The study of age-dependent changes in hippocampal synaptic function and network transmission in the triple transgenic Alzheimer's disease mouse model

Alzheimer’s disease (AD) is a neurodegenerative condition and a form of dementia. Initial cognitive impairment in early AD is due to dysfunction of hippocampal complex and intracellular Aβ plays major role. To study effect of Aβ on hippocampal complex, the triple-transgenic Alzheimer’s disease mouse model (3xTgAD) were used and measured by multi-electrode array that can detect whole hippocampus simultaneously with embedded 64 electrode channels. The I/O curve and change in short-term plasticity of three different pathways of hippocampal complex and effect of step by step increased application of CCh while elevating [K+] on frequency of Sharp-Wave like spontaneous activities were measured at three different ages on set (3-4, 6-7 and 7-8 month old) on both control and 3xTgAD then compared. The study revealed that age-dependent decrease in I/O curve in both control and 3xTgAD mice in local CA3 and CA1 pyramidal region and short term plasticity showed increased facilitation in local CA1 region of 3xTgAD. These results suggest that there may be a general decrease in SC (Schaffer collateral) connectivity during aging in both 3xTgAD and control mice. Furthermore, 3 month old 3xTgAD mice showed abnormally increased excitability in SC path, Challenging local CA3 pyramidal region of 3xTgAD mouse in vitro, with high voltage paired pulse successfully induced epileptiform activity (EA) in every hippocampal slices from 3month old 3xTgAD. In contrast, none of control mouse showed any sign of epileptic activity, suggesting 3month old 3xTgAD mouse indeed showed hyper-synaptic network excitability after exposed to hAβ chronically for relatively short period of time. However ability to evoke EA in 3xTgAD mice reduced to 50% by 6month of age then lost completely at 9month old, suggesting long-term exposure to Aβ abolishes initial excitatory effect. Finally, the CCh (Carbachol) induced EA experiment revealed slower transmission within regions of hippocampal complex network during EA and reduced efficacy towards CCh over ageing, ability to evoke EA in 3xTgAD mice reduced to 50% by 6month of age then lost almost completely at 9month old, suggesting long-term exposure to Aβ abolishes reduce ability to induce EA using CCh and slows down transmission of EA from initiated region to other regions of hippocampal complex.