Synaptic excitability changes within the hippocampal formation of 3xTgAD mice

Abstract

Medial temporal lobe contains amygdala, entorhinal cortex and hippocampus with complex connections. The connections from basolateral amygdala nucleus to entorhinal cortex, as well as the entorhinal cortex to dentate gyrus were believed to play an important role in declarative memory. Alzheimer’s disease is the main disease which causes dementia. One of the most common symptoms of AD is the deficits in declarative memory. The post mortem studies found that medial temporal lobe is the main region showing the pathological changes. So far, 3 aspects of pathological changes including β-amyloid accumulation, hyperphosphorylated tau protein, as well as neuron loss were found in AD brain. Among those 3 changes, β-amyloid accumulation appeared earliest in the brain and was believed as a trigger of other pathological changes. The toxicity of intracellular β-amyloid in brain and cultured cell has been reported. But the relation between functional changes and intracellular β-amyloid accumulation is still unclear. In this project, both in vivo and in vitro electrophysiological technic were involved to find possible functional changes in the connection between BLP to EC, EC to DG in 3 and 6-month old 3xTgAD mice (with only intracellular β-Amyloid accumulation, absence of extracellular plaques and pTau caused neurofibrillary tangles). From the results, the connectivity was found decreasing in only 6-month 3xTg-AD mice. The paired-pulse index showed that late inhibition effects in 3xTgAD mice from both groups were lost. The late inhibition loss can be linked with dysfunction of GABAB receptors. In addition, the broader distribution of theta cycle intervals and power changing of theta and gamma oscillation from in vivo experiments were consistent with dysfunction of GABAB receptors. Those changes appear in the absence of extracellular plaques and pTau accumulation.

Date of Award	31 Dec 2019
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Jonathan Turner (Supervisor) & John Gigg (Supervisor)