Area-specific alterations of synaptic plasticity in the 5XFAD mouse model of Alzheimer's disease: dissociation between somatosensory cortex and hippocampus.
Transgenic mouse models of Alzheimer's disease (AD) that overproduce the amyloid beta peptide (Aβ) have highlighted impairments of hippocampal long-term synaptic plasticity associated with the progression of the disease. Here we examined whether the characteristics of one of the hallmarks of AD, i.e. Aβ deposition, in both the somatosensory cortex and the hippocampus, correlated with specific losses of synaptic plasticity in these areas. For this, we evaluated the occurrence of long-term potentiation (LTP) in the cortex and the hippocampus of 6-month old 5xFAD transgenic mice that exhibited massive Aβ deposition in both regions but with different features: in cortical areas a majority of Aβ deposits comprised a dense core surrounded by a diffuse corona while such kind of Aβ deposition was less frequently observed in the hippocampus. In order to simultaneously monitor synaptic changes in both areas, we developed a method based on the use of Multi-Electrode Arrays (MEA). When compared with wild-type (WT) mice, basal transmission was significantly reduced in both areas in 5xFAD mice, while short-term synaptic plasticity was unaffected. The induction of long-term changes of synaptic transmission by different protocols revealed that in 5xFAD mice, LTP in the layer 5 of the somatosensory cortex was more severely impaired than LTP triggered in the CA1 area of the hippocampus. We conclude that cortical plasticity is deficient in the 5xFAD model and that this deficit could be correlated with the proportion of diffuse plaques in 5xFAD mice.
Laboratory UMR7259 'Neurobiologie des Interactions Cellulaires et Neurophysiopathologie', Aix-Marseille University, Marseille, France ; Laboratory UMR7259 'Neurobiologie des Interactions Cellulaires et Neurophysiopathologie', CNRS, Marseille, France.
Nadine
N
Crouzin
Kevin
K
Baranger
Mélanie
M
Cavalier
Yannick
Y
Marchalant
Catherine
C
Cohen-Solal
François S
FS
Roman
Michel
M
Khrestchatisky
Santiago
S
Rivera
François
F
Féron
Michel
M
Vignes
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D058225:Plaque, Amyloid; D013003:Somatosensory Cortex / Q000473:pathology / Q000503:physiopathology*; D009435:Synaptic Transmission