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Summary NWI-BM001D - Molecular and Cellular Neurobiology
- Instelling
- Radboud Universiteit Nijmegen (RU)
Molecular and Cellular Neurobiology Abstract
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Molecular mechanism of neuronal communicationLecture 2 Introduction + ultrastructure of the mammalian synapse.
Synapse: Structures that mediate neuronal communication = Specialized cell-cell junction that
allows neurons to communicate with each other and non-neuronal target cells. So, can for
instance be muscle cells or glans or blood vessels.
You can discriminate between two types of synapses.
1. Chemical synapses: neurotransmitter-based (use neurotransmitters to communicate)
2. Electrical synapses: electrically coupled
Neural circuit: multiple neurons linked together by a set of synapses in series.
An important aspect to understand is the number of synapses in for instance a human central
nervous system and also the diversity.
- A typical neural in a mammalian brain: >10.000 synapses with other neurons.
- An adult human brain: estimated to contain >1014 synapses → human is capable of a lot.
In order to do so, you need a lot of neurons but also a lot of synapses. Not every synapse in the
brain equivalent.
Diversity of synapses based on the neurotransmitter that is used by the synapses:
- glutamate, GABA, glycine, dopamine, acetylcholine, (nor)epinephrine serotine, etc.
- co-transmission may occur → more than 1 neurotransmitter is used even in a single synapse.
(GABA + glycine)
Diversity of synapses based on the postsynaptic response that they induce:
- Excitatory synapses (e.g. glutamate): these synapses use an excitatory neurotransmitter.
And these neurotransmitters they induce postsynaptic depolarization. The presynaptic neuron
will secrete the excitatory neurotransmitter in this case, it will bind to its receptor (which is
located at the post synaptic side) and this receptor is an ion channel that is gated by the
neurotransmitter. So, it’s a ligand gated ion channel. So, if the neurotransmitter binds, the
channel will open and in the case of excitatory neurotransmitters and their receptors, there will
be an influx of positively charged ions (cat ions), and this will lead to depolarization of
postsynaptic cells.
- Inhibitory synapses (e.g. GABA, glycine): they use inhibitory neurotransmitters, and they
induce post synaptic hyperpolarization. And this is because the postsynaptic receptors that they
bind and activate are channels that conduct negatively charged ions (duct ions), and this induce
hyperpolarization of the postsynaptic cell. Therefore, it induced the generation of action
potential.
- Neuromodulatory synapses (e.g. dopamine, serotonin): these discriminate themselves
from excitatory and inhibitory synapses because the receptors for those neurotransmitters are
not ionotropic receptors (for example G Protein receptors), but rather they induce biochemical
changes in postsynaptic neuron.
Diversity of synapses based on their anatomical location.
- Central vs peripheral synapses. Synapses between neural in the cells in the CNS, vs the
synapses in the periphery meaning outside the CNS (e.g. neuro-muscular junctions, neuro-
endocrine junction, autonomous neuro-effector junction).
,1. Chemical synapses
Here, you can already see an overview of chemical neuronal communication. What you can see
here, is a schematic representation of a synapse with on the one hand a pre-synaptic neuron and
on the other hand a post-synaptic cell.
Post-synaptic cell: the post synaptic cells expresses receptors (red), which are clustered at the
synapse in the post synaptic density (PSD). So, those receptors will bind the neurotransmitter
that is secreted from the presynaptic nerve terminal. This will result in activation of the
receptor → the channel becomes open essentially for ions. This will result in the post-synaptic
response.
Pre-synaptic cell contains neurotransmitter. And this neurotransmitter is actually concentrated
in synaptic vesicles. These are organelles, that are membrane bound. Within the synaptic vesicle
there is the neurotransmitter that is automatically secreted by the pre-synaptic neurons.
How does this neurotransmitter get into the synaptic vesicle? The neurotransmitter is actually
pumped into the synaptic vesicle by neurotransmitter transporter (synaptic vesicle membrane
or membrane). Once the neurotransmitter is taken up. There will be a fraction of the synaptic
versicles that will be duct to what is called the active zone. And there are different steps that are
being distinguished. First you have the docking of the synaptic vesicle, then you have the
priming. And then you can get fusion of the synaptic vesicle with the pre-synaptic membrane.
