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SUMMARY:Neuronal plasticity: from synapses to the axon initial segment - J
 uan Burrone\, Kings College London
DTSTART:20111028T151500Z
DTEND:20111028T170000Z
UID:TALK32577@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:We are interested in understanding how neurons wire up to form
  a stable network. Specifically\, we would like to know how synaptic conta
 cts between neurons form and mature during development. The transfer of in
 formation at mature synaptic contacts arises from the release of neurotran
 smitter from synaptic vesicles into the small confines of the synaptic cle
 ft and subsequent activation of post-synaptic receptors. However\, we know
  very little about the mechanisms of transmitter release during developmen
 t\, nor indeed when it is that synaptic transmission begins. We use cultur
 ed hippocampal neurons to study how axons and dendrites contact each other
  to form synapses and subsequently follow how these connections mature. A 
 number of different genetically-encoded probes were implemented to assess 
 the gradual maturation of both presynaptic and postsynaptic compartments. 
 Our results show that axons from young neurons (before synapses have forme
 d) display initially high levels of spontaneous vesicle cycling that are p
 rogressively down-regulated during synapse formation\, with a concomitant 
 increase in activity-dependent cycling as development proceeds. Interestin
 gly\, this early\, spontaneous release of neurotransmitter is sensed by di
 stant postsynaptic receptors\, resulting in spatially broad calcium signal
 s along a dendrite driven by NMDA receptors. We find that over 80% of thes
 e dendritic response sites did not co-localise with an axonal presynaptic 
 terminal suggesting that during neuronal development\, synaptic transmissi
 on can occur before contact is initiated. We are currently exploring the p
 ossible role that spontaneous release may have on driving local interactio
 ns between neurons as connections are established.\n\nWe are also particul
 arly interested in understanding how network activity remains stable durin
 g development\, a period that is highly plastic and characterised by rapid
  and large scale changes in connectivity. For this purpose\, neurons use h
 omeostatic forms of plasticity to control their excitability. Here\, we us
 ed an optotgenetic approach to precisely control the activity of individua
 l neurons in a network and study homeostatic plasticity at two crucial sit
 es for neuronal information processing and integration: the synapse and th
 e axon initial segment (AIS). We find that chronic changes in the activity
  of a single neuron results in compensatory\, cell-wide changes in synapti
 c gain. In parallel to this synaptic phenotype we find that the intrinsic 
 properties of neurons are also modulated: chronic increases in neuronal or
  network activity also cause a dramatic distal shift in AIS position along
  an axon. Since the AIS represents the site of action potential initiation
 \, we propose that movement of the AIS distally or proximally along the ax
 on may therefore represent a novel mechanism for controlling the intrinsic
  excitability of a neuron.\n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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