QBI Seminar: The synaptic capture of membrane diffusing AMPA Receptors as a substrate for memory formation and disease.
Event Details
- Date:
- Monday, 01 September 2014 - Monday, 01 September 2014
- Time:
- 12:00 pm - 1:00 pm
- Room:
- Auditorium, Level 7
- UQ Location:
- Queensland Brain Institute (St Lucia)
- URL:
- http://www.qbi.uq.edu.au/neuroscience-seminars
- Event category(s):
Event Contact
- Name:
- Mr Reeza Nazer
- Phone:
- 66353
- Email:
- r.nazer@uq.edu.au
- Org. Unit:
- Queensland Brain Institute
Event Description
- Full Description:
- Speaker: Dr Patricio Opazo
Max Planck Institute for Neurobiology, Germany
Title: The synaptic capture of membrane diffusing AMPA Receptors as a substrate for memory formation and disease.
Abstract: It has long been postulated that memories are stored as a facilitation of excitatory synaptic transmission. On the other hand, neurodegenerative diseases that negatively impact memories such as Alzheimer's disease are believed to disrupt the very same mechanism of synaptic facilitation.
Given that AMPA Receptors (AMPAR) mediates most excitatory synaptic transmission, we investigated the molecular mechanisms leading to the synaptic capture and accumulation of AMPAR. In particular, we studied the synaptic recruitment of a large pool of mobile AMPAR present at the extrasynaptic surface. Using a combination of state-of-the-art imaging microscopy and electrophysiology, we demonstrated that mobile AMPAR can be synaptically immobilized via activation of the 'memory' molecule CaMKII. Mechanistically, we discovered that CaMKII trigger immobilization by phosphorylating the cytoplasmatic tail of Stargazin, an AMPAR auxiliary subunit.
Using a FRET-FLIM approach, we found that stargazin phosphorylation trigger a series of events such as membrane detachment, extension to the cytoplam and binding to the scaffold PSD95 to ultimately immobilize AMPAR and thus facilitate synaptic transmission. In recent studies, we have found that this diffusional trapping mechanism of AMPAR is perturbed in models of Alzheimer's Disease (AD) which lead to a aberrant AMPAR destabilization and ultimately to the loss of dendritic spines. In conclusion, our studies revealed that the diffusional trapping of AMPAR might be essential for the synaptic facilitation underlying memory and thus a potential target of memory impairing diseases such as AD.
Directions to UQ
- Google Map:
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- Directions:
- St Lucia Campus | Gatton campus.
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