Transcript ppt - IISER Pune

Synapse formation
Raghav Rajan
Bio 334 – Neurobiology I
September 5th 2013
5th September 2013
Bio 334 - Neurobiology I - Synapse and map formation
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Synapses are the connections between two neurons –
can be electrical or chemical
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Typical chemical
synapse
Presynaptic axon
Postsynaptic
dendrite
Synaptic cleft
Since they are small
– difficult to
visualize
Considerable
debate about their
presence
Bio 334 - Neurobiology I - Synapse and map formation
http://en.wikipedia.org/wiki/File:Active_zone3.JPG
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Synapses evolved about 1.1 million years ago, but
some components were present even earlier
5th September 2013
Bio 334 - Neurobiology I - Synapse and map formation
http://www.lscp.net/persons/ramus/fr/GDP1/papers/verhage00.pdf
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Complexity of the signalling process in the
postsynaptic density has increased greatly
5th September 2013
Bio 334 - Neurobiology I - Synapse and map formation
http://www.lscp.net/persons/ramus/fr/GDP1/papers/verhage00.pdf
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Synapse location and number are not random – instead
they are regulated
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Excitatory synapses
are typically on
spine heads
Inhibitory synapses
are typically on
cell bodies,
proximal dendrites
or spike necks
Synapse number
can vary depending
on target neurons
http://www.richardsmrt.com/?page_id=86
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Bio 334 - Neurobiology I - Synapse and map formation
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Three general observations related to synapse
formation
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Synaptic building blocks are manufactured by neurons
even before they make contacts with each other
Intercellular signaling, signals from glia, extracellular
matrix, neighbouring neurons – all participate in
synaptogenesis
Synapses mature over the course of development –
experience dependent plasticity, critical periods, etc....
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Bio 334 - Neurobiology I - Synapse and map formation
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Study of synapses gained speed in 1950s with the
advent of two new techniques
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Electron microscopy
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Intracellular recordings
http://faculty.washington.edu/chudler/java/em.html
http://en.wikipedia.org/wiki/File:RL_Squid_Synapse_2.jpg
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Bio 334 - Neurobiology I - Synapse and map formation
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Pre and post-synaptic membranes come close to each
other in a newly formed synapse
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But, not much can
be seen in terms
of presynaptic or
postsynaptic
specializations
Difficult to see
newly forming
synapses – since
there is nothing
much to see at
this stage
Bio 334 - Neurobiology I - Synapse and map formation
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 8
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A lot of information about synapse formation comes
from watching synapse formation in culture
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After contact,
filopodia retract
Slowly pre and
post-synaptic
parts mature
Extracellular
matrix also
matures
Bio 334 - Neurobiology I - Synapse and map formation
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 8
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Important features of synapses - location, location,
location – but how is this determined
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Inputs far away on
the dendritic tree
have less impact at
the cell body
Recent studies
show that this is
not entirely true –
may depend on the
properties of
dendrites in
different neurons
http://www.sciencedirect.com/science/article/pii/S0960982200000348?np=y
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Bio 334 - Neurobiology I - Synapse and map formation
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First synapses form on growth cones or extremities –
later on cell bodies
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Axo-dendritic synapses onto dendritic growth cones
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Axo-muscle synapses onto muscle myopodia
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May even be regulated by glia controlling accessibility to
various parts of the post-synaptic cell
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Bio 334 - Neurobiology I - Synapse and map formation
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Pre and post-synaptic structures can form independent
of partners
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Clustering of post-synaptic alpha-2 adrenergic receptors
without any presynaptic membrane in rat visual cortex
(p4)
Presynaptic terminal with vesicles in a Drosophila mutant
that does not make muscle
5th September 2013
Bio 334 - Neurobiology I - Synapse and map formation
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 8
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Synapse number increases after birth
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Cat visual cortex
Neuron density decreases
with increased gliogenesis
But neuronal processes
grow and start making
synapses
Bio 334 - Neurobiology I - Synapse and map formation
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 8
13
Growth cones of axons can release neurotransmitters
spontaneously before formation of contacts
5th September 2013
Bio 334 - Neurobiology I - Synapse and map formation
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 8
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Functional synapses can form very quickly in culture
soon after contact
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Muscle cell brought into
contact with neurite
Spontaneous currents and
evoked currents change
rapidly
Working synapse is produced
quickly
But, functional maturation
can take days to weeks
Bio 334 - Neurobiology I - Synapse and map formation
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 8
15
Stages in synapse formation – 1 – contact formation –
Ca2+, PKC, cAMP all play a role
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Contact with the correct
postsynaptic target can induce
a Ca2+ increase in the growth
cone triggering cytoskeletal
changes
Astrocytes also play a role in
this process
Bio 334 - Neurobiology I - Synapse and map formation
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 8
16
Stages in synapse formation – 2 – Increase in adhesion
between growth cone and target cell
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Increase in adhesion between
growth cone and target cell
within 15 minutes of contact
Nectins, cadherins, etc....
Bio 334 - Neurobiology I - Synapse and map formation
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 8
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Stages in synapse formation – 3 – converting sticky
growth cone to a presynaptic terminal
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Presynaptic terminals can
mature quickly without
concomitant maturation of
postsynaptic partners
Mature forms of either partner
can stimulate maturation of the
other
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous
System 2005 – Chapter 8
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Bio 334 - Neurobiology I - Synapse and map formation
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Signaling pathways again ..... they can change growth
cones into presynaptic terminals
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Different
signaling
pathways
activated by
contact
stimulate
change of
growth cone
into
presynaptic
terminal
Bio 334 - Neurobiology I - Synapse and map formation
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 8
19
Postsynaptic clustering of receptors can be
autonomous
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ACh receptors stained
with alpha-bungarotoxin
Mouse diaphragm muscle
Localization in the centre
even in mutants without
axon ingrowth
Stabilization by
presynaptic contact
Bio 334 - Neurobiology I - Synapse and map formation
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 8
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Postsynaptic clustering of receptors can also be
induced by contact with the right neurons
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Clustering can be induced by
contact
Bio 334 - Neurobiology I - Synapse and map formation
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 8
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Agrin, a proteoglycan, is another cluster-inducing
molecule
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In this case, basal lamina also
produce agrin and can induce
clustering of post-synaptic Ach
receptors (frog NMJ)
Agrin also produced by motor
neurons
Bio 334 - Neurobiology I - Synapse and map formation
Dan H Sanes, Thomas A Reh, William A Harris. Development of the Nervous System 2005 – Chapter 8
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Overall take home of synapse formation
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Highly specific in terms of location and connections
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Both sides play a role
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And there may be other players – glia, extracellular
matrix
The order of events is not completely understood – may
be different for different synapses
NOT FIXED – STILL ROOM FOR PLASTICITY
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Bio 334 - Neurobiology I - Synapse and map formation
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