Topic: A30P

Prodromal network hyperexcitability and mitochondrial dysfunction underly the pathogenesis of various forms of dementia. However, the role of hippocampal hyperexcitability and mitochondria in prodromal dementia with Lewy bodies (DLB) is unclear.We conducted multi-electrode array (MEA) recordings to investigate early hippocampal activity in a transgenic mouse model of DLB which harbours an alanine to proline point mutation (A30P) in the alpha synuclein gene (SNCA), causing overexpression. Hippocampal slices from young pre-symptomatic (2-4 months) male A30P (N = 6 slices/4 mice) and wild-type (W

Alpha-synuclein (ASYN) is a presynaptic neuronal protein related genetically and neuropathologically to Parkinson's disease (PD). However, the role of ASYN in the selective degeneration of specific neuronal populations such as the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) remains elusive. Since previous strategies for viral overexpression of ASYN in animals are not cell-type specific, we generated novel adeno-associated viral vectors (AAV) to Cre-dependently express human wild-type ASYN (ASYN-WT) or ASYN with pathogenic A53T or A30P mutations. This strategy allo