic synapses on a dendritic stem (D). The asymmetrical (Gray I) type with spherical
synaptic vesicles in the presynaptic bouton and prominent postsynaptic density (S, red asterisk) on the right, the
symmetrical (Gray II) type with pleiomorphic or flat vesicles in the presynaptic bouton and only slight
postsynaptic density (F, blue asterix on the left. Scale = 200 nm. (Rat, lateral geniculate nucleus.)
Excitatory postsynaptic potential
Inhibitory postsynaptic potential
• PATCH CLAMP METHOD– current flowing
through single isolated channel can be
measured directly, provides insight into both
the ionic mechanisms and molecular
properties of PSP mediated by ionotropic
receptors
• VOLTAGE CLAMP METHOD- keep the
membrane potential fixed during the flow of
synaptic current
REVERSAL POTENTIAL
• REVERSAL POTENTIAL– is the potential at
which given neurotransmitter causes no net
current flow of ions through that
neurotransmitter ion channel
EPSP
-ACh
-increases g(Na) i
g(K)
- Na current in cell
- K current out
-depolarisation
Vm= -65 mV
ENa= +55 mV
EK= - 75 mV
EEPSP= 0mV
IPSP
-GABA, glicin
-g(Cl-) increases
(ionotropic)
-g(K+) increases
(metabotropic)
-hyperpolarization
-Vm= -65 mV
-ECl= -70 mV
-EK= -80 mV
V. Central vs neuromuscular synapse
• Fig. 2: Basic shape of dendritic spine (left) compared to that of the neuromuscular junction (right).
The dendritic spine attaches to the dendrite with a narrow neck and receives a synapse on a bulb-
like head. This lollipop shape is similar to the shape of the interfolds sectioned transversely. Opened
axon terminal in green, synaptic vesicles in purple.
Central synapse vs Neuromuscular synapse
• cleft 15-20 nm • cleft 60-100 nm
• EPSP < 1 mV • EPSP has enchanced
• 3-10 AP = 1 synaptic amplitude
vesicles • 1 AP = 200 synaptic vesicles
• Several presynaptic AP = 1
postysnaptic AP • 1 presynaptic AP = 1
postsynaptic AP
• Higher concentration of
neurotransmitters – less • higher binding affinity (40%
binding affinity for Ach)
• Excitatory and inhibitory • Only excitatory synapses
• Different neurotransmitters • Only one neurotransmitter
• Numerous synapses on the (Ach)
same neuron
VII. Temporal and spatial summation
Inactivation of transmitters from the synaptic
cleft
• Difusion
• Enzyme degradation(acetylcholinesterase
hydrolyzes Ach)
• Reuptake mechanism (noradrenalin, dopamin,
serotonin, glutamate, GABA, glycin)
1. difusion
• Fig. 1. The glutamate–glutamine cycle in the brain. Glutamate released into the synaptic cleft acts on
postsynaptic receptors (NMDA and other types of glutamate receptors). Then glutamate is rapidly
removed from the synaptic cleft by glutamate transporters (e.g. EAAT1 and EAAT2) that are mainly located
on surrounding astrocytes. Within the astrocytes, glutamate and ammonia are combined to form
glutamine by glutamine synthetase (GS), an astrocyte-specific enzyme. To replenish the neurotransmitter
pool of glutamate, glutamine is released from astroyctes and taken up by glutamatergic neurons. Once
glutamine is taken up into the neuron, phosphate-activated glutamatetaminase (GLUTAMINEase) splits it
into glutamate and ammonia. Glutamate is then incorporated in synaptic vesicles that will release it to the
synaptic cleft, starting a new cycle.
• Courtesy of: Rodrigo and Felipo, Front. Biosci. 12, 883–890, Jan. 2007).
2. Enzymatic
inactivation
3. Reuptake
mechanism
Diseases of the synapses
• Myasthenia Gravis (affects nerve-muscle
synapse)
• Lambert-Eaton Syndrome (loss of voltage
gated calcium channels in the presyaptic
terminals
• Botulism
• Tetanus