F. Tamagnini, C. Burattini, T. Casoli, M. Balietti, P. Fattoretti, G. Aicardi

Tg2576 is one of the most widely used mouse transgenic line in Alzheimer’s disease (AD) research. It carries a double missense mutation on the amyloid precursor protein gene (APP), resulting in marked increases in β-amyloid (Aβ) 1–40 and Aβ1–42 in the plasma and brain by 3–5 months of age, decrease in spine density in the outer molecular layer of the dentate gyrus at 4 months, decline in long-term potentiation of synaptic transmission in the dentate gyrus associated with impairment in contextual fear conditioning by 5 months, and plaque deposition in brain starting at 8 months. Visual recognition memory is seriously impaired in patients in the early stages of AD. The perirhinal cortex (Prh), a multimodal associative cortex of the temporal lobe, is critically involved in this form of memory; long-term depression of synaptic transmission (LTD) in this cortical region is regarded as its cellular correlate. The present work was aimed at evaluating if LTD in Prh of Tg2576 mice is already compromised at 3 months of age. Field excitatory post-synaptic potentials evoked by afferent pathways stimulation were recorded in layer II/III of Prh in horizontal brain slices obtained from 3 month old Tg2576 mice and littermate controls. We found that a single train of 3000 pulses delivered at 5 Hz induced LTD in slices from control mice, but not in those from Tg2576 mice. This result is consistent with the early visual recognition impairment observed in AD patients, and is particularly interesting because no changes in synaptic plasticity have previously been found so early in this transgenic line. Indeed, one of the major goals in AD research is to characterize the mechanisms leading to early functional impairments in order to improve diagnostic and therapeutic tools.

Keywords (Optional): 
Alzheimer’s disease
Tg2576 mice
perirhinal cortex
long-term depression
visual recognition memory