The effect of Amyloid beta (Aβ) in neurotransmitter release

The aim of this project is to investigate the effects of Aβ on neuronal and synaptic physiology. Alzheimer’s Disease is strongly associated with Aβ deposits in the brain, and the soluble oligomeric forms of Aβ which correlate with cognitive decline. In certain brain regions, specifically the hippocampus, Aβ potently disrupts synaptic plasticity, by inhibiting the induction of LTP, and altering synaptic morphology. The mechanisms underlying this synaptic dysfunction remain largely unclear. Furthermore, the site of Aβ action remains elusive, with reports of toxic Aβ both internally and extracellularly, and evidence suggesting Aβ targets both the pre- and post-synapse. We have exciting data suggesting Aβ is interacting with presynaptic proteins affecting the regulation of SNARE complex formation allowing SV fusion and exocytosis.
The student will employ a range of techniques from culturing primary hippocampal neurons, to confocal microscopy, immuno labelling, treatment with Aβ etc. in order to investigate the effects induced by Aβ at the presynaptic contact. The project will investigate whether treatment of neurons with Aβ results in dissociation of presynaptic protein clusters.