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Title: Exploring cell autonomous homeostatic plasticity at the synapse
Author: Humphreys, Lawrence
Awarding Body: King's College London (University of London)
Current Institution: King's College London (University of London)
Date of Award: 2012
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Homeostatic plasticity is thought to refer to the capacity of neurons to regulate their own excitability relative to network activity and occurs in a timescale of several days through modifications to ion channels and synaptic strength. Here, we present evidence showing that homeostatic plasticity is a cell autonomous phenomenon in that a single cell can modify its synaptic strength according to the activity that cell exhibits and not that of the network. This was accomplished using optogenetic tools. Moreover, we transfected single cells with Channelrhodopsin-2 allowing us to control the activity of these cells using light to excite and induce action potentials firing. In addition, we reduced the activity of the surrounding network by applying glutamatergic blockers. This allowed us to re-introduce normal levels of activity into the transfected cells using light, effectively rescuing them from the homeostatic effects induced by drug application. Immunohistochemical and electrophysiological evidence is provided showing that transfected neurons which exhibited normal levels of activity through photo stimulation did not undergo the synaptic homeostatic plasticity observed in the surrounding network. This strongly suggests that cells primarily regulate their homeostatic strength according to their own activity rather than that of the surrounding network. This however, does not exclude the possibility that the network does not have some effect on homeostatic plasticity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available