This only happens when the pre-synaptic neuron is activated, which will result in the influx of
calcium.
What would happen is that if this pre-synaptic neuron is activated, it generates an action
potential. The action potential is conducted over the membrane of the neuron, and if will
therefore also arrive over the exon into the pre-synaptic exon terminal. And when it gets there,
it activated the voltage gated calcium channel. If there is a depolarization, these channels will
open. And there will be a local increase in the calcium concentration at the pre-synaptic side.
And this will trigger the exocytosis of the synaptic vesicle. Which will collapse into the pre-
synaptic membrane. And thereby release the neurotransmitter that they contain. Which will
defuse to the pos-synaptic membrane, bind and activate receptors there. Because these synaptic
vesicle collapses in the pre-synaptic membrane, the pre-synaptic membrane would enlarge in
size, however, not to long after the exocytosis, there will be endocytosis (for step of recycling of
synaptic vesicles).
,Ultrastructure of the mammalian synapse
Here you see a typical schematic representation of a synapse in the CNS, where you have pre-
synaptic nerve terminal that makes a synapse on the post-synaptic cell. In this case a post-
synaptic dendritic spine.
Mitochodrium (=generate ATP, to fuell processes)
Active zone
Post-synaptic
density (PSD)
neuron
Dendrite of a
A
B and F2 shown two electron microscopy images of a synapse. On electron microscopy you can
see electron dense structures. Here on B you see the membrane of such a pre-synaptic nerve
terminal. That contains synaptic vesicles (small round bolls with the clear center). Here you see
the dendritic spine. This is a typical synapse in the central nerve system.
Central synapse: where the axon of a presynaptic neuron contacts the dendrite of a postsynaptic
neuron. → There are two types of synapses based on the structure of the central synapse.
Type I = asymmetric synapse: excitatory; mainly on dendrites and dendrites spines. (A + B)
Type II = symmetric synapse: inhibitory; concentrate on cell soma and axonal initial segment.
F2 → Not on a dendritic spine. Arrow indicates the axon terminal with the synaptic vesicles with
the post synaptic density. But it is not in a dendritic spine. This might be either a cell body or an
axon.
Active zone = specialized region on the presynaptic plasma membrane, where synaptic vesicles
are docked and primed for release; the AZ is aligned with postsynaptic density (PSD).
→ Molecular composition of PSD: neurotransmitter receptors, transsynaptic adhesion
molecules, scaffolding molecules (bright the right protein together in the right place), signaling
molecules.
, What you see here is top left is a 3D structure of axons (white structures), and the red part of
the axon is where the synapse is located. So, in green you see the 3D reconstruction of a
dendrite, and this dendrite has so called boutons (3 enlargements). Boutons is where the axons
basically synapse on these dendrites. What you get now distinguishes it that boutons that have
more than one synaptic input (>1 axon synapse on the bouton) = multi synaptic boutons.
There are also boutons that only have a single axon that synapses = single synaptic boutons.
Or boutons that are being generated, or that used to be boutons = non-synaptic boutons
(because there is no synapse).
Mito: mitochondrion;
mvb: multivesicular body;
SSB: single synaptic bouton
(single postsynaptic partner);
NSB: nonsynaptic bouton (no
postsynaptic partner);
MSB: multisynaptic bouton (more
than one postsynaptic partner);
dcv: dense-core vesicle. vesicles
are yellow
A. Cerebellar Purkinje cell
dendrite; dendritic spines have
relatively uniform shape;
sp: spine.
B. Hippocampal CA1 dendrite
f: filopodia-like protrusion
st: stubby protrusion
m: mushroom-shaped spine
t: thin-shaped spine.
Red surfaces are PSD areas.
Synapses are plastic. That means that synapses, even in adults’ brain, continuously being
modified but also modulated and new synapses can be formed. Existing synapses can be lost.
Figure A: here you see a dendrite. And the red spots are dendritic spines. And in this case, you
can see that the dendritic spines are relatively uniform in shape. In compare to figure B. But
they are much more variation in their shape.
Question example: Which of the following are neuromodulatory neurotransmitters:
a. GABA = inhibitory neurotransmitter
b. glutamate = excitatory neurotransmitter
c. dopamine = neuromodulatory neurotransmitter
d. glycine = inhibitory neurotransmitter
